小柯机器人

日本东京大学Satoshi Yamazaki等研究人员合作实现人类造血干细胞的化学定义的无细胞因子扩增。2023年2月22日，国际知名学术期刊《自然》在线发表了这一成果。

研究人员报告了一种培养体系的建立，通过完全替代外源细胞因子、白蛋白、化学激动剂以及己内酰胺聚合物，其能够长期体外扩增人类造血干细胞（HSC）。磷酸肌醇3-激酶激活剂与血小板生成素受体激动剂和pyrimidoindole衍生物UM171的结合，足以刺激脐带血造血干细胞的扩张，从而能够在异种移植试验中连续植入。分裂克隆移植实验和单细胞RNA测序分析进一步支持体外HSC扩增。这个化学扩展培养系统将有助于推进临床造血干细胞治疗。

据悉，HSC是一种罕见的细胞类型，可以在移植后重建整个血液和免疫系统，并可作为多种血液疾病的治愈性细胞疗法。然而，体内造血干细胞数量少，使得生物学分析和临床应用都很困难，而人造血干细胞在体外扩增的有限程度仍然是造血干细胞移植这一更广泛、更安全治疗主题的重大障碍。虽然已经测试了各种试剂用于刺激人类造血干细胞的扩张，细胞因子一直被认为是支持体外造血干细胞的必要条件。

附：英文原文

Title: Chemically defined cytokine-free expansion of human haematopoietic stem cells

Author: Sakurai, Masatoshi, Ishitsuka, Kantaro, Ito, Ryoji, Wilkinson, Adam C., Kimura, Takaharu, Mizutani, Eiji, Nishikii, Hidekazu, Sudo, Kazuhiro, Becker, Hans Jiro, Takemoto, Hiroshi, Sano, Tsubasa, Kataoka, Keisuke, Takahashi, Satoshi, Nakamura, Yukio, Kent, David G., Iwama, Atsushi, Chiba, Shigeru, Okamoto, Shinichiro, Nakauchi, Hiromitsu, Yamazaki, Satoshi

Issue&Volume: 2023-02-22

Abstract: Haematopoietic stem cells (HSCs) are a rare cell type that reconstitute the entire blood and immune systems after transplantation and can be used as a curative cell therapy for a variety of haematological diseases1,2. However, the low number of HSCs in the body makes both biological analyses and clinical application difficult, and the limited extent to which human HSCs can be expanded ex vivo remains a substantial barrier to the wider and safer therapeutic use of HSC transplantation3. Although various reagents have been tested in attempts to stimulate the expansion of human HSCs, cytokines have long been thought to be essential for supporting HSCs ex vivo4. Here we report the establishment of a culture system that allows the long-term ex vivo expansion of human HSCs, achieved through the complete replacement of exogenous cytokines and albumin with chemical agonists and a caprolactam-based polymer. A phosphoinositide 3-kinase activator, in combination with a thrombopoietin-receptor agonist and the pyrimidoindole derivative UM171, were sufficient to stimulate the expansion of umbilical cord blood HSCs that are capable of serial engraftment in xenotransplantation assays. Ex vivo HSC expansion was further supported by split-clone transplantation assays and single-cell RNA-sequencing analysis. Our chemically defined expansion culture system will help to advance clinical HSC therapies.

DOI: 10.1038/s41586-023-05739-9

Source: https://www.nature.com/articles/s41586-023-05739-9

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
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