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放射抗性间充质干细胞:抗性机制及其临床潜在意义

Radio-resistant mesenchymal stem cells: mechanisms of resistance and potential implications for the clinic.

作者信息

Nicolay Nils H, Lopez Perez Ramon, Saffrich Rainer, Huber Peter E

机构信息

Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany.

Heidelberg Institute for Radiation Oncology (HIRO), National Center for Radiation Research in Oncology, Heidelberg, Germany.

出版信息

Oncotarget. 2015 Aug 14;6(23):19366-80. doi: 10.18632/oncotarget.4358.

Abstract

Mesenchymal stem cells (MSCs) comprise a heterogeneous population of multipotent stromal cells and can be isolated from various tissues and organs. Due to their regenerative potential, they have been subject to intense research efforts, and they may provide an efficient means for treating radiation-induced tissue damage. MSCs are relatively resistant to ionizing radiation and retain their stem cell characteristics even after high radiation doses. The underlying mechanisms for the observed MSC radioresistance have been extensively studied and may involve efficient DNA damage recognition, double strand break repair and evasion of apoptosis. Here, we present a concise review of the published scientific data on the radiobiological features of MSCs. The involvement of different DNA damage recognition and repair pathways in the creation of a radioresistant MSC phenotype is outlined, and the roles of apoptosis, senescence and autophagy regarding the reported radioresistance are summarized. Finally, potential influences of the radioresistant MSCs for the clinic are discussed with respect to the repair and radioprotection of irradiated tissues.

摘要

间充质干细胞(MSCs)由多能基质细胞的异质群体组成,可从各种组织和器官中分离出来。由于其再生潜力,它们一直是深入研究的对象,并且可能为治疗辐射诱导的组织损伤提供一种有效的手段。间充质干细胞对电离辐射具有相对抗性,即使在高辐射剂量后仍能保持其干细胞特征。关于观察到的间充质干细胞放射抗性的潜在机制已得到广泛研究,可能涉及有效的DNA损伤识别、双链断裂修复和凋亡逃避。在此,我们简要综述已发表的关于间充质干细胞放射生物学特征的科学数据。概述了不同DNA损伤识别和修复途径在产生放射抗性间充质干细胞表型中的作用,并总结了凋亡、衰老和自噬在报道的放射抗性中的作用。最后,就辐射组织的修复和放射防护方面,讨论了放射抗性间充质干细胞对临床的潜在影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46d4/4637291/cdb00086b651/oncotarget-06-19366-g001.jpg

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