Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J Burn Care Res. 2024 Jan 5;45(1):234-241. doi: 10.1093/jbcr/irad153.
Skin substitutes including allografts remain a standard therapeutic approach to promote healing of both acute and chronic large wounds. However, none have resulted in the regrowth of lost and damaged tissues and scarless wound healing. Here, we demonstrate skin allograft chimerism and repair through the mobilization of endogenous bone marrow-derived stem and immune cells in rats and swine. We show that pharmacological mobilization of bone marrow stem cells and immune cells into the circulation promotes host repopulation of skin allografts and restoration of the skin's normal architecture without scarring and minimal contracture. When skin allografts from DA rats are transplanted into GFP transgenic Lewis recipients with a combination of AMD3100 and low-dose FK506 (AF) therapy, host-derived GFP-positive cells repopulate and/or regenerate cellular components of skin grafts including epidermis and hair follicles and the grafts become donor-host chimeric skin. Using AF combination therapy, burn wounds with skin allografts were healed by newly regenerated chimeric skin with epidermal appendages and pigmentation and without contracture in swine.
皮肤替代物包括同种异体移植物仍然是促进急性和慢性大伤口愈合的标准治疗方法。然而，没有一种方法能导致失去和受损组织的再生以及无疤痕的伤口愈合。在这里，我们在大鼠和猪中证明了通过动员内源性骨髓来源的干细胞和免疫细胞实现皮肤同种异体移植物嵌合和修复。我们表明，骨髓干细胞和免疫细胞的药理学动员进入循环促进了皮肤同种异体移植物的宿主再定植，并恢复了皮肤的正常结构，没有疤痕和最小的挛缩。当用 AMD3100 和低剂量 FK506（AF）联合治疗将 GFP 转基因 Lewis 受体中的 DA 大鼠皮肤同种异体移植物移植时，宿主来源的 GFP 阳性细胞再定植和/或再生皮肤移植物的细胞成分，包括表皮和毛囊，移植物成为供体-宿主嵌合皮肤。使用 AF 联合治疗，猪的皮肤同种异体移植物烧伤创面通过新再生的具有表皮附属物和色素沉着的嵌合皮肤愈合，没有挛缩。
