Hematopoietic stem cells from pluripotent stem cells: Clinical potential, challenges, and future perspectives.

Hematopoietic stem cells from pluripotent stem cells: Clinical potential, challenges, and future perspectives.
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来自多能干细胞的造血干细胞:临床潜力,挑战和未来前景。

DOI:
10.1002/sctm.20-0247
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发表时间:
2020-12
影响因子:
6
通讯作者:
Tisdale JF
Tisdale JF
中科院分区:
医学2区
文献类型:
--
作者:
Demirci S;Leonard A;Tisdale JF

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从诱导的多能干细胞(IPSCs)中诱导出造血干细胞(HSCs)是一个活跃而有前途的研究领域,然而,产生可植入的HSCs仍然是一个主要的障碍。从IPSCs等可再生来源体外获得的HSC为研究发育中的造血、疾病模型和药物发现提供了一种实验工具,并为恶性和非恶性血液病提供了巨大的治疗潜力。虽然最初的尝试大多是无法植入的卵黄囊原始/最终造血,但最近的进展表明,利用异位转录因子表达从IPSCs获得可植入的HSC是可行的。新的HSC生成的战略发展包括对HSC个体发育的进一步研究,以及对关键信号通路、表观遗传调控、HSC和IPSC微环境以及有助于干细胞生物学和功能的细胞-细胞相互作用的阐明。为患者特定的造血干细胞(HSC)或从诱导的多能干细胞(IPSCs)生成血液产品提供潜在的未来临床环境。
The generation of hematopoietic stem cells (HSCs) from induced pluripotent stem cells (iPSCs) is an active and promising area of research; however, generating engraftable HSCs remains a major obstacle. Ex vivo HSC derivation from renewable sources such as iPSCs offers an experimental tool for studying developmental hematopoiesis, disease modeling, and drug discovery, and yields tremendous therapeutic potential for malignant and nonmalignant hematological disorders. Although initial attempts mostly recapitulated yolk sac primitive/definitive hematopoiesis with inability to engraft, recent advances suggest the feasibility of engraftable HSC derivation from iPSCs utilizing ectopic transcription factor expression. Strategic development for de novo HSC generation includes further investigations of HSC ontogeny, and elucidation of critical signaling pathways, epigenetic modulations, HSC and iPSC microenvironment, and cell‐cell interactions that contribute to stem cell biology and function. A potential future clinical setting for patient‐specific hematopoietic stem cell (HSC) or blood product generation from induced pluripotent stem cells (iPSCs).
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