By Kelly Shepard, PhD., CIRM’s Associate Director, Discovery & Translation
CIRM has previously blogged about advances in treating certain forms of “bubble baby” disease”, where a person is born with a defect in their blood forming stem cells that results in a deficient immune system, rendering them vulnerable to lethal infections by all manner of bacteria, virus or germ.
If a suitable donor can be found, or if the patient’s own defective cells can be corrected through gene therapy approaches, it is now possible to treat or cure such disorders through a bone marrow transplant. In this procedure, healthy blood stem cells are infused into the patient, taking up residence in his or her bone marrow and dividing to give rise to functioning immune cells such as T cells and B cells.
Unfortunately, there is another type of “bubble baby” disease that cannot be treated by providing healthy blood stem cells, because the defective immune system is caused by a different culprit altogether- a missing or dysfunctional thymus.
T Cells Go to School
What is a thymus? Most of us give little thought to this leaf-shaped organ, which is large and important in our early childhoods, but becomes small and inconspicuous as we age. This transformation belies the critical role a thymus plays in the development of our adaptive immune systems, which takes place in our youth: to prepare our bodies to fight infections for the rest of our lives.
One might think of the thymus as a “school”, where immature T cells go to “learn” how to recognize and attack foreign antigens (surface markers), such as those found on microorganisms or tissues from other individuals. The thymus also “teaches” our immune system to distinguish “self” from “other” by eliminating any T cells that attack our own tissues. Without this critical function, our immune system could inadvertently turn against us, causing serious autoimmune disorders such as ulcerative colitis and myasthenia gravis.
Many children with a severely deficient or absent thymus, referred to as athymia, have inherited a chromosome that is missing a key stretch of genes on a region called 22q11. Doctors believe perhaps 1/2000-1/4000 babies are born with some type of deletion in this region, which leads to a variable spectrum of disorders called 22q11 syndrome that can affect just about any part of the body, and can even cause learning disabilities and mental illness.
Individuals with one form of 22q11, called DiGeorge Syndrome, are particularly affected in the heart, thymus, and parathyroid glands. In the United States, about 20 infants are born per year with the “complete” and most severe form of DiGeorge Syndrome, who lack a thymus altogether, and have severely depressed numbers of T cells for fighting infections. Without medical intervention, this condition is usually fatal by 24 months of age.
Optimism and Setback
Although there are no therapies approved by the Food and Drug Administration (FDA) for pediatric athymia, Dr. Mary Louise Markert at Duke University and Enzyvant, Inc. have been pioneering an experimental approach to treat children with complete DiGeorge syndrome.
In this procedure, discarded thymic tissues are collected from infants undergoing cardiac surgery, where some of the thymus needs to be removed in order for the surgeon to gain access to the heart. These tissues are processed to remove potentially harmful donor T cells and then transplanted into the thigh of an athymic DiGeorge patient.
Results from early clinical trials seemed promising, with more than 70% of patients surviving, including several who are now ten years post-transplant. Based on those results, in June of 2019 Enzyvant applied to the FDA for a Biologics License Application (BLA), which is needed to be able to sell the therapy in the US. Unfortunately, only a few months later, Enzyvant announced that the FDA had declined to approve the BLA due to manufacturing concerns.
While it may be possible to address these issues in time, the need to step back to the drawing board was a devastating blow to the DiGeorge Community, who have waited decades for a promising treatment to emerge on the horizon.
Despite the setback, there is reason to hope. In early 2019, CIRM granted a “Quest” Award to team of investigators at Stanford University to develop a novel stem cell based approach for treating thymic deficiency. Co-led by Katja Weinacht, a pediatric hematologist/oncologist, and Vittorio Sebastiano, a stem cell expert and developmental biologist, the team’s strategy is to coax induced pluripotent stem cells (iPS) in the laboratory to differentiate into thymic tissue, which could then be transplanted into patients using the route pioneered by Duke and Enzyvant.
The beauty of this new approach is that pluripotent stem cells are essentially immortal in culture, providing an inexhaustible supply of fresh thymic cells for transplant, thereby allowing greater control over the quality and consistency of donor tissues. A second major advantage is the possibility of using pluripotent cells from the patient him/herself as the source, which should be perfectly immune-matched and alleviate the risk of rejection and autoimmunity that comes with use of donated tissues.
Sounds easy, so what are the challenges? As with many regenerative medicine approaches, the key is getting a pluripotent stem cell to differentiate into the right type of cells in the lab, which is a very different environment than what cells experience naturally when they develop in the context of an embryo and womb, where many cells are interacting and providing complex, instructive cues to one another. The precise factors and timing all need to be worked out and in most cases, this is done with an incomplete knowledge of human development.
A second challenge relates to using cells from DiGeorge patients to produce thymic tissue, which are missing several genes on their 22nd chromosome and will likely require sophisticated genetic engineering to restore this ability.
Fortunately, Drs. Weinacht and Sebastiano are up to the challenge, and have already made progress in differentiating human induced pluripotent stem cells (iPS) into thymic lineage intermediates that appear to be expressing the right proteins at the right time. They plan to combine these cells with engineered materials to create a three-dimensional (3D) tissue that more closely resembles an authentic organ, and which can be tested for functionality in athymic mice.
There is more work to be done, but these advances, along with continued technological improvements and renewed efforts from Enzyvant, could forge a path to the clinic and lead to a brighter future for patients suffering from congenital athymia and other forms of thymic dysfunction.
On December 12th we hosted our latest ‘Facebook Live: Ask the Stem Cell Team’ event. This time around we really did mean team. We had a host of our Science Officers answering questions from friends and supporters of CIRM. We got a lot of questions and didn’t have enough time to address them all. So here’s answers to all the questions.
What are the obstacles to using partial cellular reprogramming to return people’s entire bodies to a youthful state.Paul Hartman. San Leandro, California
Dr. Kelly Shepard: Certainly, scientists have observed that various manipulations of cells, including reprogramming, partial reprogramming, de-differentiation and trans-differentiation, can restore or change properties of cells, and in some cases, these changes can reflect a more “youthful” state, such as having longer telomeres, better proliferative capacity, etc. However, some of these same rejuvenating properties, outside of their normal context, could be harmful or deadly, for example if a cell began to grow and divide when or where it shouldn’t, similar to cancer. For this reason, I believe the biggest obstacles to making this approach a reality are twofold: 1) our current, limited understanding of the nature of partially reprogrammed cells; and 2) our inability to control the fate of those cells that have been partially reprogrammed, especially if they are inside a living organism. Despite the challenges, I think there will be step wise advances where these types of approaches will be applied, starting with specific tissues. For example, CIRM has recently funded an approach that uses reprogramming to make “rejuvenated” versions of T cells for fighting lung cancer. There is also a lot of interest in using such approaches to restore the reparative capacity of aged muscle. Perhaps some successes in these more limited areas will be the basis for expanding to a broader use.
