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

TitleVascular Platform to Define Hematopoietic Stem Cell Factors and Enhance Regenerative Hematopoiesis.
Publication TypeJournal Article
Year of Publication2015
AuthorsPoulos MG, Crowley MJP, Gutkin MC, Ramalingam P, Schachterle W, Thomas J-L, Elemento O, Butler JM
JournalStem Cell Reports
Volume5
Issue5
Pagination881-894
Date Published2015 Nov 10
ISSN2213-6711
KeywordsAnimals, Cytokines, Endothelial Progenitor Cells, Hematopoiesis, Mice, Mice, Inbred C57BL, Proto-Oncogene Proteins c-akt, Stem Cell Niche, Stromal Cells
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.

DOI10.1016/j.stemcr.2015.08.018
Alternate JournalStem Cell Reports
PubMed ID26441307
PubMed Central IDPMC4649106