Side population hematopoietic stem cells promote wound healing in diabetic mice

Background: Early evidence suggests that stem cells play a role in normal wound healing. Various impaired wound-healing states might be due to a deficiency in the stem cell repertoire. The authors sought to demonstrate that a new subset of lymphoid progenitor murine hematopoietic stem cells will accelerate wound healing in diabetic mice. Methods: Bone marrow cells were harvested from C57B16/J femurs and separated into side and main populations based on their ability to efflux the vital dye Hoechst 33342 and the presence or absence of CD7 and CD34 markers. Side or main population cells and control solution were applied once topically to 1-cm(2) full-thickness dorsal excisional wounds in lepr db/db and wild-type mice on the day after wounding (n = 12 in each group). Wound closure was followed by computer planimetry. Wounds were harvested after 7 and 25 days for histological analysis. Results: Topical side population treatment had a significant effect on wound closure in diabetic animals, with a higher percentage of wound closure (35 +/- 7.2 percent) in this group on postoperative day 7 compared with animals treated with either main population cells (16 +/- 4.9 percent) or a vehicle control using saline (14 +/- 6.7 percent) (p < 0.05). When side population cells were given to wild-type mice that already had a normal stem cell repertoire, there was a trend toward better wound closure, but no significant differences were found. Conclusions: Side population-treated wounds healed more quickly than main population-or control-treated wounds in diabetic mice, suggesting that one stem cell subpopulation, but not the majority, harbors the potential for improving the healing process. Further studies are needed to investigate the mechanism of healing and to explore its potential as a therapeutic agent.