Path from Bench-to-Bedside: iPS Cell Therapy for Muscular Dystrophies


Non-Gene Targeting Therapies

Poster Number: 124


Rita Perlingeiro, PhD, Alessandro Magli, David McKenna


1. University of Minnesota

Pluripotent stem (PS) cells represent an attractive cell source for the treatment of muscular dystrophies since they allow for the generation of virtually unlimited numbers of myogenic progenitors. Our laboratory has demonstrated that efficient generation of skeletal myogenic progenitors from human PS cells is possible using controlled expression of the transcription factor PAX7. Transplantation studies show that cells produced with this approach produce functional muscle. Following identification of ICAM1 (also known as CD54), Integrin α9β1 and Syndecan 2 as markers defining human myogenic progenitors from PAX7-induced differentiating PS cell cultures, we have recently focused on the generation of a clinical-grade product. This process requires a careful systematic optimization of the manufacturing process to ensure the maintenance of the product key biological features, patient safety, and compliance with current good manufacturing practices (cGMP). We determined the optimal media components ensuring efficient in vitro expansion/differentiation and in vivo muscle regeneration capacity. Furthermore, we identified the conditions enabling effective and cost-efficient purification of human myogenic progenitors and used this information to scale-up our cell manufacturing process using the cGMP-compatible CliniMACS® system. Lastly, as the PAX7-inducible system involves lentiviral transduction of PS cell cultures, we began investigating lentiviral integration sites to minimize the risk of positional integration effects. Altogether, these studies are defining the optimal efficient path for the cGMP manufacturing of human PS cell-derived myogenic progenitors, which we hope will pave the way for a First-in-Human Clinical Trial for muscular dystrophy patients.