Division of Plastic Surgery, Department of Surgery, School of Medicine, Stanford University, Stanford, California.
APstem Therapeutics, Inc., Fremont, California.
Adv Wound Care (New Rochelle). 2020 May 1;9(5):264-276. doi: 10.1089/wound.2019.0974. Epub 2020 Mar 19.
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. We isolated and 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. 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. Nondermal-derived CD34 cells (BDPCs) from the adult unmobilized peripheral blood are capable of expansion and differentiation.Successful establishment of an technical platform for BDPCs expansion and differentiation.The expanded and differentiated epithelial-like cells (eBDPCs) enhance wound healing and directly contribute to skin regeneration and HFN. BDPCs isolated and expanded from adult peripheral blood may provide a possible new cell-based treatment strategy for HF neogenesis and skin wound regeneration.
位于毛囊(HF)隆起区域的表皮 CD34 干细胞能够诱导 HF 新生,并在移植后增强伤口愈合。在这项研究中,我们观察到来自血液的 CD34 细胞直接参与全层切除性伤口愈合过程中的真皮再生。我们从成年小鼠的外周血中分离和扩增了一组具有以下表面标志物的造血干细胞(HSC)样前体细胞:CD34、富含亮氨酸重复的 G 蛋白偶联受体 5(LGR5)、CD44、c-kit、谱系阴性(lin)和 E-钙粘蛋白。这些血液衍生的前体细胞(BDPCs)可以进一步分化为上皮样细胞(eBDPCs)并分泌成纤维细胞生长因子 9(Fgf9)蛋白。当将 eBDPC 移植到全层皮肤伤口中时,eBDPC 处理可加速愈合并增强皮肤结构再生,减少真皮瘢痕形成。此外,还观察到 HF 新生(HFN),标记的 BDPC 整合到伤口区域。来自成年未动员外周血的非真皮源性 CD34 细胞(BDPCs)能够扩增和分化。成功建立了 BDPCs 扩增和分化的技术平台。扩增和分化的上皮样细胞(eBDPCs)增强了伤口愈合,并直接促进了皮肤再生和 HFN。从成年外周血中分离和扩增的 BDPC 可能为 HF 新生和皮肤伤口再生提供一种新的基于细胞的治疗策略。