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August 2, 2021
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Scientists have known that cellular reprogramming could reverse the aging process in mesenchymal stem/ stromal cells (MSCs), but the underlying mechanisms have not been clear. Newly reported research by scientists at the University of Wisconsin-Madison has identified a key role for the protein GATA6 in the aging reversal process.
“While agreeing with previous findings in MSC rejuvenation by cellular reprogramming, our study goes further to provide insight into how reprogrammed MSCs are regulated molecularly to ameliorate the cellular hallmarks of aging,” explained lead researcher, Wan-Ju Li, Ph.D., a faculty member in the Department of Orthopedics and Rehabilitation and the Department of Biomedical Engineering. “We believe our findings will help improve the understanding of MSC aging and its significance in regenerative medicine.”
Li and colleagues used cellular reprogramming to establish a genetically identical young and old cell model. They began by isolating MSCs from human synovial fluid (SF-MSCs) and reprogrammed them into induced pluripotent stem cells (iPSCs). Then they reverted these iPSCs back to MSCs, in effect rejuvenating the MSCs. “When we compared the reprogrammed MSCs to the non-rejuvenated parental MSCs, we found that aging-related activities were greatly reduced in reprogrammed MSCs compared to those in their parental lines. This indicates a reversal of cell aging,” Li said.
“Overall, we were able to demonstrate that SF-MSCs undergo substantial changes in properties and functions as a result of cellular reprogramming,” Li said. “These changes in iPSC-MSCs collectively indicate the amelioration of cell aging. Most significantly, we were able to identify the GATA6/SHH/FOXP1 signaling pathway as an underlying mechanism that controls cell aging-related activities.”
The authors concluded, “Our results, while agreeing with previous findings in MSC rejuvenation by cellular reprogramming, provide insight into how reprogrammed MSCs are regulated molecularly to ameliorate cellular hallmarks of aging … These findings, critical to enhancing the knowledge of MSC senescence and diseases associated with MSC aging and to providing insight into developing pharmacological strategies to ameliorate cellular aging, are considered significant and timely for regenerative medicine.”
ARTICLE: JOSEPH MODICA
SCIENCE/HEALTH EDITOR: KYLE SMITH