Sugiyama-Finnis Ayano, Yamazaki Satoshi
Division of Cell Regulation, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, 108-8639, Japan.
Regen Ther. 2025 Jul 17;30:403-414. doi: 10.1016/j.reth.2025.07.001. eCollection 2025 Dec.
Stem-cell derived therapies are an essential pillar in the field of regenerative medicine, utilising stem cell self-renewal and multipotent or pluripotent differentiation capabilities to give rise to functional, specialised cells to repair and restore tissue function. Haematopoietic cell therapies have been pivotal to the development of the regenerative medicine field and continue to hold significant promise enabled by recent technical innovation in cell culture approaches that have expanded their therapeutic potential. The development of novel cell culture protocols that allow for the standardised ex vivo expansion of haematopoietic stem cells (HSCs) has facilitated the exploration of umbilical cord blood allogeneic HSC transplantation. Directed differentiation protocols of HSCs, embryonic stem cells and induced pluripotent stem cells, to selectively produce a desired haematopoietic cell type in a donor-independent manner, has broadened the scope for haematopoietic cell-based regenerative therapy. Furthermore, the integration of genome modification or gene editing with these protocols have allowed for corrective autologous HSC transplantation as well as the ability to confer haematopoietic cells with enhanced or novel therapeutic functions. Despite this, realising large-scale clinical translation remains challenging. Current efforts aim to move towards chemically defined culture systems, improving the efficiency and reproducibility of lineage-specific differentiation with an emphasis on compatibility with genome modification and gene-editing protocols for the scalable production of high-quality, efficacious and safe cellular therapies. In this review, we summarise the key milestones and technical advancements in the field in addition to the outstanding questions to be addressed.
干细胞衍生疗法是再生医学领域的重要支柱，它利用干细胞的自我更新以及多能或全能分化能力，产生功能性的特化细胞，以修复和恢复组织功能。造血细胞疗法一直是再生医学领域发展的关键，并因细胞培养方法的最新技术创新而继续具有巨大潜力，这些创新扩大了其治疗潜力。新型细胞培养方案的开发使得造血干细胞（HSC）能够在体外标准化扩增，这促进了脐带血同种异体HSC移植的探索。HSC、胚胎干细胞和诱导多能干细胞的定向分化方案能够以不依赖供体的方式选择性地产生所需的造血细胞类型，拓宽了基于造血细胞的再生治疗范围。此外，将基因组修饰或基因编辑与这些方案相结合，实现了自体HSC的矫正移植，并赋予造血细胞增强的或新的治疗功能。尽管如此，实现大规模临床转化仍然具有挑战性。目前的努力旨在转向化学成分明确的培养系统，提高谱系特异性分化的效率和可重复性，同时强调与基因组修饰和基因编辑方案的兼容性，以实现高质量、有效和安全的细胞疗法的可扩展生产。在这篇综述中，我们总结了该领域的关键里程碑和技术进展以及有待解决的突出问题。
