Transgene-free hematopoietic stem and progenitor cells from human induced pluripotent stem cells - Migration et différenciation des cellules souches hématopoiétiques Accéder directement au contenu
Pré-Publication, Document De Travail Année : 2017

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.
Fichier principal
Vignette du fichier
Guyonneau et al.Cplte.pdf (7.43 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-01579330 , version 1 (30-08-2017)

Identifiants

Citer

Laurence Guyonneau-Harmand, Bruno L ' Homme, Brigitte Birebent, Christophe Desterke, Nathalie Chevallier, et al.. Transgene-free hematopoietic stem and progenitor cells from human induced pluripotent stem cells. 2017. ⟨hal-01579330⟩
617 Consultations
245 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More