Cátedra de Citología, Histología y Embriología, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Buenos Aires CP 1900, Argentina.
Instituto de Neurociencias (INEU), Fundación para la Lucha contra Enfermedades Neurológicas de la Infancia-Consejo Nacional de Investigaciones Científicas y Técnicas (FLENI-CONICET) Escobar, Buenos Aires CP B1625, Argentina.
Int J Mol Sci. 2024 Feb 16;25(4):2350. doi: 10.3390/ijms25042350.
Wound healing after skin injury is a complex process, particularly in equines where leg wounds are prevalent and their repair is complicated due to the anatomical characteristics. Conventional treatments are not effective enough. The umbilical cord offers an unlimited source of adult mesenchymal stem cells (ucMSCs) from Wharton's jelly tissue. The present study aims to demonstrate the safety and therapeutic potential of the allogeneic use of equine ucMSCs (e-ucMSCs) in the healing of severe equine leg wounds. The methods employed were the isolation, culture and expansion of e-ucMSCs. Flow cytometry and a PCR assay were used for cell characterization. This study included an immunomodulation assay, a murine pre-clinical trial and the first phase of an equine clinical trial. Our results showed that e-ucMSCs express a functional HLA-G homolog, EQMHCB2. In the immunomodulation assay, the e-ucMSCs inhibited the proliferation of activated equine peripheral blood mononuclear cells (e-PBMCs). In the murine pre-clinical trial, e-ucMSCs reduced healing time by 50%. In the equine clinical trial, the injection of e-ucMSCs into severe leg lesions improved the closure time and quality of the tissues involved, regenerating them without fibrous tissue scar formation. In conclusion, the results of this study suggest that e-ucMSCs can be used allogeneically for wound healing by creating a tolerogenic environment.
皮肤损伤后的伤口愈合是一个复杂的过程,特别是在腿部伤口普遍存在且由于解剖学特征导致其修复复杂的马中。传统的治疗方法效果不够理想。脐带为 Wharton 胶组织中的成体间充质干细胞(ucMSCs)提供了无限的来源。本研究旨在证明同种异体使用马脐带间充质干细胞(e-ucMSCs)治疗严重马腿部伤口的安全性和治疗潜力。采用的方法是 e-ucMSCs 的分离、培养和扩增。流式细胞术和 PCR 检测用于细胞特征鉴定。本研究包括免疫调节检测、小鼠临床前试验和马临床 I 期试验。我们的结果表明,e-ucMSCs 表达功能性 HLA-G 同源物 EQMHCB2。在免疫调节检测中,e-ucMSCs 抑制了激活的马外周血单核细胞(e-PBMCs)的增殖。在小鼠临床前试验中,e-ucMSCs 将愈合时间缩短了 50%。在马临床 I 期试验中,将 e-ucMSCs 注射到严重的腿部病变中,改善了组织的闭合时间和质量,使其再生而无纤维组织瘢痕形成。总之,本研究结果表明,e-ucMSCs 可以通过创造耐受环境用于异体伤口愈合。