Stem cell stories that caught our eye: Immune therapy for HIV, nerves grown on diamonds and how stem cells talk

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Trendy CAR T therapy tried on HIV.  The hottest trend in cancer therapy today is using CAR-T cells to attack and rid the body of cancer. Technically called chimeric antigen receptors the technology basically provides our own immune system with directions to cancer cells and keys to get inside them and destroy them. A CIRM-funded team at the University of California, Los Angeles, has now tried that same scheme with HIV.

Jerome Zack (left) and Scott Kitchen, found that the technique decreased HIV levels in mice by 80 to 95 percent.

Jerome Zack (left) and Scott Kitchen, found that the technique decreased HIV levels in mice by 80 to 95 percent.

The researchers worked with mice bred to have a human immune system so that HIV affects them similarly to humans. They harvested their blood-forming stem cells and inserted a CAR that recognized HIV. After giving the stem cells back to the mice they produced T cells capable of seeking out and destroying about 90 percent of the virus. The technique has a ways to go, but the study’s lead author noted their ultimate goal in a University press release picked up by HealthCanal:

“We hope this approach could one day allow HIV-positive individuals to reduce or even stop their current HIV drug regimen and clear the virus from the body altogether,” said Scott Kitchen. “We also think this approach could possibly be extended to other diseases.”

Nerves grown on diamonds. Diamonds are so chemically non-reactive our bodies would not recognize them as foreign. But they can also be made to conduct electricity, which could make nerves grown on their surface able to be turned on and off with electrical impulses. When developing cell therapy for several neurologic diseases the ability to control the activity of replacement cells could be critical to success—making new research by a team in Britain and Ireland intriguing, if very preliminary.

They doped diamonds with boron to make them able to conduct electricity and then used them as a surface for growing nerve stem cells that could later be turned into nerves. They then succeeded in growing nerves long term on the diamonds.

“We still have a lot more fundamental studies of the neuron/diamond interface to perform,” said Paul May of the University of Bristol. “[But] the long term possibilities for this work are exciting.  Long-lifetime diamond bio-implants may offer treatments for Parkinson’s, Alzheimer’s, stroke or even epilepsy.”

Materials Today wrote a piece explaining the work.

Some stem cells talk over “land lines.” Most cellular communication works through chemical signals that get dispatched by one cell and received by others. It turns out that some types of stem cells communicate by sending out tiny nanotubes, sort of a cellular land line.

A team at the University of Michigan and the University of Texas Southwestern Medical Center found the new form of communication working with fruit flies. Yukiko Yamashita, a senior author of the paper from Michigan explained why it is so important to get a better understanding of cell-to-cell communication in a university press release picked up by ScienceNewsline:

“There are trillions of cells in the human body, but nowhere near that number of signaling pathways. There’s a lot we don’t know about how the right cells get just the right messages to the right recipients at the right time.”

In a classic example of the beauty of young minds in science, prior images of these stem cells had shown the nanotubes, but they had been overlooked until a graduate student asked what they were.

Phase 3 melanoma trial explained. When a new therapy gets into its third and final phase of testing it is make or break for the company developing the therapy and for patients who hope it will become broadly available. CIRM recently provided funding to our first phase three clinical trial, one aimed at metastatic melanoma being conducted by Caladrius Biosciences.

The CEO of the company, David Mazzo, gave an interview with The New Economy this week that does a nice job of explaining the goal of the therapy and how it is different from other therapies currently used or being developed. The therapy’s main difference is its ability to target the cancer-inducing cells thought to responsible for the spread of the disease.

High school and middle school teachers use summer to develop stem cell lesson plans.

At CIRM, we have developed programs that try to capture and train budding young scientific minds starting in the upper reaches of k-12 schools, through undergrad college, graduate work and post doctoral training. So, we are thrilled when one of our partner institutions takes on that challenge with a new robust effort.

Piner High teacher Heather Benson practices micropipetting.

