Tan Kenneth K B, Salgado Giorgiana, Connolly John E, Chan Jerry K Y, Lane E Birgitte
A(∗)STAR Institute of Medical Biology, Immunos, Singapore 138648, Singapore; NUS Graduate School for Integrative Sciences and Engineering, Centre for Life Sciences, Singapore 117597, Singapore.
A(∗)STAR Institute of Medical Biology, Immunos, Singapore 138648, Singapore.
Stem Cell Reports. 2014 Aug 12;3(2):324-38. doi: 10.1016/j.stemcr.2014.06.005. Epub 2014 Jul 10.
Epidermal stem cells have been in clinical application as a source of culture-generated grafts. Although applications for such cells are increasing due to aging populations and the greater incidence of diabetes, current keratinocyte grafting technology is limited by immunological barriers and the time needed for culture amplification. We studied the feasibility of using human fetal skin cells for allogeneic transplantation and showed that fetal keratinocytes have faster expansion times, longer telomeres, lower immunogenicity indicators, and greater clonogenicity with more stem cell indicators than adult keratinocytes. The fetal cells did not induce proliferation of T cells in coculture and were able to suppress the proliferation of stimulated T cells. Nevertheless, fetal keratinocytes could stratify normally in vitro. Experimental transplantation of fetal keratinocytes in vivo seeded on an engineered plasma scaffold yielded a well-stratified epidermal architecture and showed stable skin regeneration. These results support the possibility of using fetal skin cells for cell-based therapeutic grafting.
表皮干细胞已作为培养生成移植物的来源应用于临床。尽管由于人口老龄化和糖尿病发病率上升,此类细胞的应用正在增加,但目前的角质形成细胞移植技术受到免疫屏障和培养扩增所需时间的限制。我们研究了使用人胎儿皮肤细胞进行同种异体移植的可行性,结果表明,与成人角质形成细胞相比,胎儿角质形成细胞具有更快的扩增时间、更长的端粒、更低的免疫原性指标,并且具有更多干细胞指标的更高克隆形成能力。胎儿细胞在共培养中不会诱导T细胞增殖,并且能够抑制受刺激T细胞的增殖。然而,胎儿角质形成细胞在体外能够正常分层。将胎儿角质形成细胞接种在工程化血浆支架上进行体内实验性移植,产生了分层良好的表皮结构,并显示出稳定的皮肤再生。这些结果支持了使用胎儿皮肤细胞进行基于细胞的治疗性移植的可能性。