Transgene-free hematopoietic stem and progenitor cells from human induced pluripotent stem cells
Résumé
The successful production of Hematopoietic Stem and Progenitor Cells (HSPCs) from
human pluripotent sources is conditioned by transgene delivery1-5. We describe here a dedicated
and tractable one step, GMP-grade, transgene-free and stroma-free protocol to produce HSPCs from
human induced pluripotent stem cells (hiPSCs). This procedure, applied to several sources of hiPSCs
with equal efficiency, is based on a directed differentiation with morphogens and cytokines to
generate a cell population close to nascent HSPCs or their immediate forerunners i.e., hemogenic
endothelial cells6-9. Following engraftment into immunocompromised recipients, this cell population
was proved capable of a robust myeloid, lymphoid and definitive red blood cell production in
sequential recipients for at least 40 weeks. Further identification of the repopulating cells show that
they express the G protein–coupled receptor APELIN (APLNR) and the homing receptor CXCR4.
This demonstrates that the generation of bona fide HSPCs from hiPSCs without transgenes is
possible and passes through an early endo-hematopoietic intermediate. This work opens the way to
the generation of clinical grade HSPCs for the treatment of hematological diseases and holds promise
for the analysis of HSPC development in the human species.
| Origine | Fichiers produits par l'(les) auteur(s) |
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