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Progress Report: Xenotransplanation of Human Muscle

Posted by George Shaw on January 31, 2017

Maura H Parker PhD

The long-term goal of my work is to expand human muscle progenitor cells in culture, and transplant these cells into a mouse muscle in order to replace that muscle with a human FSHD affected muscle. This idea is based on successful expansion and transplant of canine muscle progenitor cells, resulting in near full replacement of a mouse muscle with canine muscle. However, expanding human muscle-derived cells in the same way we expanded canine muscle-derived cells failed to generate cells that could engraft into mouse muscle. We hypothesized that this was due to the culture conditions, and proposed to generate a high throughput system to analyze the effects of changing culture conditions and adding small molecules.

Specifically, we proposed that if we could monitor expression of Pax7 and MyoD, we could determine which conditions maintain Pax7 expression and inhibit MyoD expression. This is based on results from canine and mouse cells that indicate that muscle progenitor cells are Pax7-positive and MyoD-negative. Unfortunately, there have been many insurmountable obstacles. One of the biggest problems is that human cells lose Pax7 expression during culture, in stark contrast to canine and mouse muscle progenitors. This has forced us to step back and ask some basic questions about the cells we have isolated from the human muscle, and how these cells are behaving in response to our culture conditions. Once we can answer these questions, we hope to have a better idea of how to modify the cell isolation procedure and the culture conditions, and be able to expand human muscle progenitor cells for transplant.

See grant: Optimizing expansion of human muscle stem cells for transplant into mice.