title: Therapeutic superiority for cartilage repair by CD271-positive marrow stromal cell transplantation.
abstract: Recent reports indicated that human isolated CD271+ bone marrow mesenchymal stromal cells (BM-MSCs) have a greater expansion and potential for multipotent differentiation including chondrogenesis than classical plastic adherent (PA) BM-MSCs in vitro. Therefore, we set up a hypothesis that CD271+ MSCs may have a greater chondrogenic potential than PA-MSCs in vitro and in vivo. We investigated the superiority of CD271+ MSCs on chondrogenesis using in vitro expansion and pellet culture system and in vivo rat model of cartilage defect when compared to PA-MSCs. In the in vitro study, CD271+ MSCs showed higher expansion potential and produced larger pellets with higher expressions of chondrogenic genes when compared to the control groups. During the culture, CD271 expression decreased, which resulted in decreased chondrogenesis. In the in vivo study, immunohistochemical staining demonstrated differentiated human chondrocytes identified as double-stained cells with human-specific collagen type 2 and human leukocyte antigen-ABC in CD271+ and PA groups. The number of double-stained cells was significantly higher in the CD271+ group than PA group. Real-time RT-PCR analysis of tissue RNA isolated from the chondral defect site for human-specific chondrogenic markers demonstrated a significantly higher expression in CD271+ group than PA group. Macroscopic examination of chondral defect sites at week 8 revealed glossy white and well-integrated repaired tissues in the CD271+ and PA groups, but not in the PBS group. The average histological score in the CD271+ group was significantly greater than in the other groups. Apoptosis analysis at the cell transplanted site with TUNEL staining showed that the CD271+ group had significantly fewer apoptotic chondrocytes compared with the PA group. These results indicate that CD271+ MSCs have a greater chondrogenic potential than PA-MSCs in both in vitro and in vivo conditions.
authors.affiliation: Stem Cell Translational Research, Kobe Institute of Biomedical Research and Innovation, Kobe, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Mifune
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Murasawa
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Kawamoto
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kuroda
authors.forename: Taro
authors.initials: T
authors.lastname: Shoji
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kuroda
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Fukui
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosaka
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asahara
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology*; D002357:Cartilage Diseases / Q000378:metabolism / Q000628:therapy*; D002454:Cell Differentiation; D020219:Chondrogenesis; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010641:Phenotype; D051381:Rats; D011923:Rats, Nude; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D024043:Collagen Type II; D006680:HLA Antigens; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; D055758:SOX9 Transcription Factor