A Mount Sinai researcher has been awarded a five-year, $2.2 million grant from the National Institutes of Health (NIH) to expand skeletal muscle stem cells in culture, work that could someday be used to treat skeletal muscle injuries, sarcopenia, muscular dystrophy, and other muscle injuries and disorders.
The researcher, Woojin Han, PhD, is an Assistant Professor in the Leni and Peter W. May Department of Orthopedics at the Icahn School of Medicine at Mount Sinai. He plans to engineer an asymmetric designer hydrogel for expanding self-renewing muscle stem cells ex vivo by directing cellular polarity, which regulates how stem cells divide to make more stem cells or differentiate to give rise to new muscle fibers, a turning point known as stem cell fate specification.
The NIH's Stephen I. Katz Early Stage Investigator Research Project Grant supports an innovative project in an area of science that represents a change in research direction for an early-stage investigator and for which no preliminary data exist.
"We are very honored and excited to receive this award," said Dr. Han. "Muscle stem cell transplantation has potential to treat muscle trauma and diseases, including Duchenne muscular dystrophy and cancer cachexia. But limited cell source remains a tremendous challenge for its translation into practice. This five-year grant will allow us to better understand how muscle stem cells interact with their asymmetric microenvironment using bioengineered materials, and to engineer a cell manufacturing platform that mimics the native niche for expanding these cells for cell therapy applications."
Skeletal muscle stem cell transplantation is emerging as a promising strategy for treating muscle-associated disorders and orthopedic trauma, such as sarcopenia or open fractures often seen in car accidents, combat soldiers, or surgical resections. However, their scarcity limits their therapeutic potential. The inability to maintain and expand these cells ex vivo further compounds this challenge. Therefore, there is a critical need for a strategy to maintain and expand therapeutically potent muscle stem cells ex vivo long-term.
To date, muscle stem cell culture systems do not exist that recapitulate the asymmetric niche, consisting of myofiber and basal lamina, required to establish cellular polarity, support physiologic cell division, and guide fate specification. The contribution of active mechanical forces in modulating muscle stem cell polarity, division, and fate specification also remains overlooked.
"We are deeply honored to receive the generous support of the NIH and I am very excited to work with Dr. Han on this project," said Robert Krauss, PhD, Mount Sinai Professor in Cell Biology and co-investigator on the study. "Dr. Han's bioengineering approaches to muscle stem cell biology will provide important new information about how tissues regenerate, and he is highly deserving of the prestigious NIH Stephen Katz Early Stage Investigator Award."
"Receiving this level of support from the NIH is a remarkable accomplishment," said Leesa Galatz, MD, Mount Sinai Professor and Chair of Orthopedic Surgery at Icahn Mount Sinai and the Mount Sinai Health System. "Dr. Han's pioneering study will provide fundamental knowledge on stem cell fate specification, and his deep expertise in biomaterials and muscle stem cell biology is bound to set him up for success."
"The Department is thrilled that Dr. Han is among the first NIH Katz award recipients, which distinguishes him nationally as a rising star in musculoskeletal research," said James Iatridis, PhD, Professor and Vice Chair for Research in the Department of Orthopedics. "Dr. Han's research involves collaborations with cell biologists and shoulder surgeons, and his fundamental discoveries can be applied to engineer novel therapies to improve outcomes of orthopedic surgery patients such as those with rotator cuff injuries."
