title: ECM-Dependence of Endothelial Progenitor Cell Features.
abstract: Preserving self-renewal, multipotent capacity, and large-scale expansion of highly functional progenitor cells, including endothelial progenitor cells (EPCs), is a controversial issue. These current limitations, therefore, raise the need of developing promising in vitro conditions for prolonged expansion of EPCs without loss of their stemness feature. In the current study, the possible role of three different natural extracellular substrates, including collagen, gelatin, and fibronectin, on multiple parameters of EPCs such as cell morphology, phenotype, clonogenic, and vasculogenic properties was scrutinized. Next, EPCs from GFP-positive mice were pre-expanded on each of these ECM substrates and then systemically transplanted into sublethaly irradiated mice to analyze the potency of these cells for marrow reconstitution. Our results revealed considerable promise for fibronectin for EPC expansion with maintenance of stemness characteristics, whereas gelatin and collagen matrices directed the cells toward a mature endothelial phenotype. Transplantation of EPCs pre-expanded on fibronectin resulted in widespread distribution and appropriate engraftment to various tissues with habitation in close association with the microvasculature. In addition, fibronectin pre-expanded cells were gradually enriched in the bone marrow after transplantation, resulting in marrow repopulation and hematologic recovery, leading to improved survival of recipient mice whereas gelatin- and collagen-expanded cells failed to reconstitute the bone marrow. This study demonstrated that, cell characteristics of in vitro expanded EPCs are determined by the subjacent matrix. Fibronectin-expanded EPCs are heralded as a source of great promise for bone marrow reconstitution and neo-angiogenesis in therapeutic bone marrow transplantation. J. Cell. Biochem. 117: 1934-1946, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran.
authors.forename: Vahid
authors.initials: V
authors.lastname: Siavashi
authors.affiliation: Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
authors.forename: Seyed Mahdi
authors.initials: SM
authors.lastname: Nassiri
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Rahbarghazi
authors.affiliation: Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
authors.forename: Rana
authors.initials: R
authors.lastname: Vafaei
authors.affiliation: Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran.
authors.forename: Reyhaneh
authors.initials: R
authors.lastname: Sariri
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D016026:Bone Marrow Transplantation; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic
chemical_list: D005353:Fibronectins
keywords: BONE MARROW; ENDOTHELIAL PROGENITOR CELL; EXTRACELLULAR MATRIX; RECONSTITUTION