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胚胎外人类沃顿氏胶干细胞不像人类胚胎干细胞那样会引起肿瘤生成。

Extra-embryonic human Wharton's jelly stem cells do not induce tumorigenesis, unlike human embryonic stem cells.

机构信息

Department of Obstetrics and Gynaecology, National University of Singapore, Singapore, Singapore.

出版信息

Reprod Biomed Online. 2012 Feb;24(2):235-46. doi: 10.1016/j.rbmo.2011.10.007. Epub 2011 Oct 22.

Abstract

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.

摘要

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。

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