Cellular and Molecular Therapeutics Branch, National Heart Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Cells. 2023 Jan 14;12(2):321. doi: 10.3390/cells12020321.
The ability to manufacture human hematopoietic stem cells (HSCs) in the laboratory holds enormous promise for cellular therapy of human blood diseases. Several differentiation protocols have been developed to facilitate the emergence of HSCs from human pluripotent stem cells (PSCs). Most approaches employ a stepwise addition of cytokines and morphogens to recapitulate the natural developmental process. However, these protocols globally lack clinical relevance and uniformly induce PSCs to produce hematopoietic progenitors with embryonic features and limited engraftment and differentiation capabilities. This review examines how key intrinsic cues and extrinsic environmental inputs have been integrated within human PSC differentiation protocols to enhance the emergence of definitive hematopoiesis and how advances in genomics set the stage for imminent breakthroughs in this field.
在实验室中制造人类造血干细胞 (HSCs) 为人类血液疾病的细胞治疗带来了巨大的希望。已经开发了几种分化方案来促进 HSCs 从人类多能干细胞 (PSCs) 中出现。大多数方法采用逐步添加细胞因子和形态发生素来再现自然发育过程。然而，这些方案在全球范围内缺乏临床相关性，并一致诱导 PSCs 产生具有胚胎特征和有限植入和分化能力的造血祖细胞。这篇综述考察了如何在人类 PSC 分化方案中整合关键的内在线索和外在环境输入，以增强确定性造血的出现，以及基因组学的进步如何为该领域的即将突破奠定基础。
