Treatment of Full-Thickness Skin Wounds with Blood-Derived CD34+ Precursor Cells Enhances Healing with Hair Follicle Regeneration

Objective: Epidermal CD34(+) stem cells located in the hair follicle (HF) bulge area are capable of inducing HF neogenesis and enhancing wound healing after transplantation. In this study, we observed CD34(+) cells derived from blood directly participate in dermal regeneration during full-thickness excisional wound healing. Approach: We isolated and in vitro expanded a subset of hematopoietic stem cell (HSC)-like precursor cells from the peripheral blood of adult mice with the surface markers: CD34(+), leucine rich repeat containing G protein-coupled receptor 5 (LGR5)(+), CD44(+), c-kit(+), lineage negative (lin(−)), and E-cadherin(−). These blood-derived precursor cells (BDPCs), can be further differentiated into epithelial-like cells (eBDPCs) and secret fibroblast growth factor 9 (Fgf9) protein. Result: When transplanted into full-thickness skin wounds, eBDPC treatment produced accelerated healing and enhanced skin structure regeneration with less dermal scar formation. Also, HF neogenesis (HFN) was observed with incorporation of labeled BDPCs in the wound area. Innovation: Nondermal-derived CD34(+) cells (BDPCs) from the adult unmobilized peripheral blood are capable of in vitro expansion and differentiation. Successful establishment of an in vitro technical platform for BDPCs expansion and differentiation. The in vitro expanded and differentiated epithelial-like cells (eBDPCs) enhance wound healing and directly contribute to skin regeneration and HFN. Conclusion: BDPCs isolated and expanded from adult peripheral blood may provide a possible new cell-based treatment strategy for HF neogenesis and skin wound regeneration.