title: Equal modulation of endothelial cell function by four distinct tissue-specific mesenchymal stem cells.
abstract: Mesenchymal stem cells (MSCs) can generate multiple end-stage mesenchymal cell types and constitute a promising population of cells for regenerative therapies. Additionally, there is increasing evidence supporting other trophic activities of MSCs, including the ability to enable formation of vasculature in vivo. Although MSCs were originally isolated from the bone marrow, the presence of these cells in the stromal vascular fraction of multiple adult tissues has been recently recognized. However, it is unknown whether the capacity to modulate vasculogenesis is ubiquitous to all MSCs regardless of their tissue of origin. Here, we demonstrated that tissue-resident MSCs isolated from four distinct tissues have equal capacity to modulate endothelial cell function, including formation of vascular networks in vivo. MSCs were isolated from four murine tissues, including bone marrow, white adipose tissue, skeletal muscle, and myocardium. In culture, all four MSC populations secreted a plethora of pro-angiogenic factors that unequivocally induced proliferation, migration, and tube formation of endothelial colony-forming cells (ECFCs). In vivo, co-implantation of MSCs with ECFCs into mice generated an extensive network of blood vessels with ECFCs specifically lining the lumens and MSCs occupying perivascular positions. Importantly, there were no differences among all four MSCs evaluated. Our studies suggest that the capacity to modulate the formation of vasculature is a ubiquitous property of all MSCs, irrespective of their original anatomical location. These results validate multiple tissues as potential sources of MSCs for future cell-based vascular therapies.
authors.affiliation: Department of Cardiac Surgery, Children's Hospital Boston, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, USA.
authors.forename: Ruei-Zeng
authors.initials: RZ
authors.lastname: Lin
authors.forename: Rafael
authors.initials: R
authors.lastname: Moreno-Luna
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.forename: William T
authors.initials: WT
authors.lastname: Pu
authors.forename: Juan M
authors.initials: JM
authors.lastname: Melero-Martin
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic