# Preclinical studies of pluripotent stem cell-derived myogenic progenitors in non-human primates

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2021 · $605,497

## Abstract

Summary
Muscular dystrophies are genetically and clinically heterogeneous disorders characterized by progressive
weakness and degeneration of the skeletal muscles that control movement. The most common, Duchenne
Muscular Dystrophy (DMD), is caused by genetic and biochemical defects of the dystrophin-glycoprotein
complex (DGC). These alterations lead to cell membrane damage and death of muscle cells, resulting in chronic
tissue degeneration and impaired muscle contractility. Although no effective treatment is available at present,
one attractive therapeutic approach is to use cell-based therapies to promote muscle regeneration. There has
been tremendous excitement for the therapeutic potential of induced pluripotent stem (iPS) cells in treating
genetic diseases since these cells have virtually unlimited proliferation potential, and can differentiate into all cell
types. We have pioneered a method to generate engraftable skeletal myogenic progenitors from pluripotent stem
cells through conditional expression of Pax3 or Pax7. This approach results in highly efficient generation of
therapeutic myogenic progenitors, which when transplanted into dystrophic mice locally or systemically produce
large quantities of functional skeletal muscle tissue that incorporates normally into the host muscle. Importantly,
a fraction of transplanted cells remains mononuclear, and displays key features of skeletal muscle stem cells,
including satellite cell localization, response to re-injury, and contribution to muscle regeneration in secondary
transplantation assays. Based on these encouraging findings, we have begun the manufacturing of these cells
under cGMP compatible conditions and performed preclinical studies in murine recipients. The results from these
studies are promising but before moving this therapy towards clinical translation, it would be ideal to assess
scalability, delivery, distribution, safety, and engraftment in larger animal models. Therefore, here we propose
preclinical studies to investigate these parameters using non-human primates (NHP) as recipients. It will also be
critical to understand the impact of HLA mismatch on muscle engraftment, and NHP represent the ideal system
to properly address this question. The transplantation of NHP iPS cell-derived myogenic progenitors into NHP
recipients will provide critical knowledge for understanding tolerance in the allogeneic setting. This aspect, which
has important implications for regenerative medicine, has been mostly overlooked in the pluripotent stem cell
field. These are all critical prerequisites to advance this therapy towards successful clinical translation.

## Key facts

- **NIH application ID:** 10311166
- **Project number:** 1R01AR078624-01A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Melanie Lynn Graham
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $605,497
- **Award type:** 1
- **Project period:** 2021-08-06 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10311166

## Citation

> US National Institutes of Health, RePORTER application 10311166, Preclinical studies of pluripotent stem cell-derived myogenic progenitors in non-human primates (1R01AR078624-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10311166. Licensed CC0.

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