Living Progenitor Cells Edge Closer to “Cure-all” Status

Living progenitor cells, often misnamed “Stem Cells,” have been put forward as potential treatments for a wide variety of indications. Unfortunately, in most of those cases, scientifically robust data does not exist.

With regards to COVID-19, however, level one clinical studies conducted by top labs, have found that they may be beneficial for patients suffering from COVID-19 and, when combined with other recent studies, that such living progenitor cell treatments may be closer to broad application status.

Named the “Breakthrough of the Year” by Science in 1999, claims of the uses of stem cells abounded, with promises of cures for Duchenne’s muscular dystrophy (which only this year has seen some success in early trials of gene therapies) to restoring feeling and movement in patients with paralysis from spinal cord injuries. As with most scientific breakthroughs, early understanding usually leads to ambitious timelines and overpromised successes (for example, a cure for cystic fibrosis was promised within a few short years after identifying the gene responsible in 1989. Research toward a cure is still on going, over 30 years later). Only recently are we seeing benefits from stem cell research, and due to the unregulated nature of the treatments, it is difficult to tease out the efficacy.

Before the U.S. FDA clamped down on some stem cell clinics in 2017, the treatments were used, without substantial evidence of safety or efficacy, for just about anything. The FDA took action in 2017 to close down some stem cell clinics offering “cures” for amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), macular degeneration, Parkinson’s disease, and more after three patients who were treated for macular degeneration were left blinded. Hopefully, the FDA will continue to exert pressure on clinics to, at the very least, encourage proper handling of the cells to prevent infection, but to also strive toward using the products for evidence-based therapies.

In orthopedics, several options are currently available to provide cell-based therapies to patients. The primary options include platelet-rich plasma (PRP), and bone marrow aspirate concentrate (BMAC). Both of these treatments involve extracting autologous tissue samples (blood or iliac crest bone marrow), concentration and extraction of cellular components and reinjection to the treatment site. PRP is a relatively inexpensive process, which costs about $700, while a BMAC preparation costs in order of magnitude more. Both treatments are considered investigational and are not covered by insurers, so they are typically reserved for patients with the desire and means to pay out-of-pocket. The first FDA approved cellular therapy for orthopedic use is MACI from Vericel. The therapy requires extraction and shipment of a sample of the patient’s knee cartilage to the company which expands and cultures the cells in a porcine collagen membrane. The final product is then shipped to the surgeon for implantation in a second procedure.

Living Cells for Non-Fusion Treatment of Degenerative Disc Disease

Orthopedics This Week spoke with surgeon, Andrew Bulczynski M.D., at DISC Sports and Spine in Southern California. Bulczynski is a believer in PRP and BMAC for his patients and has found that injections of the cells are much more effective for long-term treatment for certain ailments that were previously limited to analgesic or steroid injections. He has found that patients who he previously would have given a cortisone injection, which he limited to only a couple of injections due to the catabolic effects of the drug, come back less often or never again after a PRP treatment. He considers himself an optimistic skeptic, along with the rest of the practice, who are focused on outcomes data for the newer treatments. He sees the benefits for some patients, and thinks that the risk profile is much better than other options, so there is little reason to withhold the treatments.

Bulczynski described his experience with the Vericel MACI treatment as having improved significantly with updates to the process. Early on, it was “very procedure dependent,” he said, explaining that the seeding of the expanded cells required placement of a membrane autograft to hold the cells in place. Now, incorporation of the chondrocytes in a collagen matrix has made the process very easy for just about any surgeon to perform.

In addition to PRP and BMAC, both considered autogenic cellular products, there are a number of allogenic products on the market, or in trials. Live-cell allogenic bone grafts are available for spinal fusion, but data on the efficacy, or even the cellular viability is sparce. DiscGenics, Inc., a company specializing in “discogenic” cells for treating degenerative disc disease (DDD), is currently testing its cellular product in patients in the U.S. and Japan. The company recently raised $50 million in Series C financing to continue funding its ongoing clinical trials.

Mesoblast Ltd. is one company that has invested heavily in the notion that stem cells really are a cure-all. It currently has multiple ongoing clinical trials that are investigating the use of its mesenchymal stem cells (MSC). The MSCs are being investigated for the treatment of degenerative disc disease, acute graft vs host disease in children, acute respiratory distress syndrome (ARDS) due to COVID-19, and more. The company has recently seen positive reactions from the U.S. FDA with a 9-to-1 committee decision in favor of its therapy for pediatric graft vs. host disease, which bodes well for other applications of the same, or similar cells.

Mesoblast Chief Medical Officer Fred Grossman, D.O. said of the ongoing Phase 3 trial of the MSCs for DDD, “Key to the mechanism of action of Mesoblast’s mesenchymal lineage cells is their ability to be activated by and then counter severe inflammation. It is recognized that inflammation plays a key role in the development of chronic low back pain accompanying degenerative disc disease, and the multi-modal mechanism of action of our mesenchymal precursor cell product candidate MPC—60-ID could represent a fundamental advantage over other therapies. The Phase 3 randomized controlled trial in 404 patients is due to read out soon, and we  are eager to see whether these data replicate the results of a Phase 2 trial of 100 patients, where a single intra-discal injection of MPC-06-ID resulted in meaningful and durable improvements in pain intensity and functionality for up to three years.”

As mentioned by Grossman, a key to stem cells is their ability to reduce inflammation. Early trials by Mesoblast for treating ventilator-dependent COVID-19 patients suffering from ARDS found up to 83% survival compared to as low as 12% survival for those treated with the standard of care, as of April 2020. The anti-inflammatory properties are sought after for treating DDD, graft vs. host disease, and treating the worst effects of COVID-19. Mesoblast is far from the only entity researching the use of stem cells for treating COVID-19; universities, research institutes, and companies, alike, are testing an array of stem cell-based therapies on patients suffering from COVID-19 with trials at various stages of progress.

COVID-19, even with a vaccine approved next year, is likely to continue to inflict severe symptoms on newly infected people for years to come and continue to maintain a market for an effective treatment for a considerable time. The influx of funding due to COVID-19 research initiatives will likely have ripple effects in the world of stem cell research, potentially accelerating the development of stem cell therapeutics for countless other maladies.