title: Allogeneic injection of fetal membrane-derived mesenchymal stem cells induces therapeutic angiogenesis in a rat model of hind limb ischemia.
abstract: Bone marrow-derived mesenchymal stem cells (BM-MSC) have been demonstrated to be an attractive therapeutic cell source for tissue regeneration and repair. However, it remains unknown whether or not allogeneic transplantation of mesenchymal stem cells (MSC) derived from fetal membranes (FM), which are generally discarded as medical waste after delivery, has therapeutic potential. FM-MSC were obtained from Lewis rats and had surface antigen expression and multipotent potential partly similar to those of BM-MSC. Compared with BM-MSC, FM-MSC secreted a comparable amount of hepatocyte growth factor despite a small amount of vascular endothelial growth factor. FM-MSC and BM-MSC both expressed major histocompatibility complex (MHC) class I but not MHC class II antigens and did not elicit allogeneic lymphocyte proliferation in mixed lymphocyte culture. FM-MSC or BM-MSC obtained from Lewis rats were injected into a MHC-mismatched August-Copenhagen-Irish rat model of hind limb ischemia. Three weeks after injection, blood perfusion and capillary density were significantly higher in the FM-MSC and BM-MSC groups than in the phosphate-buffered saline group, and allogeneic FM-MSC and BM-MSC were still observed. In nonischemic hind limb tissues, allogeneic FM-MSC and BM-MSC injection were associated with a comparatively small amount of T lymphocyte infiltration, compared with the injection of allogeneic splenic lymphocytes. In conclusion, allogeneic FM-MSC injection did not elicit a lymphocyte proliferative response and provided significant improvement in a rat model of hind limb ischemia, comparable to the response to BM-MSC. Thus, allogeneic injection of FM-MSC may be a new therapeutic strategy for the treatment of severe peripheral vascular disease. Disclosure of potential conflicts of interest is found at the end of this article.
authors.affiliation: Department of Perinatology, National Cardiovascular Center Research Institute, Suita, Osaka, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Ishikane
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ohnishi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yamahara
authors.forename: Masaharu
authors.initials: M
authors.lastname: Sada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Harada
authors.forename: Kenichi
authors.initials: K
authors.lastname: Mishima
authors.forename: Katsunori
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Michihiro
authors.initials: M
authors.lastname: Fujiwara
authors.forename: Soichiro
authors.initials: S
authors.lastname: Kitamura
authors.forename: Noritoshi
authors.initials: N
authors.lastname: Nagaya
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ikeda
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005321:Extraembryonic Membranes / Q000166:cytology*; D006614:Hindlimb / Q000098:blood supply* / Q000473:pathology*; D007267:Injections; D007511:Ischemia / Q000628:therapy*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009132:Muscles / Q000166:cytology / Q000276:immunology; D018919:Neovascularization, Physiologic; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000166:cytology; D014184:Transplantation, Homologous
chemical_list: D043925:Angiogenesis Inducing Agents