Piner High teacher Heather Benson practices micropipetting.

The Buck Institute for Research on Aging in Marin County conducted two programs this month to empower local school teachers to build stem cell science into their lesson plans for the coming year. Both initiatives asked the teachers to give up three days of their summer vacation. The Buck’s Julie Mangada spearheaded the initiative.

Twelve middle school teachers from Marin participated in “STEAM Engine 2015,” in which they created an outline for a curriculum unit on how cells work together and process sensory information. If they teach that outline this fall for a two-four-week period they will get $200 per class for supplies and a bonus $700 stipend in the program partnered with the Marin County Office of Education.

In addition, three high school teachers from neighboring Sonoma County attended a three-day externship to develop integrated lesson plans on the theme: “How have past discoveries built the foundation for stem cell research to cure disorders in the present.” All three teach at Piner High. One, Judy Barcelon, described what she took away from the three days:

“I became inspired to challenge my students with higher level science concepts so they can understand how aging and disease happened on a cellular level.”

The three teachers and their students will work together this fall as a team to create a timeline of technical advances while learning the function of those techniques. They will then create research proposals to foster understanding of one specific disease. The activities will culminate on the CIRM-organized international Stem Cell Awareness Day October 14 with a presentation by Buck’s Mangada as well as someone from CIRM.

The local Press Democrat ran an article about the program last week.

Stem cell stories that caught our eye: Parkinson’s in a dish, synthetic blood, tracking Huntington’s and cloning

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

3D nerve model for Parkinson’s. The wave of successes in making more complex tissues in three dimensional lab cultures continues this week with a team in Luxembourg creating nerves from stem cells derived from Parkinson’s patients that assembled into complex connections in the lab.

Nerve cells made from skin cells. Credit: Luxembourg Centre for Systems Biomedicine (LCSB), 2015

Nerve cells made from skin cells. Credit: Luxembourg Centre for Systems Biomedicine (LCSB), 2015

The name of the journal where the group published their results, Lab on a Chip, says a lot about where the field is going. While many have grown the dopamine-producing nerves lost in Parkinson’s disease in two dimensional cultures, the new technique better replicates the disease state and does it about 10-fold cheaper because the 3D bioreactors used can be automated and use less of the reagents needed to grow the cells and to tell them to become the right nerves.

They started with skin samples from patients and reprogrammed them into iPS-type stem cells. After those cells are placed in the vessel, they are matured into 90 percent pure dopamine-nerves. At that point they are ideal for testing potential drugs for any impact on the disease. The senior researcher, Ronan Fleming, explained the benefit in a press release from the University of Luxembourg, picked up by ScienceDaily:

“In drug development, dozens of chemical substances can therefore be tested for possible therapeutic effects in a single step. Because we use far smaller amounts of substances than in conventional cell culture systems, the costs drop to about one tenth the usual.”

Synthetic blood from stem cells. Making synthetic blood, particularly for people with rare blood types for which there are few donors, has long been a goal of science. Now, the British National Health Service (NHS) says it expects to begin giving patients at least one component of lab-made blood—red cells—by 2017.

Starting with adult stem cells grown in just the right solution they hope to produce large quantities of red blood cells. Initially they plan to give only small quantities to healthy individuals with rare blood types to compare them to donor blood.

“These trials will compare manufactured cells with donated blood,” said Nick Warkins of the NHS. “The intention is not to replace blood donation but provide specialist treatment for specific patient groups.”

The story got wide pick up in the British press including in the Daily Mail and in several web portals including Rocket News.

Tracking Huntington’s spread in the brain. A CIRM-funded team at the University of California, Irvine, has developed a way to track the spread of the mutant protein responsible for progression of Huntington’s disease. They were able to accurately detect the mutant protein in cerebrospinal fluid and distinguish between people who carried the mutation but were pre-symptomatic from those that had advanced disease.

