Endothelial cells provide a niche for placental hematopoietic stem/progenitor cell expansion through broad transcriptomic modification

Christophe M. Raynaud, Jason M. Butler, Najeeb Halabi, Faizzan S. Ahmad, Badereldeen Ahmed, Shahin Rafii, Arash Rafii Tabrizi

Research output: Contribution to journalArticle

15 Citations (Scopus)

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-/dimCD34+CD38-CD90+) were maintained on confluent feeder layers and the number of cells and their marker expression were monitored over 21days. Although both types of feeder layers supported hematopoietic expansion, only endothelial cells triggered amplification of Lin-CD45-/dimCD34+CD38-CD90+ cells, which peaked at 14days. 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.

Original languageEnglish
Pages (from-to)1074-1090
Number of pages17
JournalStem Cell Research
Volume11
Issue number3
DOIs
Publication statusPublished - 1 Nov 2013

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Hematopoietic Stem Cells
Endothelial Cells
Feeder Cells
Fetal Blood
Stem Cells
RNA Sequence Analysis
Cell Lineage
Mesenchymal Stromal Cells
Publications
Cell Differentiation

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Medicine(all)

Cite this

Endothelial cells provide a niche for placental hematopoietic stem/progenitor cell expansion through broad transcriptomic modification. / Raynaud, Christophe M.; Butler, Jason M.; Halabi, Najeeb; Ahmad, Faizzan S.; Ahmed, Badereldeen; Rafii, Shahin; Tabrizi, Arash Rafii.

In: Stem Cell Research, Vol. 11, No. 3, 01.11.2013, p. 1074-1090.

Research output: Contribution to journalArticle

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