骨髓间充质干细胞应用的风险:促瘤及成瘤性

Risks in the application of bone marrow-derived mesenchymal stem cells: tumor enhancement and tumorigeness

骨髓间充质干细胞(BMSCs)应用的安全性已经越来越受到关注,BMSCs可通过以下机制促进肿瘤生长并形成肿瘤。首先作为一种免疫缺陷细胞,BMSCs可逃避T细胞的识别,并通过IDO,PEGE2等多种途径抑制T、B淋巴细胞增殖及功能。其次,BMSCs还可能分化为内皮细胞及血管周细胞,参与构建肿瘤基质而促肿瘤生长。再次,有研究显示,长期体外扩增BMSCs,可致其出现永生化并显现肿瘤细胞特点,如形态变小而致密,表面标志物表达异常,接触抑制减弱及端粒酶活性增强等,移植入动物体内,可形成肉瘤。BMSCs恶性转变及成瘤的遗传学原因与染色体不稳定或基因序列错误累积有关,包括染色体增加、缺失及转位等。本文就近期有关骨髓间充质干细胞应用安全性的研究进行综述。

More and more attention has been paid to the safety of bone marrow-derived stem cells （BMSCs） those may enhance the tumor growth and form tumors by the following mechanisms. Firstly, as a kind of immunodeficient cells, BMSCs have the ability of avoiding immunological recognition and suppressing the proliferation and functions of T and B lymphocytes cells through multiple pathways, such as IDO and PEGE2. Secondly, BMSCs promote tumor growth by participating in the establishment of stroma as endothelial and perivascular cells. Thirdly, Researches have revealed that long-term expansion in vitro caused immortalization and malignant changing of BMSCs, including cytomorphological changes,abnormal surface markers, loss of the contact inhibition and enhancing of the telomerase activities. After transplantation, those cells formed sarcomas in the animal models. The genetic reasons leading to the malignant transformation and tumorigeness of BMSCs may be the instability and accumulation of errors in DNA, including amplification, deletion and translocation. This review provides insights into the recent studies on the safety of BMSCs application.