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

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.