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间充质干细胞、癌症挑战与新方向。

Mesenchymal stem cells, cancer challenges and new directions.

机构信息

Near East University, Medical Faculty, Lefkosa, Mersin 10, Turkey.

Near East University, Medical Faculty, Lefkosa, Mersin 10, Turkey.

出版信息

Eur J Cancer. 2014 May;50(8):1522-30. doi: 10.1016/j.ejca.2014.02.011. Epub 2014 Mar 7.

DOI:10.1016/j.ejca.2014.02.011
PMID:24613620
Abstract

Therapeutic use of multipotent mesenchymal stromal stem cells (MSC) is a promising venue for a large number of degenerative diseases and cancer. Their availability from many different adult tissues, ease of expansion in culture, the ability to avoid immune rejection and their homing ability, are some of the properties of MSCs that make them a great resource for therapy. However, the challenges and risks for cell-based therapies are multifaceted. The blessing of cell culture expansion also comes with a burden. During in vitro expansion, stem cells experience a long replicative history and therefore, become subjected to damage from intracellular and extracellular influences. As previously shown cells that are manipulated to obtain an expanded replicative potential are prone to spontaneous transformation in culture. These manipulations help bypass the naturally built-in controls of the cell that govern the delicate balance between cell proliferation, senescence and carcinogenesis. Because of this, there is a risk for patients receiving stem cells that are in vitro expanded. Whether these cells are genetically engineered or harbouring xenogenic compounds, they cannot truly be considered "safe" unless the cells are closely monitored. In the present communication, we will focus on the therapeutic potential of the human mesenchymal stem cells (hMSC) with special focus on their use in cancer therapy. We will consider different mechanisms, by which stem cells can maintain telomeres and thereby the cell's ability to be expanded in vitro, and also focus on a new therapeutic venue that utilises hMSCs as delivery vehicles in innovative new cancer treatments.

摘要

多能间充质基质细胞(MSC)的治疗用途是许多退行性疾病和癌症的有前途的治疗方法。它们可以从许多不同的成人组织中获得,在培养中易于扩增,具有避免免疫排斥的能力和归巢能力,这些都是 MSC 使其成为治疗的重要资源的特性。然而,细胞疗法的挑战和风险是多方面的。细胞培养扩增的好处也带来了负担。在体外扩增过程中,干细胞经历了漫长的复制历史,因此容易受到细胞内和细胞外影响的损伤。如前所述,为了获得扩增的复制潜力而进行操作的细胞在培养中容易自发转化。这些操作有助于绕过细胞中内置的自然控制,这些控制调节细胞增殖、衰老和癌变之间的微妙平衡。因此,接受体外扩增的干细胞的患者存在风险。除非对这些细胞进行密切监测,否则这些细胞无论是经过基因工程改造还是含有异种化合物,都不能真正被认为是“安全的”。在本通讯中,我们将重点介绍人类间充质干细胞(hMSC)的治疗潜力,特别关注它们在癌症治疗中的应用。我们将考虑干细胞可以维持端粒的不同机制,从而使细胞能够在体外扩增,并且还将关注一种新的治疗途径,即利用 hMSC 作为创新癌症治疗的输送载体。

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