Hematopoietic stem cell transplantation (HSCT) is a treatment for many malignant, congenital, and acquired hematologic diseases. Some outstanding challenges in the HSCT field include the paucity of immunologically‐matched donors, our inability to effectively expand hematopoeitic stem cells (HSCs) ex vivo, and the high infection risk during engraftment. Scientists are striving to develop protocols to generate, expand, and maintain HSCs ex vivo, however these are not yet ready for clinical application. Given these problems, advancing our understanding of HSC specification, regulation, and differentiation in preclinical models is essential to improve the therapeutic utility of HSCT. In this review, we link biomedical researchers and transplantation clinicians by discussing the potential therapeutic implications of recent fundamental HSC research in model organisms. We consider deficiencies in current HSCT practice, such as problems achieving adequate cell dose for successful and rapid engraftment, immense inflammatory cascade activation after myeloablation, and graft‐vs‐host disease. Furthermore, we discuss recent advances in the field of HSC biology and transplantation made in preclinical models of zebrafish, mouse, and nonhuman primates that could inform emerging practice for clinical application.

中文翻译：

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临床前造血干细胞模型的进展及其对改善治疗性移植的可能意义

造血干细胞移植 (HSCT) 是一种治疗许多恶性、先天性和获得性血液疾病的方法。HSCT 领域的一些突出挑战包括缺乏免疫匹配的供体、我们无法有效地体外扩增造血干细胞 (HSC) 以及移植过程中的高感染风险。科学家们正在努力开发在体外生成、扩展和维护 HSC 的协议，但是这些还没有准备好用于临床应用。鉴于这些问题，提高我们对临床前模型中 HSC 规范、调节和分化的理解对于提高 HSCT 的治疗效用至关重要。在本次审查中，我们通过讨论最近对模型生物的基础 HSC 研究的潜在治疗意义，将生物医学研究人员和移植临床医生联系起来。我们考虑了当前 HSCT 实践中的缺陷，例如实现成功和快速植入所需的足够细胞剂量的问题、清髓后巨大的炎症级联激活以及移植物抗宿主病。此外，我们讨论了 HSC 生物学和移植领域的最新进展，这些进展在斑马鱼、小鼠和非人类灵长类动物的临床前模型中取得，这些进展可以为临床应用的新兴实践提供信息。