What’s going on with Stanford’s stem cell trials for stroke? I remember the first trial went really well In 2016 have not heard anything about since? Elvis Arnold
Dr. Lila Collins: Hi Elvis, this is an evolving story. I believe you are referring to SanBio’s phase 1/2a stroke trial, for which Stanford was a site. This trial looked at the safety and feasibility of SanBio’s donor or allogeneic stem cell product in chronic stroke patients who still had motor deficits from their strokes, even after completing physical therapy when natural recovery has stabilized. As you note, some of the treated subjects had promising motor recoveries.
SanBio has since completed a larger, randomized phase 2b trial in stroke, and they have released the high-level results in a press release. While the trial did not meet its primary endpoint of improving motor deficits in chronic stroke, SanBio conducted a very similar randomized trial in patients with stable motor deficits from chronic traumatic brain injury (TBI). In this trial, SanBio saw positive results on motor recovery with their product. In fact, this product is planned to move towards a conditional approval in Japan and has achieved expedited regulatory status in the US, termed RMAT, in TBI which means it could be available more quickly to patients if all goes well. SanBio plans to continue to investigate their product in stroke, so I would stay tuned as the work unfolds.
Also, since you mentioned Stanford, I should note that Dr Gary Steinberg, who was a clinical investigator in the SanBio trial you mentioned, will soon be conducting a trial with a different product that he is developing, neural progenitor cells, in chronic stroke. The therapy looks promising in preclinical models and we are hopeful it will perform well for patients in the clinic.
I am a stroke survivor will stem cell treatment able to restore my motor skills?Ruperto
Dr. Lila Collins:
Hi Ruperto. Restoring motor loss after stroke is a very active area of research. I’ll touch upon a few ongoing stem cell trials. I’d just like to please advise that you watch my colleague’s comments on stem cell clinics (these can be found towards the end of the blog) to be sure that any clinical research in which you participate is as safe as possible and regulated by FDA.
Back to stroke, I mentioned SanBio’s ongoing work to address motor skill loss in chronic stroke earlier. UK based Reneuron is also conducting a phase 2 trial, using a neural progenitor cell as a candidate therapy to help recover persistent motor disability after stroke (chronic). Dr Gary Steinberg at Stanford is also planning to conduct a clinical trial of a human embryonic stem cell-derived neuronal progenitor cell in stroke.
There is also promising work being sponsored by Athersys in acute stroke. Athersys published results from their randomized, double blinded placebo controlled Ph2 trial of their Multistem product in patients who had suffered a stroke within 24-48 hours. After intravenous delivery, the cells improved a composite measure of stroke recovery, including motor recovery. Rather than acting directly on the brain, Multistem seems to work by traveling to the spleen and reducing the inflammatory response to a stroke that can make the injury worse.
Athersys is currently recruiting a phase 3 trial of its Multistem product in acute stroke (within 1.5 days of the stroke). The trial has an accelerated FDA designation, called RMAT and a special protocol assessment. This means that if the trial is conducted as planned and it reaches the results agreed to with the FDA, the therapy could be cleared for marketing. Results from this trial should be available in about two years.
Questions from several hemorrhagic stroke survivors who say most clinical trials are for people with ischemic strokes. Could stem cells help hemorrhagic stroke patients as well?
Dr. Lila Collins:
Regarding hemorrhagic stroke, you are correct the bulk of cell therapies for stroke target ischemic stroke, perhaps because this accounts for the vast bulk of strokes, about 85%.
That said, hemorrhagic strokes are not rare and tend to be more deadly. These strokes are caused by bleeding into or around the brain which damages neurons. They can even increase pressure in the skull causing further damage. Because of this the immediate steps treating these strokes are aimed at addressing the initial bleeding insult and the blood in the brain.
While most therapies in development target ischemic stroke, successful therapies developed to repair neuronal damage or even some day replace lost neurons, could be beneficial after hemorrhagic stroke as well.
I had an Ischemic stroke in 2014, and my vision was also affected. Can stem cells possibly help with my vision issues. James Russell
Dr. Lila Collins:
Hi James. Vision loss from stroke is complex and the type of loss depends upon where the stroke occurred (in the actual eye, the optic nerve or to the other parts of the brain controlling they eye or interpreting vision). The results could be:
Visual loss from damage to the retina
You could have a normal eye with damage to the area of the brain that controls the eye’s movement
You could have damage to the part of the brain that interprets vision.
You can see that to address these various issues, we’d need different cell replacement approaches to repair the retina or the parts of the brain that were damaged.
Replacing lost neurons is an active effort that at the moment is still in the research stages. As you can imagine, this is complex because the neurons have to make just the right connections to be useful.
Is there any stem cell therapy for optical nerve damage? Deanna Rice
Dr. Ingrid Caras: There is currently no proven stem cell therapy to treat optical nerve damage, even though there are shady stem cell clinics offering treatments. However, there are some encouraging early gene therapy studies in mice using a virus called AAV to deliver growth factors that trigger regeneration of the damaged nerve. These studies suggest that it may be possible to restore at least some visual function in people blinded by optic nerve damage from glaucoma
I read an article about ReNeuron’s retinitis pigmentosa clinical trial update. In the article, it states: “The company’s treatment is a subretinal injection of human retinal progenitors — cells which have almost fully developed into photoreceptors, the light-sensing retinal cells that make vision possible.” My question is: If they can inject hRPC, why not fully developed photoreceptors?Leonard
Dr. Kelly Shepard: There is evidence from other studies, including from other tissue types such as blood, pancreas, heart and liver, that fully developed (mature) cell types tend not to engraft as well upon transplantation, that is the cells do not establish themselves and survive long term in their new environment. In contrast, it has been observed that cells in a slightly less “mature” state, such as those in the progenitor stage, are much more likely to establish themselves in a tissue, and then differentiate into more mature cell types over time. This question gets at the crux of a key issue for many new therapies, i.e. what is the best cell type to use, and the best timing to use it.
My question for the “Ask the Stem Cell Team” event is: When will jCyte publish their Phase IIb clinical trial results. Chris Allen
Dr. Ingrid Caras: The results will be available sometime in 2020.
I understand the hRPC cells are primarily neurotropic (rescue/halt cell death); however, the literature also says hRPC can become new photoreceptors. My questions are:Approximately what percentage develop into functioning photoreceptors? And what percentage of the injected hRPC are currently surviving?Leonard Furber, an RP Patient
Dr. Kelly Shepard: While we can address these questions in the lab and in animal models, until there is a clinical trial, it is not possible to truly recreate the environment and stresses that the cells will undergo once they are transplanted into a human, into the site where they are expected to survive and function. Thus, the true answer to this question may not be known until after clinical trials are performed and the results can be evaluated. Even then, it is not always possible to monitor the fate of cells after transplantation without removing tissues to analyze (which may not be feasible), or without being able to transplant labeled cells that can be readily traced.
Dr. Ingrid Caras – Although the cells have been shown to be capable of developing into photoreceptors, we don’t know if this actually happens when the cells are injected into a patient’s eye. The data so far suggest that the cells work predominantly by secreting growth factors that rescue damaged retinal cells or even reverse the damage. So one possible outcome is that the cells slow or prevent further deterioration of vision. But an additional possibility is that damaged retinal cells that are still alive but are not functioning properly may become healthy and functional again which could result in an improvement in vision.
