In order to increase the survival of stem cells in culture, research from Purdue University has shown that controlling the amount of oxygen to which the stem cells are exposed, can significantly increase the effectiveness of stem cell-based procedures to treat an often fatal form of muscular dystrophy.
Mutations in the dystrophin gene cause Duchenne muscular dystrophy (DMD). DMD causes the constant breakdown of muscles, and the gradual depletion of muscle-based stem cells that repair the damage and progressive muscle wasting that characterize this disease. Healthy stem cells divide and repair damaged muscles or other tissues. This is the basis of stem cell therapy, which is the implantation of healthy stem cells to repair degenerating or injured tissues. Stem cell therapies have shown promise against DMD and other neurodegenerative diseases, but a major caveat of these treatments is that few of the implanted stem cells survive the procedure.
Shihuan Kuang, a Purdue assistant professor of animal sciences, and Weiyi Liu, a postdoctoral research associate, have shown that the survival of implanted muscle stem cells is increased by as much as fivefold in a mouse model if the cells are cultured under oxygen levels similar to those found in human muscles.
“Stem cells survive in a microenvironment in the body that has a low oxygen level,” Kuang said. “But when we culture cells, there is a lot of oxygen around the petri dish. We wanted to see if less oxygen could mimic that microenvironment. When we did that, we saw that more stem cells survived the transplant.”
According to Liu, when stem cells are grown in higher oxygen levels, they adapt to those levels in order to acclimate to their surroundings. Therefore, when these same cells are injected into muscles with lower oxygen levels, they die from a lack of sufficient oxygen (in layman’s terms, they suffocate).
However, when the cells are grown in lower oxygen levels, they survive when transplanted into muscles. As Liu said, “By contrast, in our study the cells become used to the host environment when they are conditioned under low oxygen levels prior to transplantation.”
Their experiments were done in mice, and when transplanted into the skeletal muscles of DMD mice, Kuang and Liu saw more stem cells survive the transplants. Furthermore, those stem cells retained their ability to duplicate themselves.
“When we lower the oxygen level, we can also maintain the self-renewal process,” Kuang said. “If these stem cells self-renew, they should never be used up and should continue to repair damaged muscle.”
These studies were published in the journal Development, and this protocol shows promise as a strategy to increase the effectiveness of stem cell therapy for DMD patients. DMD occurs in about one in 3,500 boys, and symptoms being at about 3-5 years old. DMD confines almost all patients to wheelchairs by their 20s, is often fatal as muscles that control the abilities to breathe and eat deteriorate.
For future studies, Kuang’s lab will examine those signaling pathways within stem cells that are affected by low oxygen levels. They will determine if human muscle stem cells are similarly regulated by environmental oxygen.
This research was funded by the The National Institutes of Health, the Muscular Dystrophy Association and the U.S. Department of Agriculture funded the research.
Beyond the Dish 