Researchers find that different stem cells are responsible for the repair of different kinds of bone injuries: Newsroom





DALLAS – October 21, 2022 – New research from the Children’s Medical Center Research Institute at UT Southwestern (CRI) has found that different populations of skeletal stem cells (SSCs) contribute to the repair of different types of bone damage. In the study published in Cell Stem Cell, the researchers identified distinct cellular markers that allowed them to track SSCs in the bone marrow inside the bones versus SSCs in the periosteum on the outer surface of the bones. They found that while bone marrow SSCs are responsible for the continued production of bone cells in normal bones and for the repair of certain bone injuries, periosteal SSCs are primarily responsible for fracture repair.

Sean Morrison, Ph.D.

SSCs must generate new bone cells throughout life to maintain and repair the skeleton. The skeleton is unusual in that it has several types of stem cells that reside in different regions of the bone, including the bone marrow and the periosteum. After bone injuries, such as fractures, SSCs in the bone marrow and periosteum begin to proliferate but make very different contributions to bone repair. Researchers in the Morrison lab have found that bone marrow SSCs repair smaller, stabilized bone lesions and are responsible for new bone growth under normal conditions in adulthood. In contrast, periosteal SSCs are primarily responsible for repairing larger, unstabilized injuries such as fractures. Surprisingly, the researchers also found that periosteal SSCs not only regenerate bone, but also bone marrow cells at the fracture site, giving rise to new bone marrow SSCs.

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“The discovery that different bone-forming stem cells are responsible for different aspects of bone maintenance and repair will allow us to focus future bone regeneration efforts on the right stem cell population,” said Sean Morrison, Ph. .D., director of the CRI. and a researcher from the Howard Hughes Medical Institute.

Fractured mouse tibia undergoing repair by Gli1+ periosteal skeletal stem cells (red).

Historically, the contributions of bone marrow versus periosteum SSCs to bone repair have been debated, in part because few markers were available to distinguish these cell populations. To overcome this hurdle, postdoctoral researcher Elise Jeffery, Ph.D., systematically compared 11 lines of genetically modified mice that were previously used to label bone-forming cells to identify markers that could distinguish periosteal SSCs from SSCs bone marrow. They found that periosteal SSCs were marked by a signaling protein called Gli1, while bone marrow SSCs were marked by the leptin receptor and adiponectin. These results are consistent with previous research from the Morrison lab which found that leptin receptor-positive bone marrow SSCs are a major source of new osteoblasts for bone maintenance and repair.

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“The results of this study open up several new avenues of research into the signals that activate different types of skeletal stem cells in response to bone injury. We hope to exploit this information to ultimately adapt the treatment of patients according to their type of bone lesion and to identify new therapeutic targets that promote fracture healing. said Damon Runyon Foundation Postdoctoral Fellow Dr. Jeffery.

Dr. Morrison is a professor in CRI and the Department of Pediatrics at UT Southwestern, a Cancer Prevention and Research Institute of Texas (CPRIT) researcher in cancer research, and a member of the National Academies of Science and Medicine. He also holds the Kathryne and Gene Bishop Distinguished Chair in Pediatric Research at UT Southwestern’s Children’s Research Institute and the Mary McDermott Cook Chair in Pediatric Genetics.

This research was funded in part by the Josephine Hughes Sterling Foundation, the Damon Runyon Cancer Research Foundation and donors from the Children’s Medical Center Foundation.

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About IRC

CRI is a joint venture of UT Southwestern Medical Center and Children’s Medical Center Dallas, the flagship hospital for children’s health. CRI’s mission is to perform transformative biomedical research to better understand the biological basis of disease. Located in Dallas, Texas, CRI is home to interdisciplinary groups of scientists and physicians pursuing research at the interface of regenerative medicine, cancer biology, and metabolism. For more information, visit cri.utsw.edu. To support CRI, go to give.childrens.com/about-us/why-help/cri/.

About UT Southwestern Medical Center

UT Southwestern, one of the nation’s leading academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes and includes 24 members of the National Academy of Sciences, 18 members of the National Academy of Medicine, and 14 researchers from the Howard Hughes Medical Institute. Full-time faculty of more than 2,900 are responsible for groundbreaking medical advances and committed to rapidly translating scientific research into new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 100,000 inpatients, more than 360,000 emergency room cases, and oversee nearly 4 million outpatient visits annually.



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