title: Immortalized multipotent pericytes derived from the vasa vasorum in the injured vasculature. A cellular tool for studies of vascular remodeling and regeneration.
abstract: Adventitial microvessels, vasa vasorum in the vessel walls, have an active role in the vascular remodeling, although its mechanisms are still unclear. It has been reported that microvascular pericytes (PCs) possess mesenchymal plasticity. Therefore, microvessels would serve as a systemic reservoir of stem cells and contribute to the tissues remodeling. However, most aspects of the biology of multipotent PCs (mPCs), in particular of pathological microvessels are still obscure because of the lack of appropriate methods to detect and isolate these cells. In order to examine the characteristics of mPCs, we established immortalized cells residing in adventitial capillary growing at the injured vascular walls. We recently developed in vivo angiogenesis to observe adventitial microvessels using collagen-coated tube (CCT), which also can be used as an adventitial microvessel-rich tissue. By using the CCT, CD146- or NG2-positive cells were isolated from the adventitial microvessels in the injured arteries of mice harboring a temperature-sensitive SV40 T-antigen gene. Several capillary-derived endothelial cells (cECs) and PCs (cPCs) cell lines were established. cECs and cPCs maintain a number of key endothelial and PC features. Co-incubation of cPCs with cECs formed capillary-like structure in Matrigel. Three out of six cPC lines, termed capillary mPCs demonstrated both mesenchymal stem cell- and neuronal stem cell-like phenotypes, differentiating effectively into adipocytes, osteoblasts, as well as schwann cells. mPCs differentiated to ECs and PCs, and formed capillary-like structure on their own. Transplanted DsRed-expressing mPCs were resident in the capillary and muscle fibers and promoted angiogenesis and myogenesis in damaged skeletal muscle. Adventitial mPCs possess transdifferentiation potential with unique phenotypes, including the reconstitution of capillary-like structures. Their phenotype would contribute to the pathological angiogenesis associated with vascular remodeling. These cell lines also provide a reproducible cellular tool for high-throughput studies on angiogenesis, vascular remodeling, and regeneration as well.
authors.affiliation: Division of Cardiovascular, Respiratory and Neurology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Kabara
authors.affiliation: Department of Cardiovascular Regeneration and Innovation, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kawabe
authors.affiliation: Division of Cardiovascular, Respiratory and Neurology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Matsuki
authors.affiliation: Department of Anatomy, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hira
authors.affiliation: Division of Cardiovascular, Respiratory and Neurology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Akiho
authors.initials: A
authors.lastname: Minoshima
authors.affiliation: Division of Cardiovascular, Respiratory and Neurology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Shimamura
authors.affiliation: Division of Cardiovascular, Respiratory and Neurology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamauchi
authors.affiliation: Division of Cardiovascular, Respiratory and Neurology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Aonuma
authors.affiliation: Division of Cardiovascular, Respiratory and Neurology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nishimura
authors.affiliation: Department of Vascular Surgery, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Cardiovascular Regeneration and Innovation, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Naofumi
authors.initials: N
authors.lastname: Takehara
authors.affiliation: 1] Division of Cardiovascular, Respiratory and Neurology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan [2] Department of Cardiovascular Regeneration and Innovation, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Hasebe
mesh_terms: D000818:Animals; D000941:Antigens; D002196:Capillaries / Q000473:pathology*; D002454:Cell Differentiation; D002469:Cell Separation; D042783:Endothelial Cells / Q000502:physiology; D051379:Mice; D016513:Mice, SCID; D018919:Neovascularization, Physiologic; D020286:Pericytes / Q000502:physiology*; D011509:Proteoglycans; D012038:Regeneration / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology; D059467:Transcriptome; D014651:Vasa Vasorum / Q000166:cytology*; D066253:Vascular Remodeling; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4