title: Therapeutic Potential of Adipose-Derived SSEA-3-Positive Muse Cells for Treating Diabetic Skin Ulcers.
abstract: Stage-specific embryonic antigen-3 (SSEA-3)-positive multipotent mesenchymal cells (multilineage differentiating stress-enduring [Muse] cells) were isolated from cultured human adipose tissue-derived stem/stromal cells (hASCs) and characterized, and their therapeutic potential for treating diabetic skin ulcers was evaluated. Cultured hASCs were separated using magnetic-activated cell sorting into positive and negative fractions, a SSEA-3+ cell-enriched fraction (Muse-rich) and the remaining fraction (Muse-poor). Muse-rich hASCs showed upregulated and downregulated pluripotency and cell proliferation genes, respectively, compared with Muse-poor hASCs. These cells also released higher amounts of certain growth factors, particularly under hypoxic conditions, compared with Muse-poor cells. Skin ulcers were generated in severe combined immunodeficiency (SCID) mice with type 1 diabetes, which showed delayed wound healing compared with nondiabetic SCID mice. Treatment with Muse-rich cells significantly accelerated wound healing compared with treatment with Muse-poor cells. Transplanted cells were integrated into the regenerated dermis as vascular endothelial cells and other cells. However, they were not detected in the surrounding intact regions. Thus, the selected population of ASCs has greater therapeutic effects to accelerate impaired wound healing associated with type 1 diabetes. These cells can be achieved in large amounts with minimal morbidity and could be a practical tool for a variety of stem cell-depleted or ischemic conditions of various organs and tissues.
authors.affiliation: Department of Plastic Surgery, University of Tokyo Graduate School of Medicine, Tokyo, Japan; Research Center for Stem Cell Engineering, National Institute for Advanced Industrial Science and Technology, Ibaraki, Japan.
authors.forename: Kahori
authors.initials: K
authors.lastname: Kinoshita
authors.affiliation: Department of Plastic Surgery, University of Tokyo Graduate School of Medicine, Tokyo, Japan; Research Center for Stem Cell Engineering, National Institute for Advanced Industrial Science and Technology, Ibaraki, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Kuno
authors.affiliation: Department of Plastic Surgery, University of Tokyo Graduate School of Medicine, Tokyo, Japan; Research Center for Stem Cell Engineering, National Institute for Advanced Industrial Science and Technology, Ibaraki, Japan.
authors.forename: Hisako
authors.initials: H
authors.lastname: Ishimine
authors.affiliation: Department of Plastic Surgery, University of Tokyo Graduate School of Medicine, Tokyo, Japan; Research Center for Stem Cell Engineering, National Institute for Advanced Industrial Science and Technology, Ibaraki, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Aoi
authors.affiliation: Department of Plastic Surgery, University of Tokyo Graduate School of Medicine, Tokyo, Japan; Research Center for Stem Cell Engineering, National Institute for Advanced Industrial Science and Technology, Ibaraki, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Mineda
authors.affiliation: Department of Plastic Surgery, University of Tokyo Graduate School of Medicine, Tokyo, Japan; Research Center for Stem Cell Engineering, National Institute for Advanced Industrial Science and Technology, Ibaraki, Japan.
authors.forename: Harunosuke
authors.initials: H
authors.lastname: Kato
authors.affiliation: Department of Plastic Surgery, University of Tokyo Graduate School of Medicine, Tokyo, Japan; Research Center for Stem Cell Engineering, National Institute for Advanced Industrial Science and Technology, Ibaraki, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Doi
authors.affiliation: Department of Plastic Surgery, University of Tokyo Graduate School of Medicine, Tokyo, Japan; Research Center for Stem Cell Engineering, National Institute for Advanced Industrial Science and Technology, Ibaraki, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kanayama
authors.affiliation: Department of Plastic Surgery, University of Tokyo Graduate School of Medicine, Tokyo, Japan; Research Center for Stem Cell Engineering, National Institute for Advanced Industrial Science and Technology, Ibaraki, Japan.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Plastic Surgery, University of Tokyo Graduate School of Medicine, Tokyo, Japan; Research Center for Stem Cell Engineering, National Institute for Advanced Industrial Science and Technology, Ibaraki, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Mashiko
authors.affiliation: Department of Plastic Surgery, University of Tokyo Graduate School of Medicine, Tokyo, Japan; Research Center for Stem Cell Engineering, National Institute for Advanced Industrial Science and Technology, Ibaraki, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kurisaki
authors.affiliation: Department of Plastic Surgery, University of Tokyo Graduate School of Medicine, Tokyo, Japan; Research Center for Stem Cell Engineering, National Institute for Advanced Industrial Science and Technology, Ibaraki, Japan kotaro-yoshimura@umin.ac.jp.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Yoshimura
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000096:biosynthesis*; D048909:Diabetes Complications / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D005260:Female; D064593:Heterografts; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D016513:Mice, SCID; D039902:Multipotent Stem Cells / Q000378:metabolism*; D012883:Skin Ulcer / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D055746:Stage-Specific Embryonic Antigens / Q000096:biosynthesis*; D014945:Wound Healing
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D055746:Stage-Specific Embryonic Antigens; C052924:stage-specific embryonic antigen-3
keywords: Adipose; Adult stem cells; Cell culture; Endothelial cell; Hyaluronan; Mesenchymal stem cells; Stem cell transplantation; Tissue regeneration