What advances have been made using stem cells for the treatment of Type 2 Diabetes?Mary Rizzo
Dr. Ross Okamura: Type 2 Diabetes (T2D) is a disease where the body is unable to maintain normal glucose levels due to either resistance to insulin-regulated control of blood sugar or insufficient insulin production from pancreatic beta cells. The onset of disease has been associated with lifestyle influenced factors including body mass, stress, sleep apnea and physical activity, but it also appears to have a genetic component based upon its higher prevalence in certain populations.
Type 1 Diabetes (T1D) differs from T2D in that in T1D patients the pancreatic beta cells have been destroyed by the body’s immune system and the requirement for insulin therapy is absolute upon disease onset rather than gradually developing over time as in many T2D cases. Currently the only curative approach to alleviate the heavy burden of disease management in T1D has been donor pancreas or islet transplantation. However, the supply of donor tissue is small relative to the number of diabetic patients. Donor islet and pancreas transplants also require immune suppressive drugs to prevent allogenic immune rejection and the use of these drugs carry additional health concerns. However, for some patients with T1D, especially those who may develop potentially fatal hypoglycemia, immune suppression is worth the risk.
To address the issue of supply, there has been significant activity in stem cell research to produce insulin secreting beta cells from pluripotent stem cells and recent clinical data from Viacyte’s CIRM funded trial indicates that implanted allogeneic human stem cell derived cells in T1D patients can produce circulating c-peptide, a biomarker for insulin. While the trial is not designed specifically to cure insulin-dependent T2D patients, the ability to produce and successfully engraft stem cell-derived beta cells would be able to help all insulin-dependent diabetic patients.
It’s also worth noting that there is a sound scientific reason to clinically test a patient-derived pluripotent stem cell-based insulin-producing cells in insulin-dependent T2D diabetic patients; the cells in this case could be evaluated for their ability to cure diabetes in the absence of needing to prevent both allogeneic and autoimmune responses.
SPINAL CORD INJURY
Is there any news on clinical trials for spinal cord injury? Le Ly
Kevin McCormack: The clinical trial CIRM was funding, with Asterias (now part of a bigger company called Lineage Cell Therapeutics, is now completed and the results were quite encouraging. In a news release from November of 2019 Brian Culley, CEO of Lineage Cell Therapeutics, described the results this way.
“We remain extremely excited about the potential for OPC1 (the name of the therapy used) to provide enhanced motor recovery to patients with spinal cord injuries. We are not aware of any other investigative therapy for SCI (spinal cord injury) which has reported as encouraging clinical outcomes as OPC1, particularly with continued improvement beyond 1 year. Overall gains in motor function for the population assessed to date have continued, with Year 2 assessments measuring the same or higher than at Year 1. For example, 5 out of 6 Cohort 2 patients have recovered two or more motor levels on at least one side as of their Year 2 visit whereas 4 of 6 patients in this group had recovered two motor levels as of their Year 1 visit. To put these improvements into perspective, a one motor level gain means the ability to move one’s arm, which contributes to the ability to feed and clothe oneself or lift and transfer oneself from a wheelchair. These are tremendously meaningful improvements to quality of life and independence. Just as importantly, the overall safety of OPC1 has remained excellent and has been maintained 2 years following administration, as measured by MRI’s in patients who have had their Year 2 follow-up visits to date. We look forward to providing further updates on clinical data from SCiStar as patients continue to come in for their scheduled follow up visits.”
Lineage Cell Therapeutics plans to meet with the FDA in 2020 to discuss possible next steps for this therapy.
In the meantime the only other clinical trial I know that is still recruiting is one run by a company called Neuralstem. Here is a link to information about that trial on the www.clinicaltrials.gov website.
Now that the Brainstorm ALS trial is finished looking for new patients do you have any idea how it’s going and when can we expect to see results? Angela Harrison Johnson
Dr. Ingrid Caras: The treated patients have to be followed for a period of time to assess how the therapy is working and then the data will need to be analyzed. So we will not expect to see the results probably for another year or two.
Are there treatments for autism or fragile x using stem cells? Magda Sedarous
Dr. Kelly Shepard: Autism and disorders on the autism spectrum represent a collection of many different disorders that share some common features, yet have different causes and manifestations, much of which we still do not understand. Knowing the origin of a disorder and how it affects cells and systems is the first step to developing new therapies. CIRM held a workshop on Autism in 2009 to brainstorm potential ways that stem cell research could have an impact. A major recommendation was to exploit stem cells and new technological advances to create cells and tissues, such as neurons, in the lab from autistic individuals that could then be studied in great detail. CIRM followed this recommendation and funded several early-stage awards to investigate the basis of autism, including Rett Syndrome, Fragile X, Timothy Syndrome, and other spectrum disorders. While these newer investigations have not yet led to therapies that can be tested in humans, this remains an active area of investigation. Outside of CIRM funding, we are aware of more mature studies exploring the effects of umbilical cord blood or other specific stem cell types in treating autism, such as an ongoing clinical trial conducted at Duke University.
What is happening with Parkinson’s research? Hanifa Gaphoor
Dr. Kent Fitzgerald: Parkinson’s disease certainly has a significant amount of ongoing work in the regenerative medicine and stem cell research.
The nature of cell loss in the brain, specifically the dopaminergic cells responsible for regulating the movement, has long been considered a good candidate for cell replacement therapy.
This is largely due to the hypothesis that restoring function to these cells would reverse Parkinson’s symptoms. This makes a lot of sense as front line therapy for the disease for many years has been dopamine replacement through L-dopa pills etc. Unfortunately, over time replacing dopamine through a pill loses its benefit, whereas replacing or fixing the cells themselves should be a more permanent fix.
Because a specific population of cells in one part of the brain are lost in the disease, multiple labs and clinicians have sought to replace or augment these cells by transplantation of “new” functional cells able to restore function to the area an theoretically restore voluntary motor control to patients with Parkinson’s disease.
Early clinical research showed some promise, however also yielded mixed results, using fetal tissue transplanted into the brains of Parkinson’s patients. As it turns out, the cell types required to restore movement and avoid side effects are somewhat nuanced. The field has moved away from fetal tissue and is currently pursuing the use of multiple stem cell types that are driven to what is believed to be the correct subtype of cell to repopulate the lost cells in the patient.
One project CIRM sponsored in this area with Jeanne Loring sought to develop a cell replacement therapy using stem cells from the patients themselves that have been reprogrammed into the kinds of cell damaged by Parkinson’s. This type of approach may ultimately avoid issues with the cells avoiding rejection by the immune system as can be seen with other types of transplants (i.e. liver, kidney, heart etc).
Still, others are using cutting edge gene therapy technology, like the clinical phase project CIRM is sponsoring with Krystof Bankiewicz to investigate the delivery of a gene (GDNF) to the brain that may help to restore the activity of neurons in the Parkinson’s brain that are no longer working as they should.
The bulk of the work in the field of PD at the present remains centered on replacing or restoring the dopamine producing population of cells in the brain that are affected in disease.
