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  • PMID: 27742844 was deleted because it is a duplicate of PMID: 28297579
Stem Cells Transl Med. 2017 Mar;6(3):864-876. doi: 10.5966/sctm.2016-0240. Epub 2016 Oct 14.

Endothelial Cells Promote Expansion of Long-Term Engrafting Marrow Hematopoietic Stem and Progenitor Cells in Primates.

Gori JL1, Butler JM2,3,4,5, Kunar B2,3,4,5,6, Poulos MG2,3,4,5, Ginsberg M7, Nolan DJ7, Norgaard ZK1, Adair JE1, Rafii S2,3,4, Kiem HP1,8,9.

Author information

1
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
2
Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
3
Ansary Stem Cell Institute, Weill Cornell Medical College, New York, New York, USA.
4
Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA.
5
Department of Surgery, Weill Cornell Medical College, New York, New York, USA.
6
Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medical College, New York, New York, USA.
7
Angiocrine Bioscience, New York, New York, USA.
8
Department of Medicine, University of Washington, Seattle, Washington, USA.
9
Department of Pathology, University of Washington, Seattle, Washington, USA.

Abstract

Successful expansion of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) would benefit many HSPC transplantation and gene therapy/editing applications. However, current expansion technologies have been limited by a loss of multipotency and self-renewal properties ex vivo. We hypothesized that an ex vivo vascular niche would provide prohematopoietic signals to expand HSPCs while maintaining multipotency and self-renewal. To test this hypothesis, BM autologous CD34+ cells were expanded in endothelial cell (EC) coculture and transplanted in nonhuman primates. CD34+ C38- HSPCs cocultured with ECs expanded up to 17-fold, with a significant increase in hematopoietic colony-forming activity compared with cells cultured with cytokines alone (colony-forming unit-granulocyte-erythroid-macrophage-monocyte; p < .005). BM CD34+ cells that were transduced with green fluorescent protein lentivirus vector and expanded on ECs engrafted long term with multilineage polyclonal reconstitution. Gene marking was observed in granulocytes, lymphocytes, platelets, and erythrocytes. Whole transcriptome analysis indicated that EC coculture altered the expression profile of 75 genes in the BM CD34+ cells without impeding the long-term engraftment potential. These findings show that an ex vivo vascular niche is an effective platform for expansion of adult BM HSPCs. Stem Cells Translational Medicine 2017;6:864-876.

KEYWORDS:

Bone marrow transplantation; CD34+ cells; Endothelial cells; Gene therapy; Hematopoietic stem progenitor cell

PMID:
28297579
PMCID:
PMC5442761
DOI:
10.5966/sctm.2016-0240
[Indexed for MEDLINE]

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