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Modulating the distribution and fate of exogenously delivered MSCs to enhance therapeutic potential: knowns and unknowns
Intensive Care Medicine Experimental Pub Date : 2019-07-01 , DOI: 10.1186/s40635-019-0235-4
Claire H Masterson 1, 2 , Gerard F Curley 3 , John G Laffey 1, 2, 4
Affiliation  

Mesenchymal stem/stromal cells (MSCs) are undergoing intensive translational research for several debilitating conditions, including critical illnesses such as ARDS and sepsis. MSCs exert diverse biologic effects via their interaction with host tissues, via mechanisms that require the MSC to be in close proximity to the area of injury. Fully harnessing the therapeutic potential of advanced medicinal therapeutic products such as MSCs and their successful translation to clinical use requires a detailed understanding of MSC distribution and persistence in the injured tissues. Key aspects include understanding MSC distribution within the body, the response of the host to MSC administration, and the ultimate fate of exogenously administered MSCs within the host. Factors affecting this interaction include the MSC tissue source, the in vitro MSC culture conditions, the route of MSC administration and the specific issues relating to the target disease state, each of which remains to be fully characterised. Understanding these factors may generate strategies to modify MSC distribution and fate that may enhance their therapeutic effect. This review will examine our understanding of the mechanisms of action of MSCs, the early and late phase distribution kinetics of MSCs following in vivo administration, the ultimate fate of MSCs following administration and the potential importance of these MSC properties to their therapeutic effects. We will critique current cellular imaging and tracking methodologies used to track exogenous MSCs and their suitability for use in patients, discuss the insights they provide into the distribution and fate of MSCs after administration, and suggest strategies by which MSC biodistribution and fate may be modulated for therapeutic effect and clinical use. In conclusion, a better understanding of patterns of biodistribution and of the fate of MSCs will add important additional safety data regarding MSCs, address regulatory requirements, and may uncover strategies to increase the distribution and/or persistence of MSC at the sites of injury, potentially increasing their therapeutic potential for multiple disorders.

中文翻译:

调节外源性 MSC 的分布和命运以增强治疗潜力:已知和未知

间充质干/基质细胞 (MSC) 正在针对几种使人衰弱的疾病进行深入的转化研究,包括 ARDS 和败血症等危重疾病。MSC 通过与宿主组织的相互作用,通过要求 MSC 靠近损伤区域的机制,发挥多种生物学效应。充分利用 MSC 等先进药物治疗产品的治疗潜力并将其成功转化为临床应用,需要详细了解 MSC 在受损组织中的分布和持久性。关键方面包括了解 MSC 在体内的分布、宿主对 MSC 给药的反应以及宿主内外源性给药的 MSC 的最终命运。影响这种相互作用的因素包括 MSC 组织来源、MSC 体外培养条件、MSC 给药途径以及与目标疾病状态相关的具体问题,每一个都有待充分表征。了解这些因素可能会产生改变 MSC 分布和命运的策略,从而增强其治疗效果。本综述将检验我们对 MSC 作用机制的理解、体内给药后 MSC 的早期和晚期分布动力学、给药后 MSC 的最终命运以及这些 MSC 特性对其治疗效果的潜在重要性。我们将批评当前用于追踪外源性 MSC 及其适用于患者的细胞成像和追踪方法,讨论它们对给药后 MSC 的分布和命运提供的见解,并提出可以调节 MSC 生物分布和命运以达到治疗效果和临床应用的策略。总之,更好地了解生物分布模式和 MSC 的命运将增加有关 MSC 的重要附加安全数据,满足监管要求,并可能揭示增加 MSC 在损伤部位的分布和/或持久性的策略,潜在地增加他们对多种疾病的治疗潜力。
更新日期:2019-07-01
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