The protein appears to be released by diseased cells and migrates to other cells, seeding additional damage there. Measuring levels of the protein should allow physicians to monitor progression of the disease ahead of symptoms.

“Determining if a treatment modifies the course of a neurodegenerative disease like Huntington’s or Alzheimer’s may take years of clinical observation,” said study leader Dr. Steven Potkin. “This assay that reflects a pathological process can play a key role in more rapidly developing an effective treatment. Blocking the cell-to-cell seeding process itself may turn out to be an effective treatment strategy.”

Medical News Today wrote up the research that the team published in the journal Molecular Psychiatry.

Good overview of cloning. Writing for Medical Daily, Dana Dovey has produced a good overview of the history of cloning, and more important, the reasons why reproductive cloning of human is not likely to happen any time soon.

She describes the important role a number of variations on cloning play in scientific research, and the potential to create personalized cells for patients through a process known as therapeutic cloning. But she also describes the many problems with reproductive cloning as it is practiced in animals. It is very inefficient with dozens of eggs failing to mature and often results in animals that have flaws. She quotes Robert Lanza of Advanced Cell Technologies (now Ocata Therapeutics):

“It’s like sending your baby up in a rocket knowing there’s a 50-50 chance it’s going to blow up. It’s grossly unethical.”


Fate of our nerve stem cells determined early in embryo so the few we have as adults have very specific roles

Adult nerve stem cells fall in the category of allusive creatures. A few scientists still question their existence and most suggest they exist in small numbers only in one or two locations in the adult brain. In any case, all agree they are not particularly good at the normal function of stem cells—making repairs to their surrounding tissue.

A research team at the University of California, San Francisco, recently published results providing two reasons why adult nerve stem cells are not very robust. First they don’t self-renew—make more copies of themselves—on a regular basis.

While we have many types of nerves in our brains, our adult stem cells seem preprogrammed to form certain ones.

While we have many types of nerves in our brains, our adult stem cells seem preprogrammed to form certain ones.

Second, the ones you were born with were preprogrammed before birth to become only a narrow subset of the many nerves we need for a fully functioning brain.

Working in mice, the team led by Arturo Alvarez-Buylla found several types of stem cells on the walls of cavities in the brain and each was pre-programmed to be “progenitors” for a specific subset of nerves. Like progenitors appeared to be lumped together by location and the team also tracked the time during embryo development when these destiny designations are made.

These results could make folks reconsider how they might use adult nerve stem cells for therapy. Alvarez-Buylla explained in a UCSF press release picked up by ScienceNewsline:

“It may be unwelcome news for those who thought of adult neural stem cells as having a wide potential for neural repair. Instead, it looks as if that potential is narrowed down very early during embryonic development. It’s almost as if the embryo is planning for the future.”

He went on to argue that the study points out the critical importance of understanding how stem cells develop and change in the embryo because that knowledge will guide how we use the various stem cells in therapy.

CIRM did not fund this study, but we do fund work in the Alvarez-Buylla lab that seeks to create nerve cells that can be implanted into people with diseases like epilepsy that result from an imbalance between different types of nerves.

Hed: Stem cell stories that caught our eye: the why’s of heart failure, harnessing stem cells’ repair kits and growing organs

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Stem cell model sheds light on heat failure. Pretty much everyone who has heart failure due to cardiomyopathy—where the heart muscle doesn’t work as effectively as it should—or has a condition that could lead there, is taking a beta blocker. The beta-andrenergic pathway, a key molecular pathway in the heart, dysfunctions in patients with cardiomyopathy and we have never known exactly why. We just know these drugs help.

Now, a team at Stanford led by Joseph Wu has used skin samples from patients and normal subjects to create reprogrammed iPS type stem cells, grown them into heart muscle, and compared them at a very fine-tuned molecular level.

