Long-term engrafting multilineage hematopoietic cells differentiated from human induced pluripotent stem cells
- Author(s)
- Ng, ES; Sarila, G; Li, JY; Edirisinghe, HS; Saxena, R; Sun, S; Bruveris, FF; Labonne, T; Sleebs, N; Maytum, A; Yow, RY; Inguanti, C; Motazedian, A; Calvanese, V; Capellera-Garcia, S; Ma, F; Nim, HT; Ramialison, M; Bonifer, C; Mikkola, HKA; Stanley, EG; Elefanty, AG;
- Journal Title
- Nature Biotechnology
- Publication Type
- Online publication before print
- 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.Prkdc(scid) Il2rg(tm1Wjl/SzJ) Kit(W41/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.
- Department(s)
- Laboratory Research
- Publisher's Version
- https://doi.org/10.1038/s41587-024-02360-7
- Open Access at Publisher's Site
https://doi.org/10.1038/s41587-024-02360-7- Terms of Use/Rights Notice
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Creation Date: 2024-09-19 02:48:17
Last Modified: 2024-09-19 02:49:37