title: Vascular Platform to Define Hematopoietic Stem Cell Factors and Enhance Regenerative Hematopoiesis.
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.
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA; Department of Surgery, Weill Cornell Medical College, New York, NY, 10065 USA; Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Poulos
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA; Department of Surgery, Weill Cornell Medical College, New York, NY, 10065 USA; Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Michael J P
authors.initials: MJP
authors.lastname: Crowley
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA; Department of Surgery, Weill Cornell Medical College, New York, NY, 10065 USA; Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Gutkin
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA; Department of Surgery, Weill Cornell Medical College, New York, NY, 10065 USA; Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Ramalingam
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA; Department of Surgery, Weill Cornell Medical College, New York, NY, 10065 USA; Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: William
authors.initials: W
authors.lastname: Schachterle
authors.affiliation: Yale Stem Cell Center, Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA; Université Pierre and Marie Curie-Paris 6, 75013 Paris, France; INSERM/CNRS U-1127/UMR-7225, 75013 Paris, France; APHP, Groupe Hospitalier Pitié-Salpètrière, 75013 Paris, France.
authors.forename: Jean-Leon
authors.initials: JL
authors.lastname: Thomas
authors.affiliation: HRH Prince Alwaleed Bin Talal Bin Abdulaziz Al-Saud Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: Elemento
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA; Department of Surgery, Weill Cornell Medical College, New York, NY, 10065 USA; Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: jmb2009@med.cornell.edu.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Butler
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D066026:Endothelial Progenitor Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D006410:Hematopoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D055153:Stem Cell Niche; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation
chemical_list: D016207:Cytokines; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt