Advantages and challenges of ex vivo generation and expansion of human hematopoietic stem cells from pluripotent stem cells.

IF 2.5 4区 医学 Q2 HEMATOLOGY Experimental hematology Pub Date : 2025-03-12 DOI:10.1016/j.exphem.2025.104752
Min Ding, Yu Lu, Quan-Kai Lei, Yun-Wen Zheng
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Abstract

Hematopoietic stem cell transplantation (HSCT) is an essential and increasing therapeutic approach for treating conditions such as leukemia, lymphoma, and other blood cancers. However, its widespread use faces significant challenges, including limited donor availability, pathogen, and the risk of immune rejection. The emergence of pluripotent stem cells (PSCs) offers a potential solution to these challenges. By enabling the generation of hematopoietic stem cell (HSCs) and blood cells in vitro, PSCs open pathways to address the limitations of traditional HSC sources. Self-induced or gene-edited PSCs from patients may provide an accessible and personalized option for clinical applications. In this review, we examine the current protocols for differentiating PSCs into HSCs and blood cells, highlighting their benefits and shortcomings. Despite advancements in this field, two primary challenges persist: low differentiation efficiency and difficulties in isolating and enriching functional HSCs. These problems make it difficult to obtain hematopoietic stem cells for long-term survival. Thus we propose innovative strategies and potential improvements including induction scheme optimization, reprogramming, and cell fate tracking. Future research should prioritize the development of efficient and reliable differentiation protocols for PSCs to obtain more functional HSCs. Additionally, establishing effective methods for enriching functional HSCs and blood cells will be critical for optimizing their use in clinical applications. These efforts hold the promise of overcoming current limitations and advancing the therapeutic potential of PSC-derived blood cells.

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造血干细胞移植(HSCT)是治疗白血病、淋巴瘤和其他血癌等疾病必不可少的治疗方法,而且越来越多。然而,造血干细胞移植的广泛应用面临着巨大挑战,包括供体有限、病原体和免疫排斥风险。多能干细胞的出现为这些挑战提供了潜在的解决方案。通过在体外生成造血干细胞和血细胞,多能干细胞为解决传统造血干细胞来源的局限性开辟了道路。来自患者的自我诱导或基因编辑的造血干细胞可为临床应用提供一种可获得的个性化选择。在这篇综述中,我们研究了将造血干细胞分化为造血干细胞和血细胞的现有方案,重点介绍了它们的优点和不足。尽管这一领域取得了进步,但仍存在两个主要挑战:分化效率低以及分离和富集功能性造血干细胞的困难。这些问题导致难以获得可长期存活的造血干细胞。因此,我们提出了创新策略和潜在的改进方案,包括诱导方案优化、重编程和细胞命运追踪。未来的研究应优先发展高效可靠的造血干细胞分化方案,以获得更多功能性造血干细胞。此外,建立富集功能性造血干细胞和血细胞的有效方法对于优化它们在临床应用中的使用至关重要。这些努力有望克服目前的局限性,并提升造血干细胞衍生血液细胞的治疗潜力。
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来源期刊
Experimental hematology
Experimental hematology 医学-血液学
CiteScore
5.30
自引率
0.00%
发文量
84
审稿时长
58 days
期刊介绍: Experimental Hematology publishes new findings, methodologies, reviews and perspectives in all areas of hematology and immune cell formation on a monthly basis that may include Special Issues on particular topics of current interest. The overall goal is to report new insights into how normal blood cells are produced, how their production is normally regulated, mechanisms that contribute to hematological diseases and new approaches to their treatment. Specific topics may include relevant developmental and aging processes, stem cell biology, analyses of intrinsic and extrinsic regulatory mechanisms, in vitro behavior of primary cells, clonal tracking, molecular and omics analyses, metabolism, epigenetics, bioengineering approaches, studies in model organisms, novel clinical observations, transplantation biology and new therapeutic avenues.
期刊最新文献
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