Title | Vascular Platform to Define Hematopoietic Stem Cell Factors and Enhance Regenerative Hematopoiesis. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Poulos MG, Crowley MJP, Gutkin MC, Ramalingam P, Schachterle W, Thomas J-L, Elemento O, Butler JM |
Journal | Stem Cell Reports |
Volume | 5 |
Issue | 5 |
Pagination | 881-894 |
Date Published | 2015 Nov 10 |
ISSN | 2213-6711 |
Keywords | Animals, 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. |
DOI | 10.1016/j.stemcr.2015.08.018 |
Alternate Journal | Stem Cell Reports |
PubMed ID | 26441307 |
PubMed Central ID | PMC4649106 |