Momin Eric N, Vela Guillermo, Zaidi Hasan A, Quiñones-Hinojosa Alfredo
Department of Neurosurgery and Oncology, The Johns Hopkins School of Medicine, Baltimore, MD.
Curr Immunol Rev. 2010 May 1;6(2):137-148. doi: 10.2174/157339510791111718.
Mesenchymal stem cells (MSCs) represent a promising new approach to the treatment of several diseases that are associated with dismal outcomes. These include myocardial damage, graft versus host disease, and possibly cancer. Although the potential therapeutic aspects of MSCs continue to be well-researched, the possible hazards of MSCs, and in particular their oncogenic capacity are poorly understood. This review addresses the oncogenic and tumor-supporting potential of MSCs within the context of cancer treatment. The risk for malignant transformation is discussed for each stage of the clinical lifecycle of MSCs. This includes malignant transformation in vitro during production phases, during insertion of potentially therapeutic transgenes, and finally in vivo via interactions with tumor stroma. The immunosuppressive qualities of MSCs, which may facilitate evasion of the immune system by a tumor, are also addressed. Limitations of the methods employed in clinical trials to date are reviewed, including the absence of long term follow-up and lack of adequate screening methods to detect formation of new tumors. Through discussions of the possible oncogenic and tumor-supporting mechanisms of MSCs, directions for future research are identified which may eventually facilitate the future clinical translation of MSCs for the treatment of cancer and other diseases.
间充质干细胞(MSCs)是治疗多种预后不佳疾病的一种有前景的新方法。这些疾病包括心肌损伤、移植物抗宿主病,可能还包括癌症。尽管MSCs的潜在治疗作用仍在深入研究,但人们对MSCs可能存在的危害,尤其是其致癌能力了解甚少。本综述探讨了在癌症治疗背景下MSCs的致癌和肿瘤支持潜力。讨论了MSCs临床生命周期各阶段发生恶性转化的风险。这包括在生产阶段体外培养过程中、插入潜在治疗性转基因过程中以及最终通过与肿瘤基质相互作用在体内发生的恶性转化。还讨论了MSCs的免疫抑制特性,其可能会促使肿瘤逃避免疫系统。回顾了迄今为止临床试验中所采用方法的局限性,包括缺乏长期随访以及缺乏检测新肿瘤形成的充分筛查方法。通过讨论MSCs可能的致癌和肿瘤支持机制,确定了未来的研究方向,这最终可能会促进MSCs在癌症及其他疾病治疗中的临床转化。