Some patients have a mutation in a protein called TNNT2 in heart muscle fibers, which regulates muscle contraction. So, one thing they looked at was the impact of that mutation. Wu’s team followed the actions triggered by this mutation and found they lead to the beta-andrenergic pathway. Wu explained the value he sees in this fundamental understanding of the disease in a Stanford press release:

“As a cardiologist, I feel this basic research study is very clinically relevant. The beta-andrenergic pathway is a major pharmaceutical target for many cardiac conditions. This study confirms that iPS-cell-derived cardiomyocytes can help us understand biologically important pathways at a molecular level, which can aid in drug screening.”

CIRM did not fund this project but we do fund other projects in Wu’s lab including one to advance the use of iPS cells as models of heart disease, one using tissue engineering to repair damaged areas of the heart and one using embryonic stem cells to generate new heart muscle.

Harnessing stem cells’ repair kits. Stem cells repair tissue in multiple ways, but primarily by maturing into cells that replace damaged ones or by excreting various chemicals that give marching orders to neighboring cells to get busy and make the repairs. Those chemicals, collectively called paracrine factors, get excreted by the stem cells in vessels known as exosomes. So, a team at Temple University in Philadelphia decided to try injecting just the exosomes, rather than whole stem cells to repair heart damage. It seemed to work pretty well in mice.

Stem cells release exosomes, tiny vessels that act as repair kits.

Stem cells release exosomes, tiny vessels that act as repair kits.

After treatment with the exosomes, mice with induced heart attacks showed fewer heart cells dying, less scar tissue, more development of new blood vessels and a stronger heart function. The head of the Temple team, Raj Kishore, described the result in a university press release distributed by EuekaAlert:

“You can robustly increase the heart’s ability to repair itself without using the stem cells themselves. Our work shows a unique way to regenerate the heart using secreted vesicles from embryonic stem cells.”

The team went on to isolate a specific regulatory chemical that was among the most abundant in the exosomes. That compound, a type of RNA, produced much of the same results when administered by itself to the mice—intriguing results for further study.

Good primer on using stem cells to grow organs. The Wisconsin State Journal ran a nice primer in both video and prose about what would theoretically go into building a replacement organ from stem cells and some of the basic stem cell principals involved. The piece is part of a series the paper produces with the Morgridge Institute at the University of Wisconsin. This one features an interview with Michael Treiman of Epic Systems:

“The biggest challenge right now is that we can push a stem cell to be a particular type of cell, but in a tissue there’s multiple cells. And an organ like your heart or brain isn’t just made of one cell type; it’s made of many cell types working together.”

Neat trick grows two parts of the brain and gets them to communicate

Over the past year or so, teams around the world have reported using stem cells to make increasingly complex portions of the brain. Earlier this month we wrote about a team at Stanford who had grown “organoids” that simulated the brain’s cortex with both nerves and support cells that communicated back and forth with each other. Now, a team at the National Institutes of Health has created nerves from two distinct parts of the brain and got them to make connections for the cross-talk that makes our brains so wonderfully complex.

Cortex nerves (green) and mDA nerves (red) shown connecting with fine tendrils.

Cortex nerves (green) and mDA nerves (red) shown connecting with fine tendrils.

The researchers used reprogrammed iPS type stem cells made from skin samples to create two types of nerves in two separate chambers of a lab container. One, called mesencephalic dopaminergic (mDA) nerves, has been linked to disorders like drug abuse, schizophrenia and attention deficit-hyperactivity disorder. In the other chamber they grew nerves that became part of the brain’s cortex responsible for memory, attention and language.

After coaxing the stem cells to become the two distinct nerve types in their own chamber, the researchers removed a barrier between the chambers and observed the two cell types making the kind of connections needed for thought.

The lead researcher, Chun-Ting Lee described the value of this new system in understanding disease using human pluripotent stem cells (hPSCs), either iPS or embryonic:

“This method, therefore, has the potential to expand the potential of hPSC-derived neurons to allow for studies of human neural systems and interconnections that have previously not been possible to model in vitro.”

