Vascular Platform to Define Hematopoietic Stem Cell Factors and Enhance Regenerative Hematopoiesis

Stem Cell Reports. 2015 Nov 10;5(5):881-894. doi: 10.1016/j.stemcr.2015.08.018. Epub 2015 Oct 1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Endothelial Progenitor Cells / cytology*
  • Endothelial Progenitor Cells / metabolism
  • Endothelial Progenitor Cells / transplantation
  • Hematopoiesis*
  • Mice
  • Mice, Inbred C57BL
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Stem Cell Niche*
  • Stromal Cells / cytology
  • Stromal Cells / metabolism
  • Stromal Cells / transplantation

Substances

  • Cytokines
  • Akt1 protein, mouse
  • Proto-Oncogene Proteins c-akt