Any plans for Huntington’s?Nikhat Kuchiki
Dr. Lisa Kadyk: The good news is that there are now several new therapeutic approaches to Huntington’s Disease that are at various stages of preclinical and clinical development, including some that are CIRM funded. One CIRM-funded program led by Dr. Leslie Thompson at UC Irvine is developing a cell-based therapeutic that consists of neural stem cells that have been manufactured from embryonic stem cells. When these cells are injected into the brain of a mouse that has a Huntington’s Disease mutation, the cells engraft and begin to differentiate into new neurons. Improvements are seen in the behavioral and electrophysiological deficits in these mutant mice, suggesting that similar improvements might be seen in people with the disease. Currently, CIRM is funding Dr. Thompson and her team to carry out rigorous safety studies in animals using these cells, in preparation for submitting an application to the FDA to test the therapy in human patients in a clinical trial.
There are other, non-cell-based therapies also being tested in clinical trials now, using anti-sense oligonucleotides (Ionis, Takeda) to lower the expression of the Huntington protein. Another HTT-lowering approach is similar – but uses miRNAs to lower HTT levels (UniQure,Voyager)
TRAUMATIC BRAIN INJURY (TBI)
My 2.5 year old son recently suffered a hypoxic brain injury resulting in motor and speech disabilities. There are several clinical trials underway for TBI in adults. My questions are:
Will the results be scalable to pediatric use and how long do you think it would take before it is available to children?
I’m wondering why the current trials have chosen to go the route of intracranial injections as opposed to something slightly less invasive like an intrathecal injection?
Is there a time window period in which stem cells should be administered by, after which the administration is deemed not effective?
Dr. Kelly Shepard: TBI and other injuries of the nervous system are characterized by a lot of inflammation at the time of injury, which is thought to interfere with the healing process- and thus some approaches are intended to be delivered after that inflammation subsides. However, we are aware of approaches that intend to deliver a therapy to a chronic injury, or one that has occurred previously. Thus, the answer to this question may depend on how the intended therapy is supposed to work. For example, is the idea to grow new neurons, or is it to promote the survival of neurons of other cells that were spared by the injury? Is the therapy intended to address a specific symptom, such as seizures? Is the therapy intended to “fill a gap” left behind after inflammation subsides, which might not restore all function but might ameliorate certain symptoms.? There is still a lot we don’t understand about the brain and the highly sophisticated network of connections that cannot be reversed by only replacing neurons, or only reducing inflammation, etc. However, if trials are well designed, they should yield useful information even if the therapy is not as effective as hoped, and this information will pave the way to newer approaches and our technology and understanding evolves.
We have had a doctor recommending administering just the growth factors derived from MSC stem cells. Does the science work that way? Is it possible to isolate the growth factors and boost the endogenous growth factors by injecting allogenic growth factors?
Dr. Stephen Lin: Several groups have published studies on the therapeutic effects in non-human animal models of using nutrient media from MSC cultures that contain secreted factors, or extracellular vesicles from cells called exosomes that carry protein or nucleic acid factors. Scientifically it is possible to isolate the factors that are responsible for the therapeutic effect, although to date no specific factor or combination of factors have been identified to mimic the effects of the undefined mixtures in the media and exosomes. At present no regulatory approved clinical therapy has been developed using this approach.
PREDATORY STEM CELL CLINICS
What practical measures are being taken to address unethical practitioners whose bad surgeries are giving stem cell advances a bad reputation and are making forward research difficult?Kathy Jean Schultz
Dr. Geoff Lomax: Terrific question! I have been doing quite a bit research into the history of this issue of unethical practitioners and I found an 1842 reference to “quack medicines.” Clearly this is nothing new. In that day, the author appealed to make society “acquainted with the facts.”
In California, we have taken steps to (1) acquaint patients with the facts about stem cell treatments and (2) advance FDA authorized treatments for unmet medical needs.
First, CIRM work with Senator Hernandez in 2017 to write a law the requires provides to disclose to patient that a stem cell therapy has not been approved by the Food and Drug administration.
We continue to work with the State Legislature and Medical Board of California to build on policies that require accurate disclosure of the facts to patients.
Second, our clinical trial network the — Alpha Stem Cell Clinics – have supported over 100 FDA-authorized clinical trials to advance responsible clinical research for unmet medical needs.
I’m curious if adipose stem cell being used at clinics at various places in the country is helpful or beneficial?Cheri Hicks
Adipose tissue has been widely used particularly in plastic and reconstructive surgery. Many practitioners suggest adipose cells are beneficial in this context. With regard to regenerative medicine and / or the ability to treat disease and injury, I am not aware of any large randomized clinical trials that demonstrate the safety and efficacy of adipose-derived stem cells used in accordance with FDA guidelines.
I went to a “Luncheon about Stem Cell Injections”. It sounded promising. I went thru with it and got the injections because I was desperate from my knee pain. The price of stem cell injections was $3500 per knee injection. All went well. I have had no complications, but haven’t noticed any real major improvement, and here I am a year later. My questions are:
1) I wonder on where the typical injection cells are coming from?
2) I wonder what is the actual cost of the cells?
3) What kind of results are people getting from all these “pop up” clinics or established clinics that are adding this to there list of offerings?
Dr. Geoff Lomax: You raise a number of questions and point here; they are all very good and it’s is hard to give a comprehensive response to each one, but here is my reaction:
There are many practitioners in the field of orthopedics who sincerely believe in the potential of cell-based treatments to treat injury / pain
Most of the evidence presented is case reports that individuals have benefited
The challenge we face is not know the exact type of injury and cell treatments used.
Well controlled clinical trials would really help us understand for what cells (or cell products) and for what injury would be helpful
Prices of $3000 to $5000 are not uncommon, and like other forms of private medicine there is often a considerable mark-up in relation to cost of goods.
You are correct that there have not been reports of serious injury for knee injections
However the effectiveness is not clear while simultaneously millions of people have been aided by knee replacements.
Do stem cells have benefits for patients going through chemotherapy and radiation therapy?Ruperto
Dr. Kelly Shepard: The idea that a stem cell therapy could help address effects of chemotherapy or radiation is being and has been pursued by several investigators over the years, including some with CIRM support. Towards the earlier stages, people are looking at the ability of different stem cell-derived neural cell preparations to replace or restore function of certain brain cells that are damaged by the effects of chemotherapy or radiation. In a completely different type of approach, a group at City of Hope is exploring whether a bone marrow transplant with specially modified stem cells can provide a protective effect against the chemotherapy that is used to treat a form of brain cancer, glioblastoma. This study is in the final stage of development that, if all goes well, culminates with application to the FDA to allow initiation of a clinical trial to test in people.
Dr. Ingrid Caras: That’s an interesting and valid question. There is a Phase 1 trial ongoing that is evaluating a novel type of stem/progenitor cell from the umbilical cord of healthy deliveries. In animal studies, these cells have been shown to reduce the toxic effects of chemotherapy and radiation and to speed up recovery. These cells are now being tested in a First-in-human clinical trial in patients who are undergoing high-dose chemotherapy to treat their disease.
