Endothelial cells promote expansion of long-term engrafting marrow hematopoietic stem and progenitor cells in primates Academic Article uri icon

Overview

MeSH Major

  • Cell Differentiation
  • Cellular Reprogramming
  • Endothelium
  • Hematopoietic Stem Cells
  • T-Lymphocytes

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.

publication date

  • March 2017

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5442761

Digital Object Identifier (DOI)

  • 10.5966/sctm.2016-0240

PubMed ID

  • 28297579

Additional Document Info

start page

  • 864

end page

  • 876

volume

  • 6

number

  • 3