Human satellite cells as cell therapy for the treatment of muscle waisting disorders
There is a tremendous medical need for the treatment of muscle waisting disorders such as muscular dystrophies or local muscle atrophies (e.g. in urinary incontinence or ventilator-induced diaphragm dysfunction). Various cell-based approaches are currently pursued but generation of skeletal muscle fibers starting either from myoblasts or iPSC as a source of myogenic cells are still challenging. Satellite cells are stem cells of the skeletal muscle. They display an enormous potential for self-renewal and regeneration of skeletal muscle tissue and are thus indispensable for muscle generation. These primary human muscle stem cells can be found in low abundance in a specific stem cell niche of skeletal muscle and ex-vivo culturing and expansion is very difficult. Nevertheless, autologous satellite cells are a perfect source for a cell product aiming to regenerate muscle fibers.
A) Significant enrichment of pure myogenic cells after ht. B) HMFFs transplanted after ht result in large human myofibers containing human nuclei.
The technology provides an efficient method to generate muscle fibers from satellite cells based on human muscle fiber fragments (HMFFs) which are obtained routinely by biopsy. Special culture conditions and hypothermic treatment (ht) result in significant enrichment and expansion of satellite cells associated to HMFFs. The method allows expansion of PAX7 muscle stem cells up to billions while the stem cell character is maintained. Human muscle stem cells obtained by this method can be transplanted in an in vivo model where they generate muscle fibers and repopulate their stem cell niche. Currently, the manufacturing process is adapted to GMP standards, a preclinical testing plan is established and a clinical phase I study for a first indication is planned. This method allows the use of autologous satellite cells, reducing the risk for immunogenic effects, and enables also for long-term storage of this rare cell type. As a further application, these primary muscle stem cells can be an interesting source for screening approaches in drug discovery.
Available for licensing or co-development
Patent applications pending in EP, US and JP basing on WO2016/030371, priority from August 25, 2014.
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Mol Ther Nucleic Acids. 2016 Jan 19;5:e277.