There is a researcher at Stanford, Michelle Monje, who is investigating that the role of damage to stem cells in the cognitive problems that sometimes arise after chemo- and radiation therapy (“chemobrain”). It appears that damage to stem cells in the brain, especially those responsible for producing oligodendrocytes, contributes to chemobrain. In CIRM-funded work, Dr. Monje has identified small molecules that may help prevent or ameliorate the symptoms of chemobrain.
Is it possible to use a technique developed to fight one disease to also fight another? For instance, the bubble baby disease, which has cured (I think) more than 50 children, may also help fight sickle cell anemia? Don Reed.
Dr. Lisa Kadyk: Hi Don. Yes, the same general technique can often be applied to more than one disease, although it needs to be “customized” for each disease. In the example you cite, the technique is an “autologous gene-modified bone marrow transplant” – meaning the cells come from the patient themselves. This technique is relevant for single gene mutations that cause diseases of the blood (hematopoietic) system. For example, in the case of “bubble baby” diseases, a single mutation can cause failure of immune cell development, leaving the child unable to fight infections, hence the need to have them live in a sterile “bubble”. To cure that disease, blood stem cells, which normally reside in the bone marrow, are collected from the patient and then a normal version of the defective gene is introduced into the cells, where it is incorporated into the chromosomes. Then, the corrected stem cells are transplanted back into the patient’s body, where they can repopulate the blood system with cells expressing the normal copy of the gene, thus curing the disease.
A similar approach could be used to treat sickle cell disease, since it is also caused by a single gene mutation in a gene (beta hemoglobin) that is expressed in blood cells. The same technique would be used as I described for bubble baby disease but would differ in the gene that is introduced into the patient’s blood stem cells.
Is there any concern that CIRM’s lack of support in basic research will hamper the amount of new approaches that can reach clinical stages? Jason
Dr. Kelly Shepard: CIRM always has and continues to believe that basic research is vital to the field of regenerative medicine. Over the past 10 years CIRM has invested $904 million in “discovery stage/basic research”, and about $215 million in training grants that supported graduate students, post docs, clinical fellows, undergraduate, masters and high school students performing basic stem cell research. In the past couple of years, with only a limited amount of funds remaining, CIRM made a decision to invest most of the remaining funds into later stage projects, to support them through the difficult transition from bench to bedside. However, even now, CIRM continues to sponsor some basic research through its Bridges and SPARK Training Grant programs, where undergraduate, masters and even high school students are conducting stem cell research in world class stem cell laboratories, many of which are the same laboratories that were supported through CIRM basic research grants over the past 10 years. While basic stem cell research continues to receive a substantial level of support from the NIH ($1.8 billion in 2018, comprehensively on stem cell projects) and other funders, CIRM believes continued support for basic research, especially in key areas of stem cell research and vital opportunities, will always be important for discovering and developing new treatments.
What is the future of the use of crispr cas9 in clinical trials in california/globally. Art Venegas
Dr. Kelly Shepard: CRISPR/Cas9 is a powerful gene editing tool. In only a few years, CRISPR/Cas9 technology has taken the field by storm and there are already a few CRISPR/Cas9 based treatments being tested in clinical trials in the US. There are also several new treatments that are at the IND enabling stage of development, which is the final testing stage required by the FDA before a clinical trial can begin. Most of these clinical trials involving CRISPR go through an “ex vivo” approach, taking cells from the patient with a disease causing gene, correcting the gene in the laboratory using CRISPR, and reintroducing the cells carrying the corrected gene back into the patient for treatment. Sickle cell disease is a prime example of a therapy being developed using this strategy and CIRM funds two projects that are preparing for clinical trials with this approach. CRISPR is also being used to develop the next generation of cancer T-cell therapies (e.g. CAR-T), where T-cells – a vital part of our immune system – are modified to target and destroy cancer cell populations. Using CRISPR to edit cells directly in patients “in vivo” (inside the body) is far less common currently but is also being developed. It is important to note that any FDA sanctioned “in vivo” CRISPR clinical trial in people will only modify organ-specific cells where the benefits cannot be passed on to subsequent generations. There is a ban on funding for what are called germ line cells, where any changes could be passed down to future generations.
CIRM is currently supporting multiple CRISPR/Cas9 gene editing projects in California from the discovery or most basic stage of research, through the later stages before applying to test the technique in people in a clinical trial.
While the field is new – if early safety signals from the pioneering trials are good, we might expect a number of new CRISPR-based approaches to enter clinical testing over the next few years. The first of these will will likely be in the areas of bone marrow transplant to correct certain blood/immune or metabolic diseases, and cancer immunotherapies, as these types of approaches are the best studied and furthest along in the pipeline.
Explain the differences between gene therapy and stem cell therapy?Renee Konkol
Dr. Stephen Lin: Gene therapy is the direct modification of cells in a patient to treat a disease. Most gene therapies use modified, harmless viruses to deliver the gene into the patient. Gene therapy has recently seen many success in the clinic, with the first FDA approved therapy for a gene induced form of blindness in 2017 and other approvals for genetic forms of smooth muscle atrophy and amyloidosis.
Stem cell therapy is the introduction of stem cells into patients to treat a disease, usually with the purpose of replacing damaged or defective cells that contribute to the disease. Stem cell therapies can be derived from pluripotent cells that have the potential to turn into any cell in the body and are directed towards a specific organ lineage for the therapy. Stem cell therapies can also be derived from other cells, called progenitors, that have the ability to turn into a limited number of other cells in the body. for example hematopoietic or blood stem cells (HSCs), which are found in bone marrow, can turn into other cells of the blood system including B-cells and T-cells: while mesenchymal stem cells (MSCs), which are usually found in fat tissue, can turn into bone, cartilage, and fat cells. The source of these cells can be from the patient’s own body (autologous) or from another person (allogeneic).
Gene therapy is often used in combination with cell therapies when cells are taken from the patient and, in the lab, modified genetically to correct the mutation or to insert a correct form of the defective gene, before being returned to patients. Often referred to as “ex vivo gene therapy” – because the changes are made outside the patient’s body – these therapies include Chimeric Antigen Receptor T (CAR-T) cells for cancer therapy and gene modified HSCs to treat blood disorders such as severe combined immunodeficiency and sickle cell disease. This is an exciting area that has significantly improved and even cured many people already.
Currently, how can the outcome of CIRM stem cell medicine projects and clinical trials be soundly interpreted when their stem cell-specific doses are not known?James L. Sherley, M.D., Ph.D., Director. Asymmetrex, LLC
Dr. Stephen Lin: Stem cell therapies that receive approval to conduct clinical trials must submit a package of data to the FDA that includes studies that demonstrate their effectiveness, usually in animal models of the disease that the cell therapy is targeting. Those studies have data on the dose of the cell therapy that creates the therapeutic effect, which is used to estimate cell doses for the clinical trial. CIRM funds discovery and translational stage awards to conduct these types of studies to prepare cell therapies for clinical trials. The clinical trial is also often designed to test multiple doses of the cell therapy to determine the one that has the best therapeutic effect. Dosing can be very challenging with cell therapies because of issues including survival, engraftment, and immune rejection, but CIRM supports studies designed to provide data to give the best estimate possible.