A press release from the journal Restorative Neurology and Neuroscience was picked up by ScienceNewsline.

Stem cell stories that caught our eye: regenerating limbs on scaffolds, self regeneration via a drug, mood stem cells, CRISPR

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Regenerating a limb, or at least part of it. Many teams have generated organs or parts of organs in animals by starting with a dead one. They literally wash away all the cells from the donor organ using a detergent so that they are left with a framework of the cells’ connective tissue. Then they seed that scaffold with stem cells or other cells to grow a new organ. A team at Massachusetts General Hospital has now used the same process to generate at least part of a rat limb.

The news cells growing on the donor limb scaffold in a bioreactor

The news cells growing on the donor limb scaffold in a bioreactor

It took a week to get the tiny little leg fully cleaned up and then another two weeks for the seeded cells to repopulate the scaffold left behind. That cellular matrix seems to send signals to the seeded cells on what type of tissue to become and how to arrange themselves. The team succeeded in creating an artificial limb with muscle cells aligned into appropriate fibers and blood vessels in the right places to keep them nourished. The researchers published their work in the journal Biomaterials and the website Next Big Future wrote up the procedure and provided some context on the limitations of current prosthetic limbs. The author also notes that the researchers have a lot more work to do, notably to prove they can get nerves to grow and connect at the point of transplantation to the “patient” animal. Discover also wrote a version of the story.

Getting the body to regenerate itself. A strain of mice discovered 20 years ago has led a multi-institution team to a possible way to get the body to regenerate damaged tissue, something the mouse discovered two decades ago can do and other mammals cannot. The researchers found that those mice have one chemical pathway, HIF-1a, that is active in the adult mice but is normally only active in the developing embryo. When they pushed that chemical path to work in normal mice those mice, too, gained the power to regenerate tissue. Ellen Heber-Katz from the Lankenau Institute for Medical Research outside of Philadelphia was quoted in the institute’s press release on Health Medicine Network.

“We discovered that the HIF-1a pathway–an oxygen regulatory pathway predominantly used early in evolution but still used during embryonic development–can act to trigger healthy regrowth of lost or damaged tissue in mice, opening up new possibilities for mammalian tissue regeneration.”

Heber-Katz led the team that included researchers from the company Allergan and the University of California, Berkeley. In order to activate the HIF-1a pathway they basically took the natural brakes off it. Another cellular chemical, PHD normally inhibits the action of HIF-1a in adults. The researcher turned the table on PHD and inhibited it instead. The result, after three injections of the PHD inhibitor over five days the mice who had a hole punched in their ear healed over the hole complete with cartilage and new hair.

Regulating memory and mood. It turns out your brain’s hippocampus, the section responsible for both memory and mood, has not one type of stem cell replenishing nerves, but two. And those two types of stem cells give rise to different types of nerves, which may account for the highly varied function of this part of the brain. Researchers at the University of Queensland in Australia isolated the two types of stem cells and then let them grow into nerves but the nerves from each expressed different genes, which means they have different functions. The lead researcher on the study, Dhanisha Jhaveri, discussed the findings in a press release picked up by Science Daily:

“The two cell groups are located in different regions of the hippocampus, which suggests that distinct areas within the hippocampus control spatial learning versus mood.”

