Feature Researcher: Rita Perlingeiro

December 1, 2017

Pluripotent stem cells represent an exceptionally potent source of tissue-specific progenitors for cell therapeutic applications. However, translation of basic science discoveries to the clinic involves key steps for ensuring patient safety.

With this in mind, Perlingeiro and colleagues recently published a study (Magli et al., Cell Reports, 19:2867, 2017) in which they systematically addressed several potential concerns affecting the production of human pluripotent stem cell-derived myogenic progenitors. The Perlingeiro team started with an in-depth molecular analysis of the process of human skeletal myogenic commitment. Gene expression profiling of human pluripotent stem cells undergoing PAX7-dependent myogenic differentiation coupled with identification of PAX7 binding sites by ChIP-seq clearly demonstrated the ability of this transcription factor to activate the skeletal myogenic program in early human mesodermal cells, evidence that so far had been limited to murine cells. Importantly, these analyses led to the identification of several PAX7 target genes, which serve as new myogenic stem cell surface markers: CD54, integrin α9β1 and SDC2. These reproducibly allow for the purification of myogenic progenitors using cGMP-compatible methods. Importantly, CD54+α9β1+SDC2+ myogenic progenitors are endowed with long-term in vivo regenerative potential.

This is a critical step toward the clinical translation of pluripotent stem cell-based therapy for skeletal muscle disorders. The Perlingeiro team, in collaboration with Dr. David McKenna, has just been awarded a grant from the U.S. Department of Defense to perform scalability and safety studies that will be instrumental for future generation of clinical-grade pluripotent stem cell-derived myogenic progenitors for the treatment of Duchenne and other types of muscular dystrophies.