Is there any research on using stem cells to increase the length of long bones in people?” For example, injecting stem cells into the growth plates to see if the cells can be used to lengthen limbs.Sajid
Dr. Kelly Shepard: There is quite a lot of ongoing research seeking ways to repair bones with stem cell based approaches, which is not the same but somewhat related. Much of this is geared towards repairing the types of bone injuries that do not heal well naturally on their own (large gaps, dead bone lesions, degenerative bone conditions). Also, a lot of this research involves engineering bone tissues in the lab and introducing the engineered tissue into a bone lesion that need be repaired. What occurs naturally at the growth plate is a complex interaction between many different cell types, much of which we do not fully understand. We do not fully understand how to use the cells that are used to engineer bone tissue in the lab. However, a group at Stanford, with some CIRM support, recently discovered a “skeletal stem cell” that exists naturally at the ends of human bones and at sites of fracture. These are quite different than MSCs and offer a new path to be explored for repairing and generating bone.
On the surface, actor Michael J. Fox, singer Neil Diamond, civil rights activist Jesse Jackson and Scottish comedian Billy Connolly would appear to have little in common. Except for one thing. They all have Parkinson’s Disease (PD).
Their celebrity status has helped raise public awareness about the condition, but studies show that awareness doesn’t amount to an understanding of PD or the extent to which it impacts someone’s life. In fact a study in the UK found that many people still don’t think PD is a serious condition.
To try and help change that people around the world will be
holding events today, April 11th, World Parkinson’s Day.
The disease was first described by James Parkinson in 1817 in “An Essay on the Shaking Palsy”. In the essay Parkinson described a pattern of trembling in the hands and fingers, slower movement and loss of balance. Our knowledge about the disease has advanced in the last 200 years and now there are treatments that can help slow down the progression of the disease. But those treatments only last for a while, and so there is a real need for new treatments.
That’s what Jun Takahashi’s team at Kyoto University in
Japan hope to provide. In a first-of-its-kind procedure they took skin cells
from a healthy donor and reprogrammed them to become induced pluripotent stem
cells (iPSCs), or stem cells that become any type of cell. These iPSCs were
then turned into the precursors of dopamine-producing neurons, the cells
destroyed by PD, and implanted into 12 brain regions known to be hotspots for
was carried out in October and the patient, a male in his 50s, is still
healthy. If his symptoms continue to improve and he doesn’t experience any bad
side effects, he will receive a second dose of dopamine-producing stem
cells. Six other patients are scheduled to receive this same treatment.
Earlier tests in monkeys showed that the implanted stem cells improved Parkinson’s symptoms without causing any serious side effects.
Scientists at UC San
Francisco are trying a different approach, using gene therapy to tackle one of
the most widely recognized symptoms of PD, muscle movement.
In the study,
published in the journal Annals
of Neurology, the team used
an inactive virus to deliver a gene to boost production of dopamine in the
brain. In a Phase 1 clinical trial 15 patients, whose medication was no longer
able to fully control their movement disorder, were treated with this approach.
Not only were they able to reduce their medication – up to 42 percent in some
cases – the medication they did take lasted longer before causing dyskinesia,
an involuntary muscle movement that is a common side effect of the PD
In a news article Dr. Chad Christine, the first author of the
study, says this approach may also help reduce other symptoms.
“Since many patients were able to substantially
reduce the amount of Parkinson’s medications, this gene therapy treatment may
also help patients by reducing dose-dependent side effects, such as sleepiness
At CIRM we have
a long history of funding research into PD. Over the years we have invested
more than $55 million to try and develop new treatments for the disease.
In June 2018, the CIRM Board awarded $5.8 million to UC San Francisco’s Krystof Bankiewicz and Cedars-Sinai’s Clive Svendsen. They are using neural progenitor cells, which have the ability to multiply and turn into other kinds of brain cells, and engineering them to express the growth factor GDNF which is known to protect the cells damaged in PD. The hope is that when transplanted into the brain of someone with PD, it will help slow down, or even halt the progression of the disease.
The CIRM funding
will hopefully help the team do the pre-clinical research needed to get the
FDA’s go-ahead to test this approach in a clinical trial.
At the time of the award David Higgins, PhD, the CIRM Board Patient Advocate for Parkinson’s Disease, said: “One of the big frustrations for people with Parkinson’s, and their families and loved ones, is that existing therapies only address the symptoms and do little to slow down or even reverse the progress of the disease. That’s why it’s important to support any project that has the potential to address Parkinson’s at a much deeper, longer-lasting level.”
But we don’t just fund the research, we try to bring the scientific community together to help identify obstacles and overcome them. In March of 2013, in collaboration with the Center for Regenerative Medicine (CRM) of the National Institutes of Health (NIH), we held a two-day workshop on cell therapies for Parkinson’s Disease. The experts outlined the steps needed to help bring the most promising research to patients.
Around one million Americans are currently living with Parkinson’s Disease. Worldwide the number is more than ten million. Those numbers are only expected to increase as the population ages. There is clearly a huge need to develop new treatments and, hopefully one day, a cure.
Till then days like April 11th will be an
opportunity to remind ourselves why this work is so important.
For some years now CIRM has been raising the alarm about the growing numbers of clinics offering unproven and unapproved stem cell therapies. But we are not alone. Now a leader of the California state Assembly is taking action, trying to ensure the clinics follow the law and don’t endanger patients.
Kevin Mullin is the Speaker pro Tem in the Assembly. He is championing a bill, AB 617, that will create a Stem Cell Clinic Regulation Advisory Group. In a news release Mullin said the motivation behind the bill is simple:
“As the Chair of the Select Committee on Biotechnology, I have heard from patients who have experienced both sides of the treatment continuum. It is clear that more must be done to ensure the proper regulation of for-profit stem cell clinics.”
Concerns about these clinics are well-founded. The clinics claim the treatments they offer – usually involving the use of the patient’s own fat or blood cells – can help address everything from arthritis to Alzheimer’s but offer little or no proof. Because the “therapies” are not approved by the FDA they are not covered by insurance, so people spend thousands, sometimes tens of thousands of dollars for something that is almost guaranteed to do little to help. In some cases, the “treatments” have had disastrous results, harming patients.
The news release
from Speaker pro Tem Mullin’s office says CIRM has helped position California
as a leader in stem cell research.
not all stem cell clinics are adhering to the expected high standards of review
within the industry and, as a result, patients have been subjected to
unscrupulous, sometimes harmful practices. AB 617 will address those entities
by creating a Stem Cell Clinic Regulation Advisory Group.”
The Advisory Group will review existing licensing and certification laws for clinics offering stem cell therapies. The Group would then make recommendations to the Legislature about ways to improve the existing rules and ensure greater protection for patients. CIRM has been working with Speaker pro Tem Mullin on AB 617 and, as our President & CEO, Maria Millan, said we will continue to do so.
“We fully support AB 617
and Speaker pro Tem Mullin’s efforts to protect California consumers from
unregulated and unproven stem cell treatments. AB 617 will help
patients, their families and the medical community identify legitimate clinics
that offer scientifically tested clinical trials and treatments that meet
federal regulatory requirements. The field of regenerative medicine
and cell and gene therapy are coming of age and entering the realm of medical
practice, so AB 617 would set up an important foundation for ensuring that the
highest quality care is provided to patients seeking these treatments.”
Last week’s news headlines were dominated by one big story, the use of a stem cell transplant to effectively cure a person of HIV. But there were other stories that, while not quite as striking, did also highlight how the field is advancing.
A new way to boost brain cells
It’s hard to fix
something if you don’t really know what’s wrong in the first place. It would be
like trying to determine why a car is not working just by looking at the hood
and not looking inside at the engine. The human brain is far more complex than
a car so trying to determine what’s going wrong is infinitely more challenging.
But a new study could help give us a new option.
Luxembourg and Germany have developed a new computer model for what’s happening
inside the brain, identifying what cells are not operating properly, and fixing
Antonio del Sol, one
of the lead authors of the study – published in the journal Cell
– says their new model allows them to identify which stem cells are active and
ready to divide, or dormant.
“Our results constitute an important
step towards the implementation of stem cell-based therapies, for instance for
neurodegenerative diseases. We were able to show that, with computational
models, it is possible to identify the essential features that are
characteristic of a specific state of stem cells.”
The work, done in
mice, identified a protein that helped keep brain stem cells inactive in older
animals. By blocking this protein they were able to help “wake up” those stem
cells so they could divide and proliferate and help regenerate the aging brain.
And if it works in
mice it must work in people right? Well, that’s what they hope to see next.
Deeper understanding of fetal development
According to the Mayo
Clinic between 10 and 20 percent of known pregnancies end in
miscarriage (though they admit the real number may be even higher) and our lack
of understanding of fetal development makes it hard to understand why. A new
study reveals a previously unknown step in this development that could help
provide some answers and, hopefully, lead to ways to prevent miscarriages.
Researchers at the
Karolinska Institute in Sweden used genetic sequencing to follow the
development stages of mice embryos. By sorting those different sequences into a
kind of blueprint for what’s happening at every stage of development they were
able to identify a previously unknown phase. It’s the time between when the
embryo attaches to the uterus and when it begins to turn these embryonic stem
cells into identifiable parts of the body.
Lead researcher Qiaolin Deng says this finding provides vital new evidence.
“Being able to follow the
differentiation process of every cell is the Holy Grail of developmental
biology. Knowledge of the events and factors that govern the development of the
early embryo is indispensable for understanding miscarriages and congenital
disease. Around three in every 100 babies are born with fetal malformation
caused by faulty cellular differentiation.”
Could a new drug discovery
reduce damage from a heart attack?
Every 40 seconds someone in the US has a heart attack. For many it is fatal but even for those who survive it can lead to long-term damage to the heart that ultimately leads to heart failure. Now British researchers think they may have found a way to reduce that likelihood.
Using stem cells to
create human heart muscle tissue in the lab, they identified a protein that is
activated after a heart attack or when exposed to stress chemicals. They then
identified a drug that can block that protein and, when tested in mice that had
experienced a heart attack, they found it could reduce damage to the heart
muscle by around 60 percent.
Prof Michael Schneider,
the lead researcher on the study, published in Cell
Stem Cell, said this could be a game changer.
“There are no
existing therapies that directly address the problem of muscle cell death and
this would be a revolution in the treatment of heart attacks. One reason why
many heart drugs have failed in clinical trials may be that they have not been
tested in human cells before the clinic. Using both human cells and animals
allows us to be more confident about the molecules we take forward.”
You never know when you write something if people are going to read it. Sometimes you wonder if anyone is going to read it. So, it’s always fun, and educational, to look back at the end of the year and see which pieces got the most eyeballs.
It isn’t always the ones you think will draw the biggest audiences. Sometimes it is diseases that are considered “rare” (those affecting fewer than 200,000 people) that get the most attention.
Maybe it’s because those diseases have such a powerful online community which shares news, any news, about their condition of interest with everyone they know. Whatever the reason, we are always delighted to share encouraging news about research we are funding or encouraging research that someone else is funding.
That was certainly the case with the top two stories this year. Both were related to ALS or Lou Gehrig’s disease. It’s a particularly nasty condition. People diagnosed with ALS have a life expectancy of just 2 to 5 years. So it’s probably not a big surprise that stories suggesting stem cells could expand that life span got a big reception.
Whatever the reason, we’re just happy to share hopeful news with everyone who comes to our blog.
And so, without further ado, here is the list of the most popular Stem Cellar Blog Posts for 2018.
All of us in the Communications team at CIRM consider it an honor and privilege to be able to work here and to meet many of the people behind these stories; the researchers and the patients and patient advocates. They are an extraordinary group of individuals who help remind us why we do this work and why it is important. We love our work and we hope you enjoy it too. We plan to be every bit as active and engaged in 2019.
As we get older things that used to heal quickly tend to take a little longer to get better. In some cases, a lot longer. Take bones for example. A fracture in someone who is in their 70’s often doesn’t heal as quickly, or completely, as in someone much younger. For years researchers have been working on ways to change that. Now we may be one step closer to doing just that.
We know that using blood stem cells can help speed up healing for bone fractures (CIRM is funding work on that) and now researchers at Duke Health believe they have figured out how that works.
The research, published in the journal Nature Communications, identifies what the Duke team call the “youth factor” inside bone marrow stem cells. It’s a type of white blood cell called a macrophage. They say the proteins these macrophages produce help stimulate bone repair.
“While macrophages are known to play a role in repair and regeneration, prior studies do not identify secreted factors responsible for the effect. Here we show that young macrophage cells play a role in the rejuvenation process, and injection of one of the factors produced by the young cells into a fracture in old mice rejuvenates the pace of repair. This suggests a new therapeutic approach to fracture rejuvenation.”
Next step, testing this in people.
A new way to track stem cells in the body
It’s one thing to transplant stem cells into a person’s body. It’s another to know that they are going to go where you want them to and do what you want them to. University of Washington researchers have invented a device that doesn’t just track where the cells end up, but also what happens to them along the way.
The device is called “CellTagging”, and in an article in Health Medicine Network, Samantha Morris, one of the lead researchers says this could help in better understanding how to use stem cells to grow replacement tissues and organs.
“There is a lot of interest in the potential of regenerative medicine — growing tissues and organs in labs — to test new drugs, for example, or for transplants one day. But we need to understand how the reprogramming process works. We want to know if the process for converting skin cells to heart cells is the same as for liver cells or brain cells. What are the special conditions necessary to turn one cell type into any other cell type? We designed this tool to help answer these questions.”
In the study, published in the journal Nature, the researchers explain how they use a virus to insert tiny DNA “barcodes” into cells and that as the cells travel through the body they are able to track them.
Morris says this could help scientists better understand the conditions needed to more effectively program cells to do what we want them to.
“Right now, cell reprogramming is really inefficient. When you take one cell population, such as skin cells, and turn it into a different cell population — say intestinal cells — only about 1 percent of cells successfully reprogram. And because it’s such a rare event, scientists have thought it is likely to be a random process — there is some correct set of steps that a few cells randomly hit upon. We found the exact opposite. Our technology lets us see that if a cell starts down the right path to reprogramming very early in the process, all of its related sibling cells and their descendants are on the same page, doing the same thing.”
One of the biggest obstacles to transplanting organs from one person to another is that the immune system of the person getting the new life-saving organ often tries to reject it. The immune cells see the new material as “foreign” and attacks it, sometimes destroying it.
Right now, the only way to prevent that is by using powerful immunosuppressive drugs to keep the patient’s immune system at bay and protect the new organ. It’s effective, but it also comes with some long-term health consequences.
But now researchers at Tel Aviv University in Israel say they may have found a way around that, using the patient’s own stem cells.
The team says it was able to take fatty tissue from patients and, using the iPSC procedure, turn them into other kinds of cells to help repair different kinds of tissue.
In a story in the “Times of Israel”, Prof Tal Dvir, the lead researcher, said this new approach could theoretically be used to engineer any tissue type in the body.
“We were able to create a personalized hydrogel from the materials of the biopsy, to differentiate fatty tissue cells into different cell types and to engineer cardiac, spinal cord, cortical and other tissue implants to treat different diseases. Since both the cells and the material used derive from the patient, the implant does not provoke an immune response, ensuring proper regeneration of the defected organ.”
Dvir says the research, published in the journal Advanced Materials, has only been tested in animals so far but has shown great promise, helping regenerate damaged tissues in mice and rats. Their next goal is to see if they can replicate this in people.
“Theoretically we can work in every disease or disorder that cells are involved in, where tissue is dying. We can create the tissue to fix that injury by a simple injection of materials and cells at the injury site,”
While this has long been a goal of many stem cell researchers around the world, problems translating what looks good in animals into what works in people has invariably slowed down the progress of even the most promising approach. At least so far.
In 2017 Texas passed a sweeping new law, HB 810, which allowed medical clinics to provide “investigational stem cell treatments to patients with certain severe chronic diseases or terminal illnesses.” Those in favor of the law argued that patients battling life-threatening or life-changing diseases should have the right to try stem cell therapies that were involved in a clinical trial.
Now a new study, published in the journal Stem Cells and Development, looks at the impact of the law. The report says that despite some recent amendments t there are still some concerns about the law including:
It allows treatment only if the patient has a “severe, chronic” illness but doesn’t define what that means
It doesn’t have clearly defined procedures on tracking and reporting procedures so it’s hard to know how many patients might be treated and what the outcomes are
There is no Food and Drug Administration (FDA) oversight of the patients being treated
Because the treatments are unproven there are fears this will “open up the state to unsavory and predatory practices by individuals preying on vulnerable patients”
The researchers conclude:
“While HB 810 opens up access to patients, it also increases significant risks for their safety and financial cost for something that might have no positive impact on their disease. Truly understanding the impact of stem cell based interventions (SCBI) requires scientific rigor, and accurate outcome data reporting must be pursued to ensure the safety and efficacy behind such procedures. This information must be readily available so that patients can make informed decisions before electing to pursue such treatments. The creation of the SCBI registry could allow for some level of scientific rigor, provide a centralized data source, and offer the potential for better informed patient choices, and might be the best option for the state to help protect patients.”
Another CIRM-funded company gets RMAT designation
When Congress approved the 21st Century Cures Act a few years ago one of the new programs it created was the Regenerative Medicine Advanced Therapy (RMAT) designation. This was given to therapies that are designed to treat a serious or life-threatening condition, where early clinical stage trials show the approach is safe and appears to be effective.
Getting an RMAT designation is a big deal. It means the company or researchers are able to apply for an expedited review by the FDA and could get approval for wider use.
This week Poseida Therapeutics was granted RMAT designation by the Food and drug Administration (FDA) for P-BCMA-101, its CAR-T therapy for relapsed/refractory multiple myeloma. This is currently in a Phase 1 clinical trial that CIRM is funding
In this trial Poseida’s technology takes an immunotherapy approach that uses the patient’s own engineered immune system T cells to seek and destroy cancerous myeloma cells.
In a news release Eric Ostertag, Poseida’s CEO, welcomed the news:
“Initial Phase 1 data presented at the CAR-TCR Summit earlier this year included encouraging response rates and safety data, including meaningful responses in a heavily pretreated population. We expect to have an additional data update by the end of the year and look forward to working closely with the FDA to expedite development of P-BCMA-101.”
This means that five CIRM-funded companies have now been granted RMAT designations:
From time to time we invite patients or patient advocates to post a guest blog on the Stem Cellar. Today we are featuring Brigitta Burguess, a mother and writer from Michigan, who focuses on pregnancy, parenting, and children with disabilities. Brigitta writes for the HIE Help Center, a website that offers information and supportive resources for families of children with disabilities.
Because stem cells are the building blocks of the immune system, they possess the ability to develop into other types of cells. You can use stem cells to help repair tissues, organs, and blood vessels, and even treat a host of different diseases. This is done through stem cell harvesting and stem cell therapy. In stem cell therapy, stem cells are injected into injured tissues in the hopes of replacing damaged tissue and preserving existing tissues.
Every part of the human body contains stem cells. However, many areas of the body do not contain enough stem cells to make harvesting them worthwhile. Cord blood, the leftover blood collected from a baby’s umbilical cord or a mother’s placenta after birth, is especially beneficial because:
It provides a rich source of stem cells that can be changed into other types of cells and help to maintain and repair tissues
Its stem cells are immature and have not developed the ability to attack foreign cells, which makes them perfect for transplant
Its stem cells differ from embryonic stem cells in that they are considered adult stem cells and do not require the destruction of an embryo to harvest
It can be used to treat blood disorders, immune deficiencies, and certain cancers
Storing cord blood can help family and community members receive gene therapy treatment for the aforementioned conditions and diseases
The Applications of Stem Cell Therapy for Kids
Today, over 2,000 total cord blood stem cell transplants are performed annually, with the total number of cord blood banks worldwide reaching over 150. The innovations in stem cell therapy have made waves over the past four decades. Today, more than 80 difference diseases are being treated with cord blood stem cells.
In 2012, many clinical trials revealed that cord blood transplants were an effective treatment for cerebral palsy. Researchers also believe that cord blood stem cells have great potential in treating the neonatal brain injuries such as hypoxic-ischemic encephalopathy (HIE). As of right now, there is no indication that stem cell therapy can cure these conditions, but there is some evidence that it can lessen the severity of symptoms.
It is important to note that there is thus far no cure for hypoxic-ischemic encephalopathy (HIE) and resulting motor, cognitive, and/or intellectual disorders. Stem cell therapy seeks to limit the damage caused by HIE and reduce the severity of disabilities caused by HIE, but it is not a cure.
Because stem cell therapy is still in clinical trials, parents should think twice before going down this untested path, as no formal guidelines about administration protocol, dosages, safety, or treatment timeline have yet been established. Clinical trials are important for ensuring that treatments are safe and effective – unregulated treatments bear significant risk.