The research provides fodder for future work looking into the treatment of learning and mood disorders. Review of the now celebrity tool, CRISPR. I don’t think I have ever seen so much ink and so many electrons spilled over a science tool as I have seen for CRISPR, particularly for one few scientists can tell you what the acronym stands for: Clustered Regularly Interspaced Short Palindromic Repeats. It is basically a fluke in the genes of several bacteria in which some of the base pairs that make up their DNA get repeated at regular intervals. Their configuration confers the ability for CRISPR segments to be used to disrupt or change specific genes in other organisms. Heidi Ledford writing for Nature in the journal’s news section provides a great wrap-up of what the technology is and what it can do, but also provides some caveats about its efficiency, accuracy, ethical concerns, and occasionally just not understanding how it works. The Nature team provides some valuable infographics showing the history of the science and on the rapid adoption of the technology as shown in publications, patents and funding. They also published an infographic on using CRISPR for “gene drive,” a way to push a modified trait through a population quickly, such as a mutation that could stop mosquitos from transmitting malaria. This potential drives much of the concern about misuse of the tool. But scientists quoted in the piece also provide more mundane reasons for moving slowly in thinking about using the therapy for patients. One of those is that it can sometime cause a high rate of “off-target” gene edits; simply put, cutting DNA in the wrong place. But as a research tool, there is no doubt it has revolutionized the field of gene modification. It is so much faster and so much cheaper than earlier gene editing tools; it is now possible for almost any lab to do this work. The piece starts out with an anecdote from CIRM-grantee Bruce Conklin of the Gladstone Institutes, talking about how it completely changed the way his lab works.

“It was a student’s entire thesis to change one gene,” Conklin said, adding “CRISPR is turning everything on its head.”

Genes+Cells: Stem cells deliver genes to make T cells resistant to HIV

This summer the first patients will be enrolled in a clinical trial using a form of genetic scissors to alter the DNA in their stem cells to give their immune systems a desired trait—resistance to HIV. The procedure will alter the patients’ blood-forming stem cells so that they can permanently make immune system T cells that HIV cannot infect. For the lead researcher on the team at City of Hope in Duarte, California, this trial caps some 25 years of effort to use genetic manipulation to halt the insidious virus.

That researcher, John Zaia, first began using gene therapy techniques to help patients resist the virus in the early 1990s, but the

John Zaia

John Zaia

first techniques were not very efficient in making the needed genetic alterations. Then the death of a test patient in a trial for another disease put the entire field on hold for many years. But the logic of making people genetically resistant to HIV was so compelling Zaia periodically tried new techniques and has reason to believe he is working with one now that can get the job done.

The molecular scissors, technically called zinc finger nucleases, can very precisely splice open a persons DNA and inactivate specific genes. For patients with HIV they target the gene for CCR5, which is a protein on the surface of T cells that HIV needs to use like a lock and key to get into the cells. If it cannot get in, it cannot infect. The scissor has been developed by a company in Richmond, California, Sangamo Biosciences, and researchers working with the company have already reported results showing the process works in adult T cells. Zaia’s team hopes to take those positive results to the next level by altering the blood-forming stem cells, which should be able to supply a much larger and permanent supply of HIV-resistant T cells.

With the great success of antiretroviral therapy, many question the need for intervention at this level. Not HIV advocate Mathew Sharp. Read about his journey with HIV and why he became a subject of that early zinc finger trial in adult T cells, saw improvement and holds out hope for even better therapies in the future.

Zaia’s trial is one of four CIRM-funded projects in or near clinical trials that seek to use genetic manipulation to give a person’s immune cells a desired trait. Two seek to confer resistance to HIV and two seek to make the cells better at fighting cancer.

The Clinical Trial

To be in the trial, patients must:
Have no detectable virus on viral therapy
Have CD4 cell counts between 200 and 500
Not positive for virus that does not require CCR5 for entry
Have no CCR5 mutations already in their cells

Enrollment centers
Two in Los Angeles, one in Connecticut, one in San Francisco

Treatment location
All patients will be treated at the CIRM Alpha Stem Cell Clinic at City of Hope (link) and will require a 28-day stay at or near the clinic.

Zaia expects to complete the 12-patient enrollment in about a year and he hopes that in the following months he will be able to report that the genetic manipulation worked and a significant portion of the blood forming stem cells have the altered gene and can pass it on to the T cells they make. Even though this will be a huge milestone, providing proof in principal that the therapy may work, he is already thinking about ways to make the process more efficient and less time consuming. The current process would be difficult to rollout to large-scale therapy. But he says “it is doable” to make an approach that could be widely available.

