Wednesday, November 6, 2019, 5:30pm to 7:30pm
HMS, Armenise 108 (210 Longwood Ave, Boston)
A novel cell therapy platform for the treatment of skeletal muscle conditions
Dr. Feodor Price and Dr. Lee Rubin
Department of Stem Cell and Regenerative Biology
Conditions resulting in abnormal skeletal muscle function affect millions worldwide and many, such as muscular dystrophies, neuromuscular diseases, and acute muscle trauma lack treatment options. To date, all cell therapy targeting muscular afflictions have been conducted using highly passaged myoblasts to restore skeletal muscle function. Satellite cells, the canonical skeletal muscle stem cell, upon activation, can rapidly proliferate and differentiate into myoblasts; however, there has not been success to culture satellite cells in vitro or to expand them to clinically relevant levels.
To overcome this challenge, the Rubin lab has developed a novel method to dramatically expand myogenic cells from a single patient muscle biopsy. These in vitro derived satellite cells (idSCs) are transcriptionally analogous to and behave like satellite cells when transplanted in vivo and can produce cells that engraft and fuse into myofibers and more importantly have the capacity to repopulate the satellite cell niche within skeletal muscle.
idSCs provide four significant therapeutic benefits compared to current myoblast transplantation protocols: (i) increased cell engraftment; (ii) repopulation and self-renewal of the satellite cell niche; (iii) persistence following multiple rounds of muscle injury and regeneration and (iv) a greater radius of function beyond the site of injection. Furthermore, when endogenous satellite cells are incapacitated idSC treated samples exhibit functional improvement in muscle force capacity, whereas this is not observed in similar experiments conducted with myoblasts.
Based on this data, we envision the use of idSCs as a broadly applicable and novel cell therapy that can be long-acting or curative for localized muscle loss or even muscle degenerative diseases. In summary, prior clinical trials have failed due to the use of the wrong muscle cell (myoblasts) rather than satellite cells. Furthermore, certain indications present more tractable models for treatment with a skeletal muscle cell therapy. Namely these indications involve an autologous local delivery of cells to be successful. Several muscle conditions satisfy these criteria including acute trauma, incontinence and oculopharyngeal muscular dystrophy.
Harvard University patent applications pending covering idSCs and methods for producing idSCs