title: Fate of bone marrow mesenchymal stem cells following the allogeneic transplantation of cartilaginous aggregates into osteochondral defects of rabbits.
abstract: The purpose of this study was to track mesenchymal stem cells (MSCs) labelled with internalizing quantum dots (i-QDs) in the reparative tissues, following the allogeneic transplantation of three-dimensional (3D) cartilaginous aggregates into the osteochondral defects of rabbits. QDs were conjugated with a unique internalizing antibody against a heat shock protein-70 (hsp70) family stress chaperone, mortalin, which is upregulated and expressed on the surface of dividing cells. The i-QDs were added to the culture medium for 24 h. Scaffold-free cartilaginous aggregates formed from i-QD-labelled MSCs (i-MSCs), using a 3D culture system with chondrogenic supplements for 1 week, were transplanted into osteochondral defects of rabbits. At 4, 8 and 26 weeks after the transplantation, the reparative tissues were evaluated macroscopically, histologically and fluoroscopically. At as early as 4 weeks, the defects were covered with a white tissue resembling articular cartilage. In histological appearance, the reparative tissues resembled hyaline cartilage on safranin-O staining throughout the 26 weeks. In the deeper portion, subchondral bone and bone marrow were well remodelled. On fluoroscopic evaluation, QDs were tracked mainly in bone marrow stromata, with some signals detected in cartilage and the subchondral bone layer. We showed that the labelling of rabbit MSCs with anti-mortalin antibody-conjugated i-QDs is a tolerable procedure and provides a stable fluorescence signal during the cartilage repair process for up to 26 weeks after transplantation. The results suggest that i-MSCs did not inhibit, and indeed contributed to, the regeneration of osteochondral defects.
authors.affiliation: Department of Orthopaedic Surgery, University of Tsukuba, Ibaraki, Japan. tymd99@gmail.com
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Hajime
authors.initials: H
authors.lastname: Mishima
authors.forename: Zeenia
authors.initials: Z
authors.lastname: Kaul
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Ohyabu
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Sakai
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Ochiai
authors.forename: Sunil C
authors.initials: SC
authors.lastname: Kaul
authors.forename: Renu
authors.initials: R
authors.lastname: Wadhwa
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Uemura
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology*; D002358:Cartilage, Articular / Q000166:cytology*; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D045663:Quantum Dots; D011817:Rabbits; D014184:Transplantation, Homologous