Department of Pediatrics, Children's Hospital at Montefiore, Bronx, New York, USA.
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, USA.
Stem Cells Transl Med. 2021 Mar;10(3):337-345. doi: 10.1002/sctm.20-0294. Epub 2020 Oct 15.
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.
造血干细胞移植（HSCT）是治疗许多恶性、先天性和获得性血液疾病的一种方法。HSCT 领域的一些突出挑战包括免疫匹配供体的缺乏、我们无法有效地在体外扩增造血干细胞（HSCs），以及植入期间的高感染风险。科学家们正在努力开发方案来体外生成、扩增和维持 HSCs，但这些方案尚未准备好用于临床应用。鉴于这些问题，深入了解 HSC 在临床前模型中的特化、调控和分化对于提高 HSCT 的治疗效果至关重要。在这篇综述中，我们通过讨论模式生物中最近的基础 HSC 研究对生物医学研究人员和移植临床医生的潜在治疗意义，将他们联系起来。我们考虑了当前 HSCT 实践中的不足，例如为成功和快速植入获得足够细胞剂量的问题、骨髓清除后巨大的炎症级联激活，以及移植物抗宿主病。此外，我们讨论了在斑马鱼、小鼠和非人类灵长类动物的临床前模型中进行的 HSC 生物学和移植领域的最新进展，这些进展可以为临床应用的新兴实践提供信息。
