Old bone marrow cells inhibit skin wound vascularization.

Local injection of hematopoietic stem cell-enriched cells, including mouse lin- cells, accelerates vascularization in animal injury models, apparently by release of angiogenic factors. Locally injected lin- cells from nondiabetic mice dramatically improve, but those from obese diabetic mice inhibit vascular growth in obese diabetic mouse skin wounds. Because of similarities between diabetes and aging and because autologous bone marrow-derived cells are currently being tested in clinical trials involving older patients, we investigated the effects of old lin- cells on skin wound vascularization in nondiabetic and obese diabetic mice. Treatment with old lin- bone marrow cells resulted in decreased vessel size and numerical density, leading to profoundly reduced vascular volume density in wounds of non-diabetic and diabetic mice. Our data suggest that bone marrow-derived cells may be poor candidates for therapeutic use in older patients and could actually harm them.