Regenerative stromal cell therapy in allogeneic hematopoietic stem cell transplantation: current impact and future directions.
Regenerative stromal cell therapy in allogeneic hematopoietic stem cell transplantation: current impact and future directions.
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DOI：
10.1016/j.bbmt.2009.12.005
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发表时间：
2010-07
影响因子：
4.3
通讯作者：
van't Hof, Wouter
中科院分区：
文献类型：
--
作者：
Auletta, Jeffery J.;Cooke, Kenneth R.;Solchaga, Luis A.;Deans, Robert J.;van't Hof, Wouter
关键词：
再生基质细胞疗法(RSCT)有望成为预防和治疗异基因造血干细胞移植(HSCT)受者急性移植物抗宿主病(GVHD)的新方法。然而，由于有限的临床数据和体内作用机制的不明确，人们对将RSCT用于异基因HSCT的热情有所减弱。因此，RSCT在支持造血重建和治疗GVHD方面的全部临床潜力仍有待确定。本文综述了在异基因造血干细胞移植的临床前模型中再生基质细胞的免疫调节活性，并强调了一项新的文献，即微环境影响RSC的激活和功能。了解这一关键发现可能最终确定RSCT在异基因HSCT中的适当利基。特别是，需要机制研究来描述RSCT在体内对与异基因HSCT相关的炎症和损伤的影响，并确定RSC与移植受者免疫细胞相互作用的相关部位。此外，发展体内成像技术来关联生物分布模式、预期的RSC效应和临床结果将是建立剂量-反应效应和最小生物剂量阈值的关键，这些效应和最小生物剂量阈值是推进GVHD等并发症的转化性治疗策略所需的。
Regenerative stromal cell therapy (RSCT) has the potential to become a novel therapy for preventing and treating acute graft-versus-host disease (GVHD) in the allogeneic hematopoietic stem cell transplant (HSCT) recipient. However, enthusiasm for using RSCT in allogeneic HSCT has been tempered by limited clinical data and poorly-defined in vivo mechanisms of action. As a result, the full clinical potential of RSCT in supporting hematopoietic reconstitution and as treatment for GVHD remains to be determined. This manuscript reviews the immunomodulatory activity of regenerative stromal cells in pre-clinical models of allogeneic HSCT and emphasizes an emerging literature suggesting that microenvironment influences RSC activation and function. Understanding this key finding may ultimately define the proper niche for RSCT in allogeneic HSCT. In particular, mechanistic studies are needed to delineate the in vivo effects of RSCT in response to inflammation and injury associated with allogeneic HSCT and to define the relevant sites of RSC interaction with immune cells in the transplant recipient. Furthermore, development of in vivo imaging technology to correlate biodistribution patterns, desired RSC effect, and clinical outcome will be crucial to establishing dose-response effects and minimal biologic-dose thresholds needed to advance translational treatment strategies for complications like GVHD.
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