Person:

Chen, Bing

Previous experimental studies to assess the contribution of blood-borne circulating (BBC) cells to cutaneous wound healing have relied on discontinuous pulsing of labeled BBC elements or bone marrow transplant protocols. Such approaches do not allow the examination of stable BBC cells that have matured in a physiologically normal host. We have used a parabiotic murine model for cutaneous wound healing to evaluate the relative contribution of stable populations of peripheral blood cells expressing the green fluorescent protein (GFP) transgene in otherwise normal animals. Circulating cells (mature and immature) expressing the GFP transgene were easily detected and quantified in wounds of GFP− parabiotic twins during all evaluated stages of the healing response. Using multiple antibody probes, the relative contribution of various subsets of BBC cells could be comparatively assessed. In early wounds, some cells expressing mesenchymal epitopes were documented to be of hematopoietic origin, indicating the utility of this model in assessing cell plasticity in the context of tissue regeneration and repair. Application of this approach enables further investigation into the contribution of peripheral blood in normal and abnormal healing responses.

Impaired repair of skin defects is a major complication of diabetes; yet, the pathophysiology of diabetic (db) wound healing remains largely opaque. Here, we investigate the role of humoral factors in modulating db wound repair by generating chimeric animals through parabiotic joining of wild-type (wt) and diabetic (db/db) mice. This strategy allows wounds on healing-deficient db/db mice to be exposed to factors derived from the wt circulation at physiologically appropriate concentrations. When compared with db controls, chimeric db/db animals showed significantly improved healing of full-thickness, cutaneous wounds, with enhanced granulation tissue formation, angiogenesis, cell proliferation, and collagen deposition. Glycemic control was unaffected by parabiosis; however, the distribution of circulating leukocytes, altered in db controls, normalized in db-chimeras. Both wt and db cells were recruited from circulation into db wounds, but wt cells never exceeded 20% of total cells. Improved angiogenesis persisted in db-chimeras separated 24 hours after wounding, suggesting the existence of long-term normalizing factors. This study establishes a new model for studying db wound healing, and shows a key role for circulating factors in normalizing wound repair in diabetes.