Differentiation of equine induced pluripotent stem cells into a keratinocyte lineage

伤口愈合受损是人类和兽医患者的共同问题。在马身上，慢性无法愈合的伤口对福利造成了影响，并对马产业产生了重大的经济影响。慢性不愈合伤口的一个关键组成部分是缺乏上皮覆盖（表皮）。**基于成体干细胞移植的皮肤移植技术的进步代表了治疗慢性伤口的新方法。不幸的是，由此产生的皮肤替代品缺少毛囊和汗腺。另一方面，胚胎干细胞能够转化为许多不同的细胞类型，这可能会产生更完整的移植物。然而，伦理和技术问题阻碍了实现胚胎细胞的全部潜力。**最近发现，成人细胞可以被重新编程为胚胎样状态，这为组织修复和再生提供了巨大的潜力。事实上，这些诱导多能细胞可以转化为角质形成细胞，从而建立一个功能齐全的表皮，至少在小鼠中是这样。**本研究旨在开发一种方法，迫使马的诱导多能干细胞转化为功能齐全的皮肤角质形成细胞，并利用这些细胞在移植到马的伤口上时重建正常的表皮覆盖物。**在马伤口模型中取得的进展可能有助于在进入人类临床环境之前验证基于干细胞的治疗方法

Impaired wound healing is a common problem in both human and veterinary patients. In the horse, chronic non-healing wounds pose a welfare implication and bear a significant financial impact on the equine industry. A critical component of chronic non-healing wounds is the absence of an epithelial cover (epidermis).**Advances in skin grafting technology, based on the transplantation of adult stem cells, represent a novel approach to treating chronic wounds. Unfortunately, the resultant skin substitute lacks hair follicles and sweat glands. Embryonic stem cells, on the other hand, are able to commit to many different cell types, which may allow the generation of more complete grafts. However, ethical and technical problems preclude realizing the full potential of embryonic cells. **The recent discovery that adult cells can be reprogrammed to an embryonic-like state presents enormous potential for tissue repair and regeneration. Indeed, these induced pluripotent cells can transform into keratinocytes and thus establish a fully functional epidermis, at least in the mouse. **This study aims to develop a method to force induced pluripotent stem cells of horses to commit to a fully functional skin keratinocyte and to use these cells in an effort to reconstitute a normal epidermal cover when grafted onto wounds of horses. **Advances achieved in the horse wound model may aid the validation of stem cell-based therapies required prior to moving into the human clinical setting.**