Characterization and modulation of human mesenchymal stem cell stress pathway response following hypothermic storage.
Characterization and modulation of human mesenchymal stem cell stress pathway response following hypothermic storage.
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DOI：
10.1016/j.cryobiol.2014.01.014
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发表时间：
2014-04
期刊：
影响因子：
2.7
通讯作者：
Van Buskirk, Robert G.
中科院分区：
文献类型：
--
作者：
Corwin, William L.;Baust, John M.;Baust, John G.;Van Buskirk, Robert G.
关键词：
人类间充质干细胞（hMSC）的研究在过去十年中呈指数增长。处理和保存这些细胞的能力对于它们在干细胞治疗中的应用至关重要。因此，理解与生物保存相关的复杂的、基于分子的应激反应对于改善结果和维持hMSC特有的干细胞特性是必要的。在该研究中，将hMSC在三种不同的培养基中暴露于冷藏（4°C）不同的时间间隔。研究了白藜芦醇或salubrinal的添加，以确定是否可以提高细胞对寒冷的耐受性。在样品中观察到储存后1小时细胞凋亡的快速升高以及在24小时恢复期内坏死水平的增加。白藜芦醇的添加导致hMSC存活的显著改善，而salubrinal的添加揭示了基于所利用的培养基的差异反应。在调节后观察到细胞凋亡和坏死的减少以及细胞应激/死亡信号蛋白水平的降低。此外，ER应激和随后的未折叠蛋白反应（UPR）应激途径激活涉及对hMSC低温储存的响应。这项研究是了解hMSC对冷暴露的应激反应的重要的第一步，并证明了特定应激途径的靶向分子调节对冷耐受性的影响，从而改善了结果。继续研究是必要的，以进一步阐明参与低温诱导的hMSC细胞死亡的分子机制。这项研究已经证明了通过靶向选择细胞应激途径来改善hMSC加工和储存的潜力。
Human mesenchymal stem cell (hMSC) research has grown exponentially in the last decade. The ability to process and preserve these cells is vital to their use in stem cell therapy. As such, understanding the complex, molecular-based stress responses associated with biopreservation is necessary to improve outcomes and maintain the unique stem cell properties specific to hMSC. In this study hMSC were exposed to cold storage (4°C) for varying intervals in three different media. The addition of resveratrol or salubrinal was studied to determine if either could improve cell tolerance to cold. A rapid elevation in apoptosis at 1 hour post-storage as well as increased levels of necrosis through the 24 hours of recovery was noted in samples. The addition of resveratrol resulted in significant improvements to hMSC survival while the addition of salubrinal revealed a differential response based on the media utilized. Decreases in both apoptosis and necrosis together with decreased cell stress/death signaling protein levels were observed following modulation. Further, ER stress and subsequent Unfolded Protein Response (UPR) stress pathway activation was implicated in response to hMSC hypothermic storage. This study is an important first step in understanding hMSC stress responses to cold exposure and demonstrates the impact of targeted molecular modulation of specific stress pathways on cold tolerance thereby yielding improved outcomes. Continued research is necessary to further elucidate the molecular mechanisms involved in hypothermic-induced hMSC cell death. This study has demonstrated the potential for improving hMSC processing and storage through targeting select cell stress pathways.
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影响因子：
1.6
作者：
Corwin, William L.;Baust, John M.;Van Buskirk, Robert G.
通讯作者：
Van Buskirk, Robert G.
影响因子：
5.6
作者：
Huang, Tsung-Teng;Lin, Hung-Chi;Lai, Hsin-Chih
通讯作者：
Lai, Hsin-Chih
DOI：
10.1097/meg.0b013e3283378405
发表时间：
2010-09-01
影响因子：
2.1
作者：
Al-Rawashdeh, Feras Y.;Scriven, Peter;Wyld, Lynda
通讯作者：
Wyld, Lynda
影响因子：
2.8
作者：
Clarke, Dominic M.;Robilotto, Anthony T.;Baust, John M.
通讯作者：
Baust, John M.
影响因子：
6.1
作者：
Biancone, Luigi;Bruno, Stefania;Camussi, Giovanni
通讯作者：
Camussi, Giovanni