PT  - JOURNAL ARTICLE
AU  - Laurence Guyonneau-Harmand
AU  - Bruno L’Homme
AU  - Brigitte Birebent
AU  - Christophe Desterke
AU  - Nathalie Chevallier
AU  - Loïc Garçon
AU  - Hélène Lapillonne
AU  - Marc Benderitter
AU  - François Delhommeau
AU  - Thierry Jaffredo
AU  - Alain Chapel
AU  - Luc Douay
TI  - Transgene-free hematopoietic stem and progenitor cells from human induced pluripotent stem cells
AID  - 10.1101/177691
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 177691
4099  - http://biorxiv.org/content/early/2017/08/21/177691.short
4100  - http://biorxiv.org/content/early/2017/08/21/177691.full
AB  - 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.