法国EFS细胞工程与治疗中心Thierry Jaffredo和索邦大学Laurence Guyonneau-Harmand课题组，合作利用诱导人多能干细胞生成了无转基因造血干细胞（HSCs）。2023年12月7日，国际学术期刊《细胞-干细胞》发表了这一成果。

研究人员利用独创的一步培养系统，通过分化人诱导多能干细胞（hiPSCs），获得了无载体、无基质的可移植造血干细胞。注射到免疫功能低下小鼠体内后，hiPSCs衍生的细胞会在骨髓中定居，并形成可连续移植的强大多系造血群体。单细胞RNA测序结果表明，这种再植活性是由与人类胚胎主动脉来源造血干细胞转录相似的造血群体产生。

总之，该研究结果表明hiPSCs能生成造血干细胞，并将有助于揭示人类发育过程中造血干细胞生成的关键调节因子。

研究人员表示，HSCs是造血细胞（HC）移植产生终身疗效的稀有细胞。近几十年来，对临床级造血干细胞的需求大幅增加，导致患者治疗面临困难。利用多能干细胞生成造血干细胞是一个前景广阔但尚未实现的目标。

附：英文原文

Title: Generation of transgene-free hematopoietic stem cells from human induced pluripotent stem cells

Author: Olivier Piau, Mathias Brunet-Manquat, Bruno L’Homme, Laurence Petit, Brigitte Birebent, Christine Linard, Laetitia Moeckes, Thomas Zuliani, Hélène Lapillonne, Marc Benderitter, Luc Douay, Alain Chapel, Laurence Guyonneau-Harmand, Thierry Jaffredo

Issue&Volume: 2023/12/07

Abstract: Hematopoietic stem cells (HSCs) are the rare cells responsible for the lifelong curativeeffects of hematopoietic cell (HC) transplantation. The demand for clinical-gradeHSCs has increased significantly in recent decades, leading to major difficultiesin treating patients. A promising but not yet achieved goal is the generation of HSCsfrom pluripotent stem cells. Here, we have obtained vector- and stroma-free transplantableHSCs by differentiating human induced pluripotent stem cells (hiPSCs) using an originalone-step culture system. After injection into immunocompromised mice, cells derivedfrom hiPSCs settle in the bone marrow and form a robust multilineage hematopoieticpopulation that can be serially transplanted. Single-cell RNA sequencing shows thatthis repopulating activity is due to a hematopoietic population that is transcriptionallysimilar to human embryonic aorta-derived HSCs. Overall, our results demonstrate thegeneration of HSCs from hiPSCs and will help identify key regulators of HSC productionduring human ontogeny.

DOI: 10.1016/j.stem.2023.11.002

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00394-6