Scientists have identified a rare subset of bone marrow cells involved in repairing damaged skin tissue together with the biochemical signal that calls the cells to the site of injury. The researchers, at Kings College and Osaka University, are already working to develop a drug based on the recruiting factor, which is called high mobility group box 1 (HMGB1), for potential applications in wound healing.
They hope to start in vivo preclinical testing in about a year and clinical trials shortly after that. Their work is published in PNAS in a paper titled “PDGFRα-positive cells in bone marrow are mobilized by high mobility group box 1 (HMGB1) to regenerate injured epithelia.”
Previous studies have identified bone marrow as a source of fibroblast-like cells in the dermiss and demonstrated that the number of these cells increases after skin damage, reports John McGrath, M.D., head of the genetic skin disease group at King’s College, and colleagues. Bone marrow can in addition generate keratinoncytes in the epithelia, but such cells are extremely rare in the epidermis, and their biological relevance and potential role in epithelial regeneration are not fully understood. In addition to this scientists have yet to identify both the type of bone marrow cells that give rise to keratinocytes and the mechanisms needed to trigger their recruitment to the site of repair.
To throw more light on the cell types and mechanisms that may be involved, Dr. McGrath teamed up in Japan with researchers at Osaka University. Their approach involved grafting full thickness wild-type mouse skin onto mice that had received a green fluorescent protein bone marrow transplant after whole body irradiation. This procedure led to an abundance of bone marrow-derived epithelial cells in both the follicular and interfollicular epidermis, which they discovered were derived from a non-ematopoietic, platelet-derived growth factor receptor α-positive (Lin−/PDGFRα+) bone marrow cell population. About 1 in 450 bone marrow cells is Lin−/PDGFRα+. The cells were mobilized from the bone marrow to the graft site by the release of high mobility group box 1 (HMGB1) into the blood at the site of damage.
“Here we have defined a subpopulation of cells that have the capacity to repair skin including epidermis," the authors conclude. "The Lin−/PDGFRα+ BM cell marker profile is not unique to one particular cell population, and our data suggests that it is shared by about 1 in 450 bone marrow cells.”
The concept that a particular threshold concentration of HMGB1 in serum is relevant to mobilizing the relevant bone marrow cells and targeting them to damaged tissue also offers unique possibilities for augmenting a variety of other tissue repair mechanisms, the authors note. They also suggest that in some situations systemic administration of HMGB1 to achieve serum levels similar to those observed in their mouse model could be used as a therapeutic strategy to accelerate tissue regeneration.
“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 revolutionize the management of wound healing,” Dr. McGrath claims. “Our plan is to see if we can now use this scientific."