Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Transgene-free hematopoietic stem and progenitor cells from human induced pluripotent stem cells

Laurence Guyonneau-Harmand, Bruno L’Homme, Brigitte Birebent, Christophe Desterke, Nathalie Chevallier, Loïc Garçon, Hélène Lapillonne, Marc Benderitter, François Delhommeau, Thierry Jaffredo, Alain Chapel, Luc Douay
doi: https://doi.org/10.1101/177691
Laurence Guyonneau-Harmand
1UPMC Univ Paris 06, UMR_S938 CDR Saint-Antoine, Prolifération et Différenciation des Cellules Souches, F-75012 Paris, France
2INSERM, UMR_S938, Prolifération et Différenciation des Cellules Souches, F-75012 Paris, France
3EFS Ile de France, Unité d’Ingénierie et de Thérapie Cellulaire, Créteil, F-94017, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bruno L’Homme
4IRSN, PRP-HOM, SRBE, Laboratoire de recherche en régénération des tissus sains irradiés (LR2I), F-92262 Fontenay-aux-Roses, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brigitte Birebent
3EFS Ile de France, Unité d’Ingénierie et de Thérapie Cellulaire, Créteil, F-94017, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christophe Desterke
5University Paris Sud 11, UFR Medecine, Villejuif FRANCE
6INSERM Unit UMS-33, bioinformatics plateform, Villejuif FRANCE
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nathalie Chevallier
3EFS Ile de France, Unité d’Ingénierie et de Thérapie Cellulaire, Créteil, F-94017, France
7Institut Mondor de Recherche Biomédicale, INSERM U955-E10, Créteil, France
8Université Paris Est, Faculté de Medecine, Créteil, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Loïc Garçon
1UPMC Univ Paris 06, UMR_S938 CDR Saint-Antoine, Prolifération et Différenciation des Cellules Souches, F-75012 Paris, France
2INSERM, UMR_S938, Prolifération et Différenciation des Cellules Souches, F-75012 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hélène Lapillonne
1UPMC Univ Paris 06, UMR_S938 CDR Saint-Antoine, Prolifération et Différenciation des Cellules Souches, F-75012 Paris, France
2INSERM, UMR_S938, Prolifération et Différenciation des Cellules Souches, F-75012 Paris, France
9AP-HP, Hôpital St Antoine/Trousseau, Service d’Hématologie Biologique, F-75012 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marc Benderitter
4IRSN, PRP-HOM, SRBE, Laboratoire de recherche en régénération des tissus sains irradiés (LR2I), F-92262 Fontenay-aux-Roses, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
François Delhommeau
1UPMC Univ Paris 06, UMR_S938 CDR Saint-Antoine, Prolifération et Différenciation des Cellules Souches, F-75012 Paris, France
2INSERM, UMR_S938, Prolifération et Différenciation des Cellules Souches, F-75012 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thierry Jaffredo
10Sorbonne Universités, UPMC Univ Paris 06, CNRS UMR7622, Inserm U 1156, IBPS, Laboratoire de Biologie du Développement; 75005 Paris
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: thierry.jaffredo@upmc.fr alain.chapel@irsn.fr
Alain Chapel
1UPMC Univ Paris 06, UMR_S938 CDR Saint-Antoine, Prolifération et Différenciation des Cellules Souches, F-75012 Paris, France
2INSERM, UMR_S938, Prolifération et Différenciation des Cellules Souches, F-75012 Paris, France
4IRSN, PRP-HOM, SRBE, Laboratoire de recherche en régénération des tissus sains irradiés (LR2I), F-92262 Fontenay-aux-Roses, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: thierry.jaffredo@upmc.fr alain.chapel@irsn.fr
Luc Douay
1UPMC Univ Paris 06, UMR_S938 CDR Saint-Antoine, Prolifération et Différenciation des Cellules Souches, F-75012 Paris, France
2INSERM, UMR_S938, Prolifération et Différenciation des Cellules Souches, F-75012 Paris, France
3EFS Ile de France, Unité d’Ingénierie et de Thérapie Cellulaire, Créteil, F-94017, France
9AP-HP, Hôpital St Antoine/Trousseau, Service d’Hématologie Biologique, F-75012 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Introductory paragraph

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.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted August 21, 2017.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Transgene-free hematopoietic stem and progenitor cells from human induced pluripotent stem cells
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Transgene-free hematopoietic stem and progenitor cells from human induced pluripotent stem cells
Laurence Guyonneau-Harmand, Bruno L’Homme, Brigitte Birebent, Christophe Desterke, Nathalie Chevallier, Loïc Garçon, Hélène Lapillonne, Marc Benderitter, François Delhommeau, Thierry Jaffredo, Alain Chapel, Luc Douay
bioRxiv 177691; doi: https://doi.org/10.1101/177691
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Transgene-free hematopoietic stem and progenitor cells from human induced pluripotent stem cells
Laurence Guyonneau-Harmand, Bruno L’Homme, Brigitte Birebent, Christophe Desterke, Nathalie Chevallier, Loïc Garçon, Hélène Lapillonne, Marc Benderitter, François Delhommeau, Thierry Jaffredo, Alain Chapel, Luc Douay
bioRxiv 177691; doi: https://doi.org/10.1101/177691

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cell Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4229)
  • Biochemistry (9108)
  • Bioengineering (6752)
  • Bioinformatics (23944)
  • Biophysics (12098)
  • Cancer Biology (9497)
  • Cell Biology (13742)
  • Clinical Trials (138)
  • Developmental Biology (7616)
  • Ecology (11662)
  • Epidemiology (2066)
  • Evolutionary Biology (15479)
  • Genetics (10620)
  • Genomics (14297)
  • Immunology (9465)
  • Microbiology (22793)
  • Molecular Biology (9078)
  • Neuroscience (48890)
  • Paleontology (355)
  • Pathology (1479)
  • Pharmacology and Toxicology (2565)
  • Physiology (3823)
  • Plant Biology (8309)
  • Scientific Communication and Education (1467)
  • Synthetic Biology (2290)
  • Systems Biology (6172)
  • Zoology (1297)