Endothelial cells provide a niche for placental hematopoietic stem/progenitor cell expansion through broad transcriptomic modification. Academic Article uri icon

Overview

MeSH

  • Animals
  • Antigens, CD34
  • Antigens, CD45
  • Cell Communication
  • Cell Differentiation
  • Cell Lineage
  • Cells, Cultured
  • Female
  • Fetal Blood
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Mice
  • Pregnancy
  • Signal Transduction
  • Stem Cell Niche

MeSH Major

  • Endothelial Cells
  • Hematopoietic Stem Cells
  • Placenta
  • Transcriptome

abstract

  • Umbilical cord blood (UCB) is an attractive source of hematopoietic stem cells (HSCs). However, the number of HSCs in UCB is limited, and attempts to amplify them in vitro remain inefficient. Several publications have documented amplification of hematopoietic stem/progenitor cells (HSPCs) on endothelial or mesenchymal cells, but the lack of homogeneity in culture conditions and HSC definition impairs direct comparison of these results. We investigated the ability of different feeder layers, mesenchymal progenitors (MPs) and endothelial cells (ECs), to amplify hematopoietic stem/progenitor cells. Placental derived HSPCs (defined as Lin(-)CD45(-/dim)CD34(+)CD38(-)CD90(+)) were maintained on confluent feeder layers and the number of cells and their marker expression were monitored over 21 days. Although both types of feeder layers supported hematopoietic expansion, only endothelial cells triggered amplification of Lin(-)CD45(-/dim)CD34(+)CD38(-)CD90(+) cells, which peaked at 14 days. The amplified cells differentiated into all cell lineages, as attested by in vitro colony-forming assays, and were capable of engraftment and multi-lineage differentiation in sub-lethally irradiated mice. Mesenchymal progenitors promoted amplification of CD38(+) cells, previously defined as precursors with more limited differentiation potential. A competitive assay demonstrated that hematopoietic stem/progenitor cells had a preference for interacting with endothelial cells in vitro. Cytokine and transcriptomic analysis of both feeder cell types identified differences in gene expression that correlated with propensity of ECs and MPs to support hematopoietic cell amplification and differentiation respectively. Finally, we used RNA sequencing of endothelial cells and HSPCs to uncover relevant networks illustrating the complex interaction between endothelial cells and HSPCs leading to stem/progenitor cell expansion. © 2013.

publication date

  • November 2013

has subject area

  • Animals
  • Antigens, CD34
  • Antigens, CD45
  • Cell Communication
  • Cell Differentiation
  • Cell Lineage
  • Cells, Cultured
  • Endothelial Cells
  • Female
  • Fetal Blood
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells
  • Humans
  • Mice
  • Placenta
  • Pregnancy
  • Signal Transduction
  • Stem Cell Niche
  • Transcriptome

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.scr.2013.07.010

PubMed ID

  • 23978474

Additional Document Info

start page

  • 1074

end page

  • 1090

volume

  • 11

number

  • 3