Vascular Platform to Define Hematopoietic Stem Cell Factors and Enhance Regenerative Hematopoiesis. Academic Article uri icon

Overview

MeSH

  • Animals
  • Cytokines
  • Mice
  • Mice, Inbred C57BL
  • Proto-Oncogene Proteins c-akt
  • Stromal Cells

MeSH Major

  • Endothelial Progenitor Cells
  • Hematopoiesis
  • Stem Cell Niche

abstract

  • Hematopoietic stem cells (HSCs) inhabit distinct microenvironments within the adult bone marrow (BM), which govern the delicate balance between HSC quiescence, self-renewal, and differentiation. Previous reports have proposed that HSCs localize to the vascular niche, comprised of endothelium and tightly associated perivascular cells. Herein, we examine the capacity of BM endothelial cells (BMECs) to support ex vivo and in vivo hematopoiesis. We demonstrate that AKT1-activated BMECs (BMEC-Akt1) have a unique transcription factor/cytokine profile that supports functional HSCs in lieu of complex serum and cytokine supplementation. Additionally, transplantation of BMEC-Akt1 cells enhanced regenerative hematopoiesis following myeloablative irradiation. These data demonstrate that BMEC-Akt1 cultures can be used as a platform for the discovery of pro-HSC factors and justify the utility of BMECs as a cellular therapy. This technical advance may lead to the development of therapies designed to decrease pancytopenias associated with myeloablative regimens used to treat a wide array of disease states. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

publication date

  • November 10, 2015

has subject area

  • Animals
  • Cytokines
  • Endothelial Progenitor Cells
  • Hematopoiesis
  • Mice
  • Mice, Inbred C57BL
  • Proto-Oncogene Proteins c-akt
  • Stem Cell Niche
  • Stromal Cells

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4649106

Digital Object Identifier (DOI)

  • 10.1016/j.stemcr.2015.08.018

PubMed ID

  • 26441307

Additional Document Info

start page

  • 881

end page

  • 894

volume

  • 5

number

  • 5