At a recent symposium of cellular therapies held by the Department of Pediatrics, we noticed something. Scientists do not have consistent language to talk about a type of cells called “mesenchymal stem cells” or “mesenchymal stromal cells.” Within the same symposium, some researchers used the first term, and others used the second.
Guest speaker Joanne Kurtzberg from Duke discussed the potential use of MSCs to treat autism spectrum disorder, cerebral palsy, and hypoxic-ischemic encephalopathy. Exciting stuff, although the outcomes of the clinical studies underway are still uncertain. In these studies, the mesenchymal stromal cells (the language Kurtzberg used) are derived from umbilical cord blood, not adult tissues.
Nomenclature matters, because a recent editorial in Nature calls for the term “stem cell” not to be used for mesenchymal (whatever) cells. They are often isolated from bone marrow or fat. MSCs are thought have the potential to become cells such as fibroblasts, cartilage, bone and fat. But most of their therapeutic effects appear to come from the growth factors and RNA-containing exosomes they secrete, rather than their ability to directly replace cells in damaged tissues.
The Nature editorial argues that “wildly varying reports have helped MSCs to acquire a near-magical, all-things-to-all-people quality in the media and in the public mind,” and calls for better characterization of the cells and more rigor in clinical studies.
At Emory, gastroenterologist Subra Kugathasan talked about his experience with MSCs in inflammatory bowel diseases. Hematologist Edwin Horwitz discussed his past work with MSCs on osteogenesis imperfecta. And Georgia Tech-based biomedical engineer Krishnendu Roy pointed out the need to reduce costs and scale up, especially if MSCs start to be used at a higher volume.
Several of the speakers were supported by the Marcus Foundation, which has a long-established interest in autism, stroke, cerebral palsy and other neurological conditions.
Basic research presentations at 2016 American Heart Association Scientific Sessions: cell therapy for heart attack (mesenchymal stem cells) in animal models and role of CD73, gradual release drug for atrial fibrillation, how particles from stored blood affects blood vessels.
Mesenchymal Stem Cells Require CD73 Activity to Reduce Leukocyte Associated Inflammation Following Myocardial Ischemia-Reperfusion Injury
Nov.13, 1:30 pm, Science and Technology Hall- Basic Science Theater
Cell therapy, using the patient’s own cells to reduce damage to the heart after a heart attack, has been a hot topic. Mesenchymal stem cells are derived from the bone marrow and can’t replace heart muscle. But they do exert anti-inflammatory and anti-oxidative effects, Eric Shin, MD, Rebecca Levit, MD and colleagues show in a rat model of heart attack.
The researchers use the gel material alginate to encapsulate the cells, in a way previously described by Levit. They say this is the first study to demonstrate that mesenchymal stem cells reduce reactive oxygen species production in the heart. and that the molecule CD73, which degrades ATP/ADP into adenosine, is needed for the anti-inflammatory effect. CD73 is also a cancer immunotherapy target. Read more
Emory neurosurgeon Robert Gross was recently quoted in a Tennessee newspaper article about a clinical trial of cell therapy for stroke. He used cautionary language to set expectations.
“We’re still in the very early exploratory phases of this type of work,” Gross told the Chattanooga Times Free Press. “In these cases, a significant area of the brain has been damaged, and simply putting a deposit of undifferentiated cells into the brain and magically thinking they will rewire the brain as good as new is naive. None of us think that.”
A more preliminary study (just 18 patients) using the same approach at Stanford and University of Pittsburgh was published this summer in Stroke, which says it was the “first reported intracerebral stem cell transplant study for stroke in North America.” The San Diego Union Tribune made an effort to be balanced in how the results were described:
Stroke patients who received genetically modified stem cells significantly recovered their mobility… Outcomes varied, but more than a third experienced significant benefit.
The newspaper articles made us curious about what these cells actually are. They’re mesenchymal stromal cells, engineered with an extra modified Notch gene. That extra gene drives them to make more supportive factors for neurons, but it doesn’t turn them into neurons. Read more
Patients with heart failure who received an experimental stem cell therapy experienced a reduced rate of death, hospitalization and unplanned clinic visits over the next year compared to a placebo group, according to results presented Monday at the American College of Cardiology meeting in Chicago.
The results of the ixCELL-DCM study were published online Monday by The Lancet. It was reportedly the largest cell therapy study done in patients with heart failure so far (58 treated vs 51 placebo).
Emory University School of Medicine investigators led by Arshed Quyyumi, MD, and their patients participated in the study, and Emory was one of the largest enrolling sites. Lead authors were Timothy Henry, MD of Cedars-Sinai Heart Institute in Los Angeles and Amit Patel, MD of the University of Utah.
â€œFor the first time, a clinical trial has shown that administration of a cellular therapeutic results in an improvement in cardiac outcomes based on a prespecified analysis,â€ an editorial accompanying the paper in The Lancet says.
This study, which was sponsored by Vericel Corporation, was phase II, meaning that a larger phase III study will be needed before FDA approval. Read more
What applies to meat, vegetables and fish may also apply to cells for use in cell therapy: frozen often isn’t quite as good.
Ian Copland and colleagues from Emory’s Personalized Immunotherapy Center have a paper this week in Stem Cells Reports discussing how freezing and thawing stem cells messes them up. Specifically, it disrupts their actin cytoskeletons and impairs their ability to find their niches in the body. Culturing the cells for 48 hours after thawing does seem to correct the problem, though.
The findings have some straightforward implications for researchers planning to testÂ cell therapies inÂ clinical applications. The authors conclude:
Until such time as a cryopreservation and thawing procedure can yield a viable and fully functional MSC product immediately after thawing, our data support the idea of using live MSCs rather than post-thaw cryo MSCs for clinical evaluation of MSCs as an immunosuppressive agent.
Notably, the Emory Personalized Immunotherapy Center has built a process designed around offering never-frozen autologous (that is, the patient’s own)Â mesenchymal stem cells, as therapies for autoimmune disordersÂ such as Crohn’s disease.
Stem cell therapy for heart disease is happening. Around the world, thousands of heart disease patients have been treated in clinical studies with some form of bone marrow cells or stem cells. But in many of those studies, the actual impact on heart function was modest or inconsistent. One reason is that most of the cells either donâ€™t stay in the heart or die soon after being introduced into the body.
Cardiology researchers at Emory have a solution for this problem. The researchers package stem cells in a capsule made of alginate, a gel-like substance. Once packaged, the cells stay put, releasing their healing factors over time.
Researchers used encapsulated mesenchymal stem cells to form a â€œpatchâ€ that was applied to the hearts of rats after a heart attack. Compared with animals treated with naked cells (or with nothing), rats treated with the capsule patches displayed increased heart function, reduced scar size and more growth of new blood vessels a month later. In addition, many more of the encapsulated cells stayed alive. Read more