title: The role of CCL5 in the ability of adipose tissue-derived mesenchymal stem cells to support repair of ischemic regions.
abstract: Mesenchymal stem cells (MSC) are multipotent and possess high proliferative activity, and thus are thought to be a reliable cell source for cell therapies. Here, we isolated MSC from adult tissues--bone marrow (BM-MSC), dental tissue (DT-MSC), and adipose tissue (AT-MSC)--to compare how autotransplantation of these MSC effectively supports the repair of bone fracture and ischemic tissue. An analysis by in vitro differentiation assays showed no significant difference among these MSC. The degree of calcification at the joint region of bone fracture was higher in mice transplanted with AT-MSC than in mice transplanted with BM-MSC or DT-MSC. To compare the abilities of MSC, characterize how those MSC affect the repair of ischemic tissue, vascular occlusion was performed by ligation of the femoral artery and vein. Of note, the blood flow in the ischemic region rapidly increased in mice injected with AT-MSC, as contrasted with mice injected with BM- or DT-MSC. The number of CD45- and F4/80-positive cells at the femoral region was higher in AT-MSC recipients than in recipients of BM-MSC or DT-MSC. We evaluated the mRNA expression of angiogenic and migration factors in MSC and found the expression of CCL5 mRNA was higher in AT-MSC than in BM-MSC or DT-MSC. Transplantation of AT-MSC with impaired expression of CCL5 clearly showed a significant delay in the recovery of blood flow compared with the control. These findings have fundamental implications for the modulation of AT-MSC in the repair of vasculature and bone fracture.
authors.affiliation: 1 Department of Regenerative Medicine and Stem Cell Biology, Graduate School of Comprehensive Human Sciences, University of Tsukuba , Tsukuba, Japan .
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kimura
authors.forename: Masumi
authors.initials: M
authors.lastname: Nagano
authors.forename: Georgina
authors.initials: G
authors.lastname: Salazar
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yamashita
authors.forename: Ikki
authors.initials: I
authors.lastname: Tsuboi
authors.forename: Hajime
authors.initials: H
authors.lastname: Mishima
authors.forename: Shonosuke
authors.initials: S
authors.lastname: Matsushita
authors.forename: Fujio
authors.initials: F
authors.lastname: Sato
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamagata
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohneda
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy; D018946:Chemokine CCL5 / Q000096:biosynthesis* / Q000235:genetics; D050723:Fractures, Bone / Q000628:therapy; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007511:Ischemia / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D012333:RNA, Messenger