title: Malignant transformation potentials of human umbilical cord mesenchymal stem cells both spontaneously and via 3-methycholanthrene induction.
abstract: Human umbilical cord mesenchymal stem cells (HUMSCs) are highly proliferative and can be induced to differentiate into advanced derivatives of all three germ layers. Thus, HUMSCs are considered to be a promising source for cell-targeted therapies and tissue engineering. However there are reports on spontaneous transformation of mesenchymal stem cells (MSCs) derived from human bone marrows. The capacity for HUMSCs to undergo malignant transform spontaneously or via induction by chemical carcinogens is presently unknown. Therefore, we isolated HUMSCs from 10 donors and assessed their transformation potential either spontaneously or by treating them with 3-methycholanthrene (3-MCA), a DNA-damaging carcinogen. The malignant transformation of HUMSCs in vitro was evaluated by morphological changes, proliferation rates, ability to enter cell senescence, the telomerase activity, chromosomal abnormality, and the ability to form tumors in vivo. Our studies showed that HUMSCs from all 10 donors ultimately entered senescence and did not undergo spontaneous malignant transformation. However, HUMSCs from two of the 10 donors treated with 3-MCA displayed an increased proliferation rate, failed to enter senescence, and exhibited an altered cell morphology. When these cells (tHUMSCs) were injected into immunodeficient mice, they gave rise to sarcoma-like or poorly differentiated tumors. Moreover, in contrast to HUMSCs, tHUMSCs showed a positive expression of human telomerase reverse transcriptase (hTERT) and did not exhibit a shortening of the relative telomere length during the long-term culture in vitro. Our studies demonstrate that HUMSCs are not susceptible to spontaneous malignant transformation. However, the malignant transformation could be induced by chemical carcinogen 3-MCA.
authors: Transforming Medical Center, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China ; Department of Pediatrics, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors: Qiuling
authors: Q
authors: Tang
authors: Qiurong
authors: Q
authors: Chen
authors: Xiulan
authors: X
authors: Lai
authors: Sizheng
authors: S
authors: Liu
authors: Yezeng
authors: Y
authors: Chen
authors: Zexin
authors: Z
authors: Zheng
authors: Qingdong
authors: Q
authors: Xie
authors: Martin
authors: M
authors: Maldonado
authors: Zhiwei
authors: Z
authors: Cai
authors: Shan
authors: S
authors: Qin
authors: Guyu
authors: G
authors: Ho
authors: Lian
authors: L
authors: Ma
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016922:Cellular Senescence / Q000187:drug effects; D002869:Chromosome Aberrations / Q000139:chemically induced*; D004249:DNA Damage; D005312:Fetal Blood / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D002273:Carcinogens