澳大利亚墨尔本大学Andrew G. Elefanty等研究人员合作发现，从人类诱导多能干细胞分化出的多谱系血液细胞可长期移植并具有持续造血功能。相关论文于2024年9月2日在线发表在《自然—生物技术》杂志上。

研究人员确定了一种分化条件，能够在免疫缺陷的NOD,B6.Prkdc^scid Il2rg^tm1Wjl/SzJ Kit^W41/W41小鼠中产生具有强大长期多系移植能力的造血干细胞（HSC）。

研究人员将作为类胚体的诱导多能干细胞（iPS细胞）在补充了醋酸视黄酯的特定培养基中引导分化，通过HOXA模式的中胚层向由骨形态发生蛋白4和血管内皮生长因子（VEGF）指定的造血内皮过渡。移除VEGF促进了有效的内皮向造血过渡，表现为CD34⁺血液细胞释放到培养基中，这些细胞被冷冻保存。

研究人员将200万从四个独立iPS细胞系分化出的解冻CD34⁺细胞进行静脉移植，在25%-50%的免疫缺陷受体小鼠中产生了多系骨髓移植。这些功能上定义的多能CD34⁺造血细胞，被命名为iPS细胞衍生的HSC（iHSC），其移植水平与脐带血移植后达到的水平相似。该研究为实现生成用于临床转化的HSC迈出了重要一步。

据悉，从人类iPS细胞衍生的HSC具有重要的生物医学应用价值。

附：英文原文

Title: Long-term engrafting multilineage hematopoietic cells differentiated from human induced pluripotent stem cells

Author: Ng, Elizabeth S., Sarila, Gulcan, Li, Jacky Y., Edirisinghe, Hasindu S., Saxena, Ritika, Sun, Shicheng, Bruveris, Freya F., Labonne, Tanya, Sleebs, Nerida, Maytum, Alexander, Yow, Raymond Y., Inguanti, Chantelle, Motazedian, Ali, Calvanese, Vincenzo, Capellera-Garcia, Sandra, Ma, Feiyang, Nim, Hieu T., Ramialison, Mirana, Bonifer, Constanze, Mikkola, Hanna K. A., Stanley, Edouard G., Elefanty, Andrew G.

Issue&Volume: 2024-09-02

Abstract: Hematopoietic stem cells (HSCs) derived from human induced pluripotent stem cells (iPS cells) have important biomedical applications. We identified differentiation conditions that generate HSCs defined by robust long-term multilineage engraftment in immune-deficient NOD,B6.Prkdcscid Il2rgtm1Wjl/SzJ KitW41/W41 mice. We guided differentiating iPS cells, as embryoid bodies in a defined culture medium supplemented with retinyl acetate, through HOXA-patterned mesoderm to hemogenic endothelium specified by bone morphogenetic protein 4 and vascular endothelial growth factor (VEGF). Removal of VEGF facilitated an efficient endothelial-to-hematopoietic transition, evidenced by release into the culture medium of CD34+ blood cells, which were cryopreserved. Intravenous transplantation of two million thawed CD34+ cells differentiated from four independent iPS cell lines produced multilineage bone marrow engraftment in 25–50% of immune-deficient recipient mice. These functionally defined, multipotent CD34+ hematopoietic cells, designated iPS cell-derived HSCs (iHSCs), produced levels of engraftment similar to those achieved following umbilical cord blood transplantation. Our study provides a step toward the goal of generating HSCs for clinical translation.

DOI: 10.1038/s41587-024-02360-7

Source: https://www.nature.com/articles/s41587-024-02360-7