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 × 106 cells/site), labelled human WJSC (red fluorescent protein; 5 × 106 cells/site) and unlabelled human WJSC + matrigel (5 × 106 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.Human embryonic stem cells (human ESC) and human induced pluripotent stem cells (IPSC) are versatile as they can be converted to all the tissue types of the human body (pluripotency). However, a major clinical hurdle in using hESC- and IPSC-derived tissues for treating disease is their ability to produce tumours. This disadvantage prompted our search for a novel stem cell in the human Wharton’s jelly, a gelatinous substance in the umbilical cord. Human Wharton’s jelly stem cells (WJSC) are available in large numbers, can be grown easily in culture, have prolonged stem cell-like properties, can be converted into many desirable tissues and, when transplanted into diseased animal models, correct disease. However, since their ability to produce tumours has not been properly addressed, we compared their tumour-forming capabilities with human ESC in immunodeficient mice. Human ESC (2 × 106 cells/site) and human WJSC (5 × 106 cells/site) were injected via three routes: under the skin (subcutaneous), into muscle (intramuscular) and into the abdominal cavity (intraperitoneal). All animals that received human ESC developed tumours in 6 weeks and there were no tumours in the animals receiving human WJSC, even when monitored for 20 weeks. Also, the animals receiving human ESC showed immunological responses while those receiving human WJSC did not. We conclude that human WJSC have enormous potential for cell-based therapies as they do not induce tumours and are not rejected when transplanted.