PDGFRα-positive cells in bone marrow are mobilized by high mobility group box 1 (HMGB1) to regenerate injured epithelia
The role of bone marrow cells in repairing ectodermal tissue, such as skin epidermis, is not clear. To explore this process further, this study examined a particular form of cutaneous repair, skin grafting. Grafting of full thickness wild-type mouse skin onto mice that had received a green fluorescent protein-bone marrow transplant after whole body irradiation led to an abundance of bone marrow-derived epithelial cells in follicular and interfollicular epidermis that persisted for at least 5 months. The source of the epithelial progenitors was the nonhematopoietic, platelet-derived growth factor receptor α-positive (Lin−/PDGFRα+) bone marrow cell population. Skin grafts release high mobility group box 1 (HMGB1) in vitro and in vivo, which can mobilize the Lin−/PDGFRα+ cells from bone marrow to target the engrafted skin. These data provide unique insight into how skin grafts facilitate tissue repair and identify strategies germane to regenerative medicine for skin and, perhaps, other ectodermal defects or diseases.
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Professor John McGrath, Head of the Genetic Skin Disease Group at King's, recently spent several months working on the project in Osaka. He said: "This work is tremendously exciting for the field of regenerative medicine. The key achievement has been to find out which bone marrow cells can transform into skin cells and repair and maintain the skin as healthy tissue, and to learn how this process happens.
"Understanding how the protein HMGB1 works as a distress signal to summon these particular bone marrow cells is expected to have significant implications for clinical medicine, and could potentially revolutionise the management of wound healing.
"Chronic wounds and tissue injury represent a significant cost to the NHS, not to mention the debilitating effects on peoples' quality of life. Our plan is to see if we can now use this scientific advance to develop more effective treatments to improve tissue repair in skin and perhaps other organs."
Professor McGrath is working together with colleagues at Osaka University to harness the key parts of the HMGB1 protein to create a drug treatment that can augment tissue repair. It is expected that the developed treatment will be tested in animal models in about a year and enter clinical trials shortly afterwards.
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