Advances in preclinical hematopoietic stem cell models and possible implications for improving therapeutic transplantation.
Advances in preclinical hematopoietic stem cell models and possible implications for improving therapeutic transplantation.
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临床前造血干细胞模型的研究进展及其对改善治疗性移植的潜在意义。
DOI：
10.1002/sctm.20-0294
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发表时间：
2021-03
影响因子：
6
通讯作者：
Bowman TV
中科院分区：
文献类型：
--
作者：
Fraint E;Ulloa BA;Feliz Norberto M;Potts KS;Bowman TV
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），以及植入期间的高感染风险。科学家们正在努力开发体外生成、扩增和维持HSC的方案，但这些方案尚未准备好用于临床应用。鉴于这些问题，推进我们对临床前模型中HSC的特化、调节和分化的理解对于提高HSCT的治疗效用至关重要。在这篇综述中，我们将生物医学研究人员和移植临床医生联系起来，讨论了最近在模式生物中基础HSC研究的潜在治疗意义。我们考虑了当前HSCT实践中的缺陷，例如获得足够的细胞剂量以成功和快速植入的问题，骨髓消融术后巨大的炎症级联反应激活以及移植物抗宿主病。此外，我们还讨论了在斑马鱼、小鼠和非人灵长类动物的临床前模型中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。 临床（已建立）和临床前（理论）进展为规避当前造血干细胞移植（HSCT）限制提供了治疗选择，包括移植后感染，低HSC供体供应，炎症和移植物抗宿主病（GVHD）。本文综述了临床前造血干细胞模型的研究进展及其对改善治疗性移植的可能意义。
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. Clinical (established) and preclinical (theoretical) advances are informing treatment options for circumventing current hematopoietic stem cell transplantation (HSCT) limitations including post‐transplant infection, low HSC donor supply, inflammation, and graft‐vs‐host disease (GVHD). This review covers the advances in preclinical hematopoietic stem cell models and possible implications for improving therapeutic transplantation.
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影响因子：
6
作者：
Gori JL;Butler JM;Kunar B;Poulos MG;Ginsberg M;Nolan DJ;Norgaard ZK;Adair JE;Rafii S;Kiem HP
通讯作者：
Kiem HP
影响因子：
23.9
作者：
George, Benson M.;Kao, Kevin S.;Weissman, Irving L.
通讯作者：
Weissman, Irving L.
影响因子：
21.3
作者：
Henninger, Jonathan;Santoso, Buyung;Zon, Leonard
通讯作者：
Zon, Leonard
影响因子：
64.8
作者：
Busch, Katrin;Klapproth, Kay;Rodewald, Hans-Reimer
通讯作者：
Rodewald, Hans-Reimer
影响因子：
23.9
作者：
Dykstra, Brad;Kent, David;Eaves, Connie
通讯作者：
Eaves, Connie