Nanofiber-expanded human umbilical cord blood-derived CD34+ cell therapy accelerates cutaneous wound closure in NOD/ SCID mice.

Nanofiber-expanded human umbilical cord blood-derived CD34⁺ cell therapy has been shown to have potential applications for peripheral and myocardial ischaemic diseases. However, the efficacies of expanded CD34⁺ cell therapy for treating cutaneous wounds and its mechanisms of action have yet to be established. Using an excisional wound model in non-obese diabetic/severe combined immune deficient mice, we show herein that CD34⁺ cells accelerate the wound-healing process by enhancing collagen synthesis, and increasing fibroblast cell migration within the wound bed. Concomitantly, reduced levels of matrix metalloproteinase ( MMPs) such as MMP1, MMP3, MMP9 and MMP13 were detected in the wound beds of animals treated with CD34⁺ cells compared with vehicle-treated controls. CD34⁺ cells were found to mediate enhanced migration and proliferation of dermal fibroblast cells in vitro. Moreover, CD34⁺ cells secrete collagen in a serum-deprived environment. In mechanistic studies, co-culture of CD34⁺ cells with primary skin fibroblasts increased the expression of collagen1A1, a component of type 1 collagen, and decreased the expression of MMP1 in fibroblast cells in the presence of a proteasome inhibitor. Finally, CD34⁺ cell-mediated functions were transcriptionally regulated by the c-Jun N-terminal kinases pathway. Collectively, these data provide evidence of therapeutic efficacy and a novel mechanism of nanofiber-expanded CD34⁺ cell-mediated accelerated wound healing. [ABSTRACT FROM AUTHOR]