title: Proangiogenic features of Wharton's jelly-derived mesenchymal stromal/stem cells and their ability to form functional vessels.
abstract: Mesenchymal stromal/stem cells derived from human Wharton's jelly (WJ-MSC) have emerged as a favorable source for autologous and allogenic cell therapy. Here, we characterized the proangiogenic features of WJ-MSCs and examined their ability to form functional vessels in in vivo models. First, we examined whether WJ-MSCs express endothelial and smooth muscle cell specific markers after culture in endothelial growth media. WJ-MSCs expressed an endothelial specific marker, VEGFR1, at mRNA and protein levels, but did not express other specific markers (VEGFR2, Tie2, vWF, CD31, and VE-cadherin). Rather, WJ-MSCs expressed smooth muscle cell specific markers, α-SMA, PDGFR-β and calponin, and were unable to form tube-like structures with lumen on Matrigel. WJ-MSCs secreted growth factors including angiogenin, IGFBP-3, MCP-1, and IL-8, which stimulated endothelial proliferation, migration, and tube formation. When WJ-MSCs suspended in Matrigel were implanted into nude mice, it led to formation of functional vessels containing erythrocytes after 7 days. However, implantation of endothelial cell-suspended Matrigel resulted in no perfused vessels. The implanted WJ-MSCs were stained positively for calponin or PDGFR-β and were located adjacent to the lining of mouse endothelial cells that were stained with labeled BS-lectin B4. In a murine hindlimb ischemia model, the transplantation of MSCs (5×10(5)cells) into the ischemic limbs improved perfusion recovery and neovascularization of the limbs compared to control group. Therefore, the results suggest that WJ-MSCs promote neovascularization and perfusion by secreting paracrine factors and by functioning as perivascular precursor cells, and that WJ-MSCs can be used efficiently for cell therapy of ischemic disease.
authors.affiliation: Cancer Research Institute and Department of Medical Lifescience, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Moran
authors.initials: M
authors.lastname: Choi
authors.forename: Hyun-Sun
authors.initials: HS
authors.lastname: Lee
authors.forename: Purevjargal
authors.initials: P
authors.lastname: Naidansaren
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Kim
authors.forename: Eunju
authors.initials: E
authors.lastname: O
authors.forename: Jung-Ho
authors.initials: JH
authors.lastname: Cha
authors.forename: Hyun-Young
authors.initials: HY
authors.lastname: Ahn
authors.forename: Park In
authors.initials: PI
authors.lastname: Yang
authors.forename: Jong-Chul
authors.initials: JC
authors.lastname: Shin
authors.forename: Young Ae
authors.initials: YA
authors.lastname: Joe
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001808:Blood Vessels / Q000166:cytology / Q000254:growth & development*; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology; D005121:Extremities / Q000473:pathology / Q000637:transplantation; D020869:Gene Expression Profiling; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008819:Mice, Nude; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D018919:Neovascularization, Physiologic
chemical_list: D015415:Biomarkers