In this video HIV advocate and CIRM board member Jeff Sheehy looked forward to the launch of this trial when CIRM began the preclinical part of the project five years ago.

In this video HIV advocate and CIRM board member Jeff Sheehy looked forward to the launch of this trial when CIRM began the preclinical part of the project five years ago.

CIRM recently funded Paula Cannon at the University of Southern California—who worked with Zaia in the lead-up to this first trial—to develop a next generation of the gene editing process. She hopes to find a way to use the molecular scissors directly in patients rather than having to harvest their stem cells from their bone marrow, alter them in the lab and then infuse them back into the patient. Each of those steps causes inefficiency and the loss of cells and Zaia hopes that the possibility of doing the genetic manipulation directly in patients might be the ultimate way to go.

[Always wanting to take multiple shots on goal when we are dealing with a disease like HIV, CIRM funds a team at Calimmune also aimed at conferring immunity against HIV. The Calimmune therapy targets both the production of the CCR5 that the virus needs to enter cells and a viral fusion step. This dual approach has been shown to be effective against broad strains of HIV in pre-clinical studies. The company began a clinical trial in June 2013 and hopes to report results in 2016.]

One patient’s quest for something better

Antiretroviral therapy does a great job knocking down HIV in the body, look where it has gotten us! However, it’s not perfect and is not globally accessible with large segments of patients even in developed countries like the U.S. not receiving adequate therapy.

Mathew Sharp, right, with Timothy Brown, the "Berlin Patient" whose stem cell transplant for leukemia proved a gene variant on the surface of T cells could effectively cure HIV.

Mathew Sharp, right, with Timothy Brown, the “Berlin Patient” whose stem cell transplant for leukemia proved a gene variant on the surface of T cells could effectively cure HIV.

I have been a big proponent of antiretroviral therapy, even though it took me 15 years to finally construct a regimen that got me to undetectable virus levels. But the drugs never restored my T cells to normal.

After taking the drugs for so many years I have become tired of taking twice-daily dosing. I find myself missing doses. While my doctor and I are trying to construct a once-a-day regimen, it may become impossible for me with my particular viral strains.

I enrolled in a gene therapy trial for people who were stable on therapy but had never achieved higher T cells counts. After one infusion of a new technology called zinc-finger nuclease developed by Sangamo, I was able to double my T cells and they have remained that way for five years. But that therapy targeted adult T cells, not the stem cells of the current trial and as a result I have had to remain on antiviral therapy.

My outcome is great but with current research the hope is that scientists can even cure HIV so that no virus remains in the body and patients can stop antiviral meds. I remain hopeful that someday I will no longer have to be reminded that I have AIDS with my twice-daily dose, and be cured.

People with HIV deserve a cure. Despite effective antiretroviral therapy we live with a “persistent” virus that continues to affect our immune systems and may affect the aging process, significantly reducing life spans.

I am 58 years old and I worry that despite my current good health, complications related to viral persistence that are today killing people with HIV, may very well be my demise.

Mathew Sharp

Stem cell stories that caught our eye: Spinal cord injury, secret of creating complex tissue, mini brains in a dish and funding

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Monkey trial provides some hope for spinal cord injury. Stem cell treatments have made many mice and rats walk again after spinal cord injury, but moving from those rodents to human has been a slow process. Their immune systems and nervous systems are very different from ours. So, it was good to read this week that a team at Japan’s Keio University reported success in monkeys with systems much more like ours.

The experiment was “controlled.” They compared treated and non-treated animals and saw a significant difference in mobility between the two groups. Bloomberg picked up the release from the journal that published the work Stem Cells Translational Medicine, which quoted the study author Hideyuki Okano:

“An animal in the control group, for example, could not raise her hands up to head height at 12 weeks after injury when motor function almost plateaus. On the other hand, at the same point in time a transplanted animal was able to jump successfully and run so fast it was difficult for us to catch her. She could also grip a pen at 3 cm. above head-height.”

But the work requires some caveats. They treated all animals at exactly 14-days post injury, a window considered optimal for having initial inflammation subside and scar tissue not yet formed. Also, the researchers inflicted bruises not more severe damage to the spinal cord. Most patients with spinal cord injury are chronic, long past the 14-day window, and have damage to their spinal cords more severe than these animals.

The researchers started with embryonic stem cells and matured them into nerve progenitor cells, which they injected into the monkeys. While this process can yield plentiful cells for therapy the researchers acknowledged that much more research is needed before they can help the vast majority of spinal cord injuries with more severe and older injuries. CIRM funds a clinical trial using cells derived from embryonic stem cells to treat more complex spinal injuries, but it is just getting underway.

Clues to creating complex tissues. These days getting stem cells to form a single type of tissue, nerve or skin for example, is almost routine, with the remaining hurdle being purity. But getting stem cells to form complex tissues with multiple types of cells, while done a few times, still gets folks attention. For the most part, this is because we don’t know the cell-to-cell interactions required to form complex tissues. A CIRM-funded team at the University of California, San Diego, thinks they have part of the answer.

They studied something called the neurovascular unit, made up of blood vessels, smooth muscle and nerves that regulate heart rate, blood flow and breathing, among other basic functions. Using a lab model they showed how the different cell types come together to form the vital regulatory tissue. San Diego Newscape posted a piece on the work, quoting the study’s senor author David Cheresh:

“This new model allows us to follow the fate of distinct cell types during development, as they work cooperatively, in a way that we can’t in intact embryos, individual cell lines or mouse models. And if we’re ever going to use stem cells to develop new organ systems, we need to know how different cell types come together to form complex and functional structures such as the neurovascular unit.”

And a brainy example.   Prior research has created small brain “organoids” that started with stem cells and self assembled in a lab dish to create layers of nerves and support cells, but the cells did not interact much like normal brain tissue. Now, a team at Stanford has developed “cortex-like spheroids” with different types of cells that talk to each other.

Nerves and supporting cells form layers and organize like in the developing brain

Nerves and supporting cells form layers and organize like in the developing brain

In the new cortex spheres the nerves are healthier with a better network of the natural supporting cells called glial cells. The cells form layers that interact with each other like in our brains as we are developing.

A program at the National Institutes of Health (NIH) focusing on using stem cells to create models of disease in the lab funded the work. Thomas Insel, Director of the NIH’s National Institute of Mental Health described the importance of the current work in a press release from the institute picked up by HealthCanal:


“There’s been amazing progress in this field over the past few years. The cortex spheroids grow to a state in which they express functional connectivity, allowing for modeling and understanding of mental illnesses. They do not even begin to approach the complexity of a whole human brain. But that is not exactly what we need to study disorders of brain circuitry.“

The release starts with a fun lede imagining the day when a patient tormented by mental illness could have a model of their disease grown in a dish and researchers could genetically engineer better brain circuits for the patient. Certainly not just around the corner, but not far fetched.

States economic gain from funding research. The very niched web cite Governing posted a piece that appears to be largely from a conference in Washington D.C. hosted by the Greater Phoenix Economic Council. It quotes several experts speaking about the opportunity for states to gain economic advantage by funding research.

The piece notes some well documented examples of federal government spending on research spawning industries—think Silicon Valley. Then it talks about some more recent state examples including the California initiative that created CIRM.

One speaker, Mark Muro of the Brookings Institute said that we are in a new era now and states may not be able to fund research through their general tax revenue. He said:

“It may be the state becoming part of a consortium or working with Fortune 500 companies, or going to voters with a general obligation bond vote. I think we’re heading for a new complexity.”

Since CIRM was created through a vote for bonds, guess we have to agree.