Tang Qiuling, Chen Qiurong, Lai Xiulan, Liu Sizheng, Chen Yezeng, Zheng Zexin, Xie Qingdong, Maldonado Martin, Cai Zhiwei, Qin Shan, Ho Guyu, Ma Lian
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.
PLoS One. 2013 Dec 10;8(12):e81844. doi: 10.1371/journal.pone.0081844. eCollection 2013.
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.
人脐带间充质干细胞(HUMSCs)具有高度增殖能力,可被诱导分化为所有三个胚层的高级衍生物。因此,HUMSCs被认为是细胞靶向治疗和组织工程的一个有前景的细胞来源。然而,有关于源自人骨髓的间充质干细胞(MSCs)自发转化的报道。目前尚不清楚HUMSCs是否具有自发恶性转化或经化学致癌物诱导恶性转化的能力。因此,我们从10名供体中分离出HUMSCs,并评估它们自发或用DNA损伤致癌物3-甲基胆蒽(3-MCA)处理后的转化潜能。通过形态变化、增殖率(增殖速率)、进入细胞衰老的能力、端粒酶活性、染色体异常以及体内形成肿瘤的能力来评估HUMSCs在体外的恶性转化。我们的研究表明,来自所有10名供体的HUMSCs最终进入衰老状态,未发生自发恶性转化。然而,用3-MCA处理的10名供体中的两名供体的HUMSCs显示增殖率增加,未能进入衰老状态,并表现出细胞形态改变。当将这些细胞(tHUMSCs)注射到免疫缺陷小鼠体内时,它们形成了肉瘤样或低分化肿瘤。此外,与HUMSCs相比,tHUMSCs在体外长期培养期间显示人端粒酶逆转录酶(hTERT)阳性表达,并且相对端粒长度未缩短。我们的研究表明,HUMSCs不易发生自发恶性转化。然而,化学致癌物3-MCA可诱导其发生恶性转化。