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与干细胞和癌症干细胞冷冻保存及储存相关的关键问题:保护生物完整性。

Key Issues Related to Cryopreservation and Storage of Stem Cells and Cancer Stem Cells: Protecting Biological Integrity.

作者信息

Karimi-Busheri Feridoun, Rasouli-Nia Aghdass, Weinfeld Michael

机构信息

Department of Oncology, University of Alberta, Edmonton, AB, Canada.

Department of Oncology, Cross Cancer Institute and University of Alberta, Edmonton, AB, Canada.

出版信息

Adv Exp Med Biol. 2016;951:1-12. doi: 10.1007/978-3-319-45457-3_1.

DOI:10.1007/978-3-319-45457-3_1
PMID:27837550
Abstract

Cryopreservation and biobanking of stem cells are becoming increasingly important as stem cell technology and application attract the interest of industry, academic research, healthcare and patient organisations. Stem cell are already being used in the treatment of some diseases and it is anticipated that stem cell therapy will play a central role in future medicine. Similarly, the discovery of both hematopoietic and solid tumor stem cells and their clinical relevance have profoundly altered paradigms for cancer research as the cancer stem cells are considered promising new targets against cancer. Consequently, long-term cryopreservation and banking of normal and malignant stem cells is crucial and will inevitably become a routine procedure that requires highly regulated and safe methods of specimen storage. There is, however, an increasing amount of evidence showing contradictory results on the impact of cryopreservation and thawing of stem cells, including extensive physical and biological stresses, apoptosis and necrosis, mitochondrial injuries, changes to basal respiration and ATP production, cellular structural damage, telomere shortening and cellular senescence, and DNA damage and oxidative stress. Notably, cell surface proteins that play a major role in stem cell fate and are used as the biomarkers of stem cells are more vulnerable to cold stress than other proteins. There are also data supporting the alteration in some biological features and genetic integrity at the molecular level of the post-thawed stem cells. This article reviews the current and future challenges of cryopreservation of stem cells and stresses the need for further rigorous research on the methodologies for freezing and utilizing cancer stem cells following long-term storage.

摘要

随着干细胞技术与应用吸引了产业界、学术研究、医疗保健及患者组织的关注,干细胞的冷冻保存和生物样本库建设正变得愈发重要。干细胞已被用于某些疾病的治疗,并且预计干细胞疗法将在未来医学中发挥核心作用。同样,造血干细胞和实体瘤干细胞的发现及其临床意义深刻改变了癌症研究的范式,因为癌症干细胞被视为对抗癌症的有前景的新靶点。因此,正常和恶性干细胞的长期冷冻保存和样本库建设至关重要,并且将不可避免地成为一项需要高度规范且安全的样本储存方法的常规程序。然而,越来越多的证据表明,干细胞冷冻保存和解冻的影响存在矛盾结果,包括广泛的物理和生物应激、凋亡和坏死、线粒体损伤、基础呼吸和ATP产生的变化、细胞结构损伤、端粒缩短和细胞衰老,以及DNA损伤和氧化应激。值得注意的是,在干细胞命运中起主要作用并用作干细胞生物标志物的细胞表面蛋白比其他蛋白更容易受到冷应激的影响。也有数据支持解冻后干细胞在分子水平上某些生物学特征和遗传完整性的改变。本文综述了干细胞冷冻保存的当前及未来挑战,并强调需要对长期储存后冷冻和利用癌症干细胞的方法进行进一步严格研究。

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