title: Spontaneous Differentiation of Human Mesenchymal Stem Cells on Poly-Lactic-Co-Glycolic Acid Nano-Fiber Scaffold.
abstract: BACKGROUND
  Mesenchymal stem cells (MSCs) have immunosuppressive activity and can differentiate into bone and cartilage; and thus seem ideal for treatment of rheumatoid arthritis (RA). Here, we investigated the osteogenesis and chondrogenesis potentials of MSCs seeded onto nano-fiber scaffolds (NFs) in vitro and possible use for the repair of RA-affected joints.
  
  
  METHODS
  MSCs derived from healthy donors and patients with RA or osteoarthritis (OA) were seeded on poly-lactic-glycolic acid (PLGA) electrospun NFs and cultured in vitro.
  
  
  RESULTS
  Healthy donor-derived MSCs seeded onto NFs stained positive with von Kossa at Day 14 post-stimulation for osteoblast differentiation. Similarly, MSCs stained positive with Safranin O at Day 14 post-stimulation for chondrocyte differentiation. Surprisingly, even cultured without any stimulation, MSCs expressed RUNX2 and SOX9 (master regulators of bone and cartilage differentiation) at Day 7. Moreover, MSCs stained positive for osteocalcin, a bone marker, and simultaneously also with Safranin O at Day 14. On Day 28, the cell morphology changed from a spindle-like to an osteocyte-like appearance with processes, along with the expression of dentin matrix protein-1 (DMP-1) and matrix extracellular phosphoglycoprotein (MEPE), suggesting possible differentiation of MSCs into osteocytes. Calcification was observed on Day 56. Expression of osteoblast and chondrocyte differentiation markers was also noted in MSCs derived from RA or OA patients seeded on NFs. Lactic acid present in NFs potentially induced MSC differentiation into osteoblasts.
  
  
  CONCLUSIONS
  Our PLGA scaffold NFs induced MSC differentiation into bone and cartilage. NFs induction process resembled the procedure of endochondral ossification. This finding indicates that the combination of MSCs and NFs is a promising therapeutic technique for the repair of RA or OA joints affected by bone and cartilage destruction.
authors.affiliation: The First department of internal medicine, school of medicine, University of occupational and environmental health, Kitakyushu, Fukuoka, Japan.|Rheumatology, National hospital organization Beppu medical center, Beppu, Oita, Japan.
authors.forename: Koshiro
authors.initials: K
authors.lastname: Sonomoto
authors.affiliation: The First department of internal medicine, school of medicine, University of occupational and environmental health, Kitakyushu, Fukuoka, Japan.|Internal medicine, division of rheumatology, Keio university, Shinjuku-ku, Tokyo, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yamaoka
authors.affiliation: Integrative technology research institute, Teijin Limited, Hino, Tokyo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kaneko
authors.affiliation: The First department of internal medicine, school of medicine, University of occupational and environmental health, Kitakyushu, Fukuoka, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Yamagata
authors.affiliation: The First department of internal medicine, school of medicine, University of occupational and environmental health, Kitakyushu, Fukuoka, Japan.|Research unit B, research division, Mitsubishi Tanabe pharma corporation, Yokohama, Kanagawa, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Sakata
authors.affiliation: The First department of internal medicine, school of medicine, University of occupational and environmental health, Kitakyushu, Fukuoka, Japan.
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The First department of internal medicine, school of medicine, University of occupational and environmental health, Kitakyushu, Fukuoka, Japan.|Research unit B, research division, Mitsubishi Tanabe pharma corporation, Yokohama, Kanagawa, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kondo
authors.affiliation: Department of orthopedics, school of medicine, University of occupational and environmental health, Kitakyushu, Fukuoka, Japan.
authors.forename: Yukichi
authors.initials: Y
authors.lastname: Zenke
authors.affiliation: Department of orthopedics, school of medicine, University of occupational and environmental health, Kitakyushu, Fukuoka, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Sabanai
authors.affiliation: The First department of internal medicine, school of medicine, University of occupational and environmental health, Kitakyushu, Fukuoka, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakayamada
authors.affiliation: Department of orthopedics, school of medicine, University of occupational and environmental health, Kitakyushu, Fukuoka, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Sakai
authors.affiliation: The First department of internal medicine, school of medicine, University of occupational and environmental health, Kitakyushu, Fukuoka, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001672:Biocompatible Materials / Q000737:chemistry; D015153:Blotting, Western; D016022:Case-Control Studies; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D020219:Chondrogenesis / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D057139:Nanofibers / Q000737:chemistry*; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000502:physiology*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D012333:RNA, Messenger; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid