On December 12th we hosted our latest ‘Facebook Live: Ask the Stem Cell Team’ event. 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?

Dr. Kelly Shepard: Scientists have shown that manipulating cells through reprogramming, partial reprogramming, de‑differentiation, or trans‑differentiation can change cell properties.

In some cases, these changes make cells appear more youthful, with features like longer telomeres or improved ability to divide. But these same rejuvenating traits can be dangerous if they occur in the wrong context. A cell that starts growing or dividing at the wrong time or place could act like a cancer cell.

The biggest barriers to advancing this field are our limited understanding of partially reprogrammed cells and our inability to control their fate inside a living organism. Still, I expect step‑by‑step progress, beginning with specific tissues. For example, CIRM recently funded a project that uses reprogramming to create rejuvenated T cells to fight lung cancer. Researchers are also exploring ways to restore the repair capacity of aged muscle. Successes in these focused areas may eventually support broader applications.

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? 

Dr. Lila Collins: Hi Elvis, this story is still unfolding. I believe you’re referring to SanBio’s phase 1/2a stroke trial, which included Stanford as a site. The trialHere’s a streamlined, active‑voice version of your text:

Hi Elvis, this story is still developing. I believe you’re referring to SanBio’s phase 1/2a stroke trial, which included Stanford as a site. The trial tested the safety and feasibility of SanBio’s allogeneic stem cell product in chronic stroke patients who continued to have motor deficits even after completing physical therapy. As you noted, some participants showed encouraging motor improvements.

SanBio has since completed a larger, randomized phase 2b stroke trial and has shared high‑level results in a press release. SanBio ran a similar randomized trial in patients with chronic traumatic brain injury (TBI). In that study, the therapy produced positive motor recovery results. The product is now moving toward conditional approval in Japan and has received RMAT status in the U.S. for TBI, which could speed availability if future results hold. SanBio also plans further studies in stroke, so updates are likely.

Since you mentioned Stanford, it’s worth noting that Dr Gary Steinberg, a clinical investigator in the earlier SanBio trial, will soon launch a trial using a different product—neural progenitor cells—for chronic stroke. The therapy has shown promise in preclinical studies, and we’re hopeful it will perform well in patients.

I am a stroke survivor will stem cell treatment able to restore my motor skills?

Dr. Lila Collins: Hi Ruperto. Restoring motor function after stroke is a very active area of research. I’ll highlight a few ongoing stem cell trials. Please also review my colleague’s comments at the end of the blog about stem cell clinics to ensure any research you join is FDA‑regulated and as safe as possible.

Regarding stroke, I mentioned SanBio’s work on chronic motor loss earlier. Reneuron, based in the UK, is running a phase 2 trial using a neural progenitor cell therapy to treat persistent motor disability after chronic stroke. At Stanford, Dr. Gary Steinberg is preparing a clinical trial that will test a human embryonic stem cell‑derived neuronal progenitor cell in stroke.

Athersys is also advancing promising work in acute stroke. The company reported results from a randomized, double‑blind, placebo‑controlled phase 2 trial. After intravenous delivery, the cells improved a composite measure of recovery, including motor function. Rather than acting directly on the brain, Multistem appears to target the spleen and reduce the inflammatory response that worsens stroke injury.

Athersys is now recruiting for a phase 3 trial of Multistem in acute stroke, treating patients within 1.5 days. The trial has RMAT status and a special protocol assessment from the FDA. If the study meets its agreed‑upon goals, the therapy could move to market. Results are expected 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: You’re right that most cell therapies for stroke focus on ischemic stroke. Ischemic strokes make up about 85 percent of all cases. Hemorrhagic strokes are less common but more deadly. Bleeding in or around the brain damages neurons and can raise pressure in the skull, causing further injury. Early treatment focuses on stopping the bleeding and removing blood from the brain.

Most therapies in development target ischemic stroke, but treatments that repair neuronal damage or eventually replace lost neurons could also help patients after hemorrhagic stroke.

We are aware of an acute hemorrhagic stroke clinical trial underway at the Mayo Clinic in Jacksonville, Florida.

I had an Ischemic stroke in 2014, and my vision was also affected. Can stem cells possibly help with my vision issues.

Dr. Lila Collins: Hi James. Vision loss from stroke is complex, and the type of loss depends on where the stroke occurred — in the eye, the optic nerve, or the parts of the brain that control eye movement or interpret vision. The effects can include:

• Vision loss from retinal damage
• Normal eye function but damage to the brain regions that control eye movement
• Damage to the brain areas that process visual information

Each problem requires a different cell‑replacement approach to repair the retina or the affected parts of the brain.

Researchers are actively exploring ways to replace lost neurons, but this work is still in early research stages. It’s challenging because new neurons must form precise connections to restore function.

Is there any stem cell therapy for optical nerve damage?

Dr. Ingrid Caras: There’s currently no proven stem cell therapy for optic nerve damage, despite claims from some unregulated clinics. Early gene therapy studies in mice are more promising.

Researchers used an AAV virus to deliver growth factors that stimulated damaged nerves to regrow. These findings suggest it may be possible to restore some vision in people who lose sight from optic nerve damage caused by glaucoma.

****************************

My question is: If they can inject human retinal progenitor, why not fully developed photoreceptors?

Dr. Kelly Shepard: Studies in several tissues — including blood, pancreas, heart, and liver — show that fully mature cells rarely engraft well after transplantation. They often fail to take hold or survive long term in a new environment. In contrast, less‑mature progenitor cells engraft more effectively. They establish themselves in the tissue and then mature over time.

This issue highlights a key challenge for new therapies: identifying the best cell type to use and the best time to deliver it.

When will jCyte publish their Phase IIb clinical trial results.

Dr. Ingrid Caras: The results will be available sometime in 2020.

What percentage of the injected hRPC are currently surviving?

Dr. Kelly Shepard: We can study these questions in the lab and in animal models, but only a clinical trial can recreate the real conditions and stresses cells face after transplantation into a human. We may not know the full answer until clinical trials are completed and we can evaluate the results. Even then, tracking the cells can be difficult because we can’t always remove tissue for analysis or use labeled cells that are easy to trace.

Dr. Ingrid Caras: Although these cells can develop into photoreceptors, we don’t yet know if they do so after being injected into a patient’s eye. Current data suggest the cells mainly act by releasing growth factors that rescue or repair damaged retinal cells. They may slow or prevent further vision loss. They may also help damaged but still‑living retinal cells recover function, which could improve vision.

**********************************

What advances have been made using stem cells for the treatment of Type 2 Diabetes?

Dr. Ross Okamura: Type 2 diabetes (T2D) develops when the body can’t maintain normal glucose levels because it resists insulin’s effects or doesn’t produce enough insulin from pancreatic beta cells.

Type 1 diabetes (T1D) differs because the immune system destroys the pancreatic beta cells. Patients need insulin immediately, unlike many T2D cases where insulin needs increase over time. The only curative option has been donor pancreas or islet transplantation, but donor tissue is scarce. These transplants also require immune‑suppressive drugs, which carry risks, though for some patients—especially those with life‑threatening hypoglycemia—the benefits outweigh the concerns.

To address the limited supply of donor tissue, researchers are working to generate insulin‑secreting beta cells from pluripotent stem cells. Early clinical data from ViaCyte’s CIRM‑funded trial show that implanted allogeneic stem‑cell‑derived cells can produce circulating c‑peptide, a marker of insulin production, in T1D patients. While this trial does not target insulin‑dependent T2D directly, successful engraftment of stem‑cell‑derived beta cells could help all insulin‑dependent patients.

There is also a strong scientific rationale for testing patient‑derived pluripotent stem‑cell‑based insulin‑producing cells in insulin‑dependent T2D.

Is there any news on clinical trials for spinal cord injury?

Kevin McCormack: The clinical trial that CIRM funded with Asterias—now part of Lineage Cell Therapeutics—is complete, and the results were encouraging. In a November 2019 news release, Brian Culley, CEO of Lineage, described the findings:

“We remain extremely excited about OPC1’s potential to improve motor recovery in spinal cord injury patients. We haven’t seen any other investigational SCI therapy report outcomes as strong as OPC1, especially with continued gains beyond one year. Most patients continued to improve in Year 2, with motor‑level gains matching or exceeding their Year 1 results. For example, five of six Cohort 2 patients regained two or more motor levels on at least one side at Year 2, compared with four of six at Year 1. A single motor‑level gain enables arm movement, which affects basic tasks like feeding, dressing, and transferring from a wheelchair—meaningful improvements in independence and quality of life. Just as important, OPC1’s safety profile remains excellent two years after treatment, based on MRIs from Year 2 follow‑up visits. We look forward to sharing more SCiStar data as patients return for scheduled assessments.”

Lineage Cell Therapeutics planned to meet with the FDA in 2020 to discuss the next steps for this therapy.

The only other active recruiting trial I’m aware of is run by Neuralstem. You can find details about that study on the 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?

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?

Dr. Kelly Shepard: Autism and related spectrum disorders include many conditions that share some features but arise from different causes. We still don’t fully understand these origins. Identifying how a disorder begins and how it affects cells and systems is the first step toward new therapies. In 2009, CIRM held a workshop to explore how stem cell research could help. One major recommendation was to use stem cells and new technologies to create neurons and other tissues in the lab from individuals with autism, allowing detailed study. CIRM acted on this and funded early‑stage projects on Rett syndrome, Fragile X, Timothy syndrome, and other spectrum disorders. These studies have not yet produced therapies ready for human testing, but the field remains active.

Outside CIRM funding, more advanced studies are testing whether umbilical cord blood or other stem cell types can help treat autism. One example is an ongoing clinical trial at Duke University.

**********************************

PARKINSON’S DISEASE

What is happening with Parkinson’s research?

Dr. Kent Fitzgerald: Parkinson’s disease has a strong focus in regenerative medicine and stem cell research. The loss of dopamine‑producing neurons in the brain makes the disease a natural target for cell‑replacement therapies. Restoring these cells could ease symptoms, much like how L‑dopa temporarily replaces dopamine. But L‑dopa loses effectiveness over time, while repairing or replacing the damaged cells could offer a longer‑lasting solution.

Because a specific group of cells in one brain region dies in Parkinson’s, many labs and clinicians have tried to restore function by transplanting new dopamine‑producing cells. Early studies using fetal tissue showed some promise but produced mixed results. Researchers learned that they must transplant the correct subtype of cells to avoid side effects. The field has since moved away from fetal tissue and now focuses on stem‑cell‑derived dopamine neurons.

One CIRM‑funded project led by Jeanne Loring is developing a therapy using a patient’s own reprogrammed stem cells, which may reduce the risk of immune rejection. Other teams are pursuing gene‑therapy approaches. For example, a CIRM‑supported clinical trial led by Krystof Bankiewicz is testing the delivery of the GDNF gene to boost the activity of struggling neurons in the Parkinson’s brain.

Most current work still centers on replacing or restoring the dopamine‑producing neurons lost in the disease.  

Any plans for Huntington’s?

Dr. Lisa Kadyk: Several new therapies for Huntington’s disease are moving through preclinical and clinical development, including CIRM‑funded programs. One project led by Dr. Leslie Thompson at UC Irvine is developing a cell therapy made from neural stem cells derived from embryonic stem cells. When researchers inject these cells into the brains of mice with the Huntington’s mutation, the cells engraft and begin forming new neurons. The treated mice show behavioral and electrophysiological improvements, suggesting the approach could help people with the disease.

CIRM is currently funding Dr. Thompson’s team to run rigorous safety studies in animals. These studies will support a future FDA application to begin a clinical trial in humans.

Other therapies that don’t involve cells are also in clinical testing. Ionis and Takeda are using antisense oligonucleotides to lower production of the Huntington protein. UniQure and Voyager are testing a similar HTT‑lowering strategy that uses miRNAs.

Will clinical trials underway for TBI in adults but will they be scalable to pediatric use and s there a time window period in which stem cells should be administered after an injury?

Dr. Kelly Shepard:  TBI and other nervous system injuries trigger intense inflammation, which can interfere with healing. Some therapies work best after this inflammation subsides. Other approaches aim to treat chronic injuries that occurred long before treatment. The right timing depends on how the therapy works. For example, is the goal to grow new neurons, protect surviving cells, reduce seizures, or fill a structural gap left after inflammation? Each goal may require a different treatment window.

We still have much to learn about the brain and its complex networks. No single strategy—whether replacing neurons or reducing inflammation—can solve every problem. But well‑designed trials can still provide valuable insights, even if a therapy falls short. That knowledge will guide future approaches as our tools and understanding improve.

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 shown that nutrient media from MSC cultures can have therapeutic effects in animal models. Scientists can isolate these factors, but no one has yet identified a specific molecule or combination that replicates the benefits of the full, undefined mixtures found in media or exosomes. No regulatory agency has approved a clinical therapy using this approach.

What practical measures are being taken to address unethical practitioners giving stem cell advances a bad reputation?

Dr. Geoff Lomax: When I researched the history of unethical medical practitioners, I even found an 1842 reference to “quack medicines,” so the problem is hardly new. Even then, the author urged society to “become acquainted with the facts.”

In California, we’re taking steps to help patients understand the facts about stem cell treatments and to support FDA‑authorized therapies for unmet medical needs.

First, CIRM worked with Senator Hernandez in 2017 to create a law that requires providers to tell patients when a stem cell therapy has not been approved by the FDA. We continue to work with the State Legislature and the Medical Board of California to strengthen policies that ensure patients receive accurate information.

Second, our Alpha Stem Cell Clinics network has supported more than 100 FDA‑authorized clinical trials, helping advance responsible research for patients who need new treatment options.

Do stem cells have benefits for patients going through chemotherapy and radiation therapy?

Dr. Kelly Shepard: Several groups, including some funded by CIRM, are exploring stem cell therapies to counter the effects of chemotherapy or radiation. Early‑stage work focuses on using stem‑cell‑derived neural cells to replace or restore brain cells damaged by treatment. A different approach at City of Hope is testing whether a bone marrow transplant using specially modified stem cells can protect patients from the chemotherapy used to treat glioblastoma. This program is nearing completion of its final preclinical work and will apply to the FDA to begin human trials if the data look good.

Dr. Ingrid Caras: That’s an important and timely question. A Phase 1 trial is now testing a novel stem/progenitor cell taken from healthy umbilical cord tissue. In animal studies, these cells reduced the toxic effects of chemotherapy and radiation and sped recovery. Researchers are now evaluating them in patients receiving high‑dose chemotherapy.

At Stanford, Dr. Michelle Monje is studying how damage to brain stem cells contributes to “chemobrain.” Her work shows that harm to stem cells that produce oligodendrocytes plays a major role. With CIRM support, she has identified small molecules that may help prevent or reduce these cognitive symptoms.

Is it possible to use a technique developed to fight one disease to also fight another?

Dr. Lisa Kadyk: Yes, the same general technique can often treat more than one disease, though each application needs customization. The approach you mentioned is an autologous gene‑modified bone marrow transplant, meaning the patient’s own cells are used. This method works for single‑gene mutations that affect the blood and immune system.

For example, in “bubble baby” diseases, one mutation blocks immune‑cell development, leaving children unable to fight infections. To treat this, doctors collect the child’s blood stem cells from the bone marrow, add a normal copy of the faulty gene, and then return the corrected cells to the patient. These cells repopulate the blood system with healthy immune cells and can cure the disease.

A similar strategy can treat sickle cell disease, which is also caused by a single mutation in a blood‑cell gene (beta‑hemoglobin). The steps are the same, but the therapeutic gene introduced into the patient’s stem cells is different.

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?

Dr. Kelly Shepard: CIRM has always believed that basic research is essential to regenerative medicine. Over the past decade, CIRM invested $904 million in discovery‑stage research and another $215 million in training grants that supported graduate students, postdocs, clinical fellows, undergraduates, master’s students, and even high school students doing basic stem cell research. In recent years, with limited funds left, CIRM chose to direct most remaining resources toward later‑stage projects to help them move from the lab to the clinic.

Even so, CIRM still supports basic research through its Bridges and SPARK training programs, where students at multiple levels work in world‑class stem cell labs — many of the same labs previously funded by CIRM’s basic research grants. While NIH and other funders continue to invest heavily in stem cell research ($1.8 billion from NIH in 2018 alone), CIRM believes that sustained support for basic science, especially in key areas and emerging opportunities, remains critical for discovering and developing new treatments.

Explain the differences between gene therapy and stem cell therapy?

Dr. Stephen Lin:  Gene therapy directly modifies a patient’s cells to treat disease. Most approaches use harmless, engineered viruses to deliver a gene into the cells. The field has seen major clinical successes, including the first FDA‑approved gene therapy for a genetic form of blindness in 2017 and additional approvals for genetic forms of spinal muscular atrophy and amyloidosis.

Stem cell therapy introduces stem cells into a patient to replace damaged or defective cells. These therapies can use pluripotent stem cells, which can become any cell type, or progenitor cells, which can develop into a limited set of cells. For example, hematopoietic stem cells from bone marrow can generate all blood and immune cell types, while mesenchymal stem cells from fat can form bone, cartilage, and fat. These cells may come from the patient (autologous) or a donor (allogeneic).

Gene therapy often pairs with cell therapy. Clinicians collect a patient’s cells, modify them in the lab to correct a mutation or insert a healthy gene, and then return them to the patient. This “ex vivo gene therapy” includes CAR‑T cells for cancer and gene‑modified blood stem cells for disorders like severe combined immunodeficiency and sickle cell disease. Many patients have already seen significant improvement or even cures from these approaches.

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?

Dr. Stephen Lin:  Stem cell therapies must submit extensive data to the FDA before starting clinical trials. This includes animal studies showing the therapy works and identifying effective dose levels. Researchers use these data to estimate safe and potentially therapeutic doses for human trials. CIRM funds early‑stage studies to generate this information and prepare therapies for clinical testing.

Clinical trials often test multiple doses to find the one that works best. Dosing cell therapies is challenging because survival, engraftment, and immune rejection can affect how many cells ultimately take hold. CIRM supports studies designed to address these issues and provide the best possible dose estimates.

Is there any research on using stem cells to increase the length of long bones in people?

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.