title: Placenta Mesenchymal Stem Cell Derived Exosomes Confer Plasticity on Fibroblasts.
abstract: Mesenchymal stem cell (MSC)-conditioned medium (MSC-CM) has been reported to enhance wound healing. Exosomes contain nucleic acids, proteins, and lipids, and function as an intercellular communication vehicle for mediating some paracrine effects. However, the function of MSC-derived exosomes (MSC-exo) remains elusive. In this study, we isolated human placenta MSC (PlaMSC)-derived exosomes (PlaMSC-exo) and examined their function in vitro. PlaMSCs were isolated from human term placenta using enzymatic digestion. PlaMSC-exo were prepared from the conditioned medium of PlaMSC (PlaMSC-CM) by ultracentrifugation. The expression of stemness-related genes, such as OCT4 and NANOG, in normal adult human dermal fibroblasts (NHDF) after incubation with PlaMSC-exo was measured by real-time reverse transcriptase PCR analysis (real-time PCR). The effect of PlaMSC-exo on OCT4 transcription activity was assessed using Oct4-EGFP reporter mice-derived dermal fibroblasts. The stimulating effects of PlaMSC-exo on osteoblastic and adipocyte-differentiation of NHDF were evaluated by alkaline phosphatase (ALP), and Alizarin red S- and oil red O-staining, respectively. The expression of osteoblast- and adipocyte-related genes was also assessed by real-time PCR. The treatment of NHDF with PlaMSC-exo significantly upregulated OCT4 and NANOG mRNA expression. PlaMSC-exo also enhanced OCT4 transcription. The NHDF treated with PlaMSC-exo exhibited osteoblastic and adipocyte-differentiation in osteogenic and adipogenic induction media. PlaMSC-exo increase the expression of OCT4 and NANOG mRNA in fibroblasts. As a result, PlaMSC-exo influence the differentiation competence of fibroblasts to both osteoblastic and adipocyte-differentiation. It shows a new feature of MSCs and the possibility of clinical application of MSC-exo. J. Cell. Biochem. 117: 1658-1670, 2016. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Periodontology, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tooi
authors.affiliation: Department of Nanomedicine (DNP), Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Komaki
authors.affiliation: Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Morioka
authors.affiliation: Department of Comprehensive Reproductive Medicine, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Honda
authors.affiliation: Department of Nanomedicine (DNP), Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Iwasaki
authors.affiliation: Life Science Laboratory, Research and Development Center, Dai Nippon Printing Co., Ltd., 1-1-1 Kaga-cho, Shinjuku-ku, Tokyo, 162-8001, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yokoyama
authors.affiliation: Life Science Laboratory, Research and Development Center, Dai Nippon Printing Co., Ltd., 1-1-1 Kaga-cho, Shinjuku-ku, Tokyo, 162-8001, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Ayame
authors.affiliation: Department of Periodontology, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Izumi
authors.affiliation: Department of Cellular Physiological Chemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Morita
mesh_terms: D055354:Exosomes / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D000071317:Nanog Homeobox Protein / Q000096:biosynthesis*; D050814:Octamer Transcription Factor-3 / Q000097:blood*; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy
chemical_list: C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human
keywords: DIFFERENTIATION; EXOSOMES; MESENCHYMAL STEM CELLS; NANOG; OCT4; PLACENTA; PLASTICITY