Hematopoietic stem cells: transcriptional regulation, ex vivo expansion and clinical application.

Hematopoietic stem cells: transcriptional regulation, ex vivo expansion and clinical application.
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造血干细胞:转录调控,离体扩张和临床应用。

DOI:
10.2174/156652412798376125
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发表时间:
2012-01
影响因子:
2.5
通讯作者:
Das H
Das H
中科院分区:
医学4区
文献类型:
--
作者:
Aggarwal R;Lu J;Pompili VJ;Das H

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体外造血干细胞(HSC)池及其分化后代的维持受转录因子、细胞周期蛋白、细胞外基质及其微环境的复杂网络的协调调节。在了解调节造血干细胞体内静止和增殖的机制以制定体外扩增策略方面已经取得了进展。造血干细胞的体外扩增对于获得足够数量的干细胞是很重要的,并且对于患有血液疾病和恶性肿瘤的患者来说,造血干细胞移植是很容易获得的来源。我们的实验室已经建立了一种基于纳米纤维的造血干细胞体外扩增策略,同时保留了它们的干细胞特征。体外扩增细胞在各种疾病模型中也具有生物学功能。然而,扩增干细胞在临床水平上的治疗潜力仍有待验证。本文概述了调节造血干细胞发育及其功能的转录因子、调节细胞周期状态的基因、试图开发有效和高效的造血干细胞体外扩增方案的研究以及造血干细胞在各种非恶性和恶性疾病中的应用。总的来说,当前综述的目标是提供对解决限制造血干细胞在体内和体外扩张的挑战的关键因素的理解。
Maintenance of ex vivo hematopoietic stem cells (HSC) pool and its differentiated progeny is regulated by complex network of transcriptional factors, cell cycle proteins, extracellular matrix, and their microenvironment through an orchestrated fashion. Strides have been made to understand the mechanisms regulating in vivo quiescence and proliferation of HSCs to develop strategies for ex vivo expansion. Ex vivo expansion of HSCs is important to procure sufficient number of stem cells and as easily available source for HSC transplants for patients suffering from hematological disorders and malignancies. Our lab has established a nanofiber-based ex vivo expansion strategy for HSCs, while preserving their stem cell characteristics. Ex vivo expanded cells were also found biologically functional in various disease models. However, the therapeutic potential of expanded stem cells at clinical level still needs to be verified. This review outlines transcriptional factors that regulate development of HSCs and their commitment, genes that regulate cell cycle status, studies that attempt to develop an effective and efficient protocol for ex vivo expansion of HSCs and application of HSC in various non-malignant and malignant disorders. Overall the goal of the current review is to deliver an understanding of factors that are critical in resolving the challenges that limit the expansion of HSCs in vivo and ex vivo.
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