Department of Obstetrics and Gynaecology, National University of Singapore, Singapore, Singapore.
Reprod Biomed Online. 2012 Feb;24(2):235-46. doi: 10.1016/j.rbmo.2011.10.007. Epub 2011 Oct 22.
Tumorigenesis is the major obstacle of tissues derived from human embryonic stem cells (ESC) and human induced pluripotent stem cell (IPSC) for transplantation therapy. This prompted a search for other sources of ESC. This study isolated and characterized stem cells from the extra-embryonic human umbilical cord Wharton's jelly (WJSC). These cells are non-controversial, available in abundance, proliferative, multipotent and hypoimmunogenic. However, their tumorigenic potential has not been properly addressed. Their tumour-producing capabilities were compared with human ESC using the immunodeficient mouse model. Unlabelled human ESC+matrigel (2×10(6)cells/site), labelled human WJSC (red fluorescent protein; 5×10(6)cells/site) and unlabelled human WJSC+matrigel (5×10(6)cells/site) were injected via three routes (s.c., i.m. and i.p.). Animals that received human ESC+matrigel developed teratomas in 6 weeks (s.c. 85%; i.m. 75%; i.p. 100%) that contained tissues of ectoderm, mesoderm and endoderm. No animal that received human WJSC developed tumours or inflammatory reactions at the injection sites when maintained for a prolonged period (20 weeks). Human WJSC produced increases in anti-inflammatory cytokines in contrast to human ESC, which increased pro-inflammatory cytokines. Human WJSC, being hypoimmunogenic and non-tumorigenic, have the potential for safe cell-based therapies.
肿瘤发生是将人类胚胎干细胞(ESC)和人类诱导多能干细胞(iPSC)衍生的组织用于移植治疗的主要障碍。这促使人们寻找其他 ESC 来源。本研究从人类脐带 Wharton 胶(WJSC)中分离和鉴定了干细胞。这些细胞无争议、丰富、增殖、多能且低免疫原性。然而,它们的致瘤潜力尚未得到妥善解决。使用免疫缺陷小鼠模型比较了它们的肿瘤生成能力与人类 ESC。未标记的人类 ESC+matrigel(2×10(6)个细胞/部位)、标记的人类 WJSC(红色荧光蛋白;5×10(6)个细胞/部位)和未标记的人类 WJSC+matrigel(5×10(6)个细胞/部位)通过三种途径(s.c.,i.m. 和 i.p.)注射。接受人类 ESC+matrigel 的动物在 6 周内(s.c. 85%;i.m. 75%;i.p. 100%)形成了包含外胚层、中胚层和内胚层组织的畸胎瘤。当维持较长时间(20 周)时,接受人类 WJSC 的动物在注射部位未发生肿瘤或炎症反应。与人类 ESC 相比,人类 WJSC 产生了增加抗炎细胞因子,而人类 ESC 增加了促炎细胞因子。人类 WJSC 具有低免疫原性和非致瘤性,有用于安全细胞治疗的潜力。