title: Fate of bone marrow mesenchymal stromal cells following autologous transplantation in a rabbit model of osteonecrosis.
abstract: OBJECTIVE
  Internalizing quantum dots (i-QDs) are a useful tool for tracking cells in vivo in models of tissue regeneration. We previously synthesized i-QDs by conjugating QDs with a unique internalizing antibody against a heat shock protein 70 family stress chaperone. In the present study, i-QDs were used to label rabbit mesenchymal stromal cells (MSCs) that were then transplanted into rabbits to assess differentiation potential in an osteonecrosis model.
  
  
  METHODS
  The i-QDs were taken up by bone marrow-derived MSCs collected from the iliac of 12-week-old Japanese white rabbits that were positive for cluster of differentiation (CD)81 and negative for CD34 and human leukocyte antigen DR. The average rate of i-QD internalization was 93.3%. At 4, 8, 12, and 24 weeks after transplantation, tissue repair was evaluated histologically and by epifluorescence and electron microscopy.
  
  
  RESULTS
  The i-QDs were detected at the margins of the drill holes and in the necrotized bone trabecular. There was significant colocalization of the i-QD signal in transplanted cells and markers of osteoblast and mineralization at 4, 8, and 12 weeks post-transplantation, while i-QDs were detected in areas of mineralization at 12 and 24 weeks post-transplantation. Moreover, i-QDs were observed in osteoblasts in regenerated tissue by electron microscopy, demonstrating that the tissue was derived from transplanted cells.
  
  
  CONCLUSIONS
  These results indicate that transplanted MSCs can differentiate into osteoblasts and induce tissue repair in an osteonecrosis model and can be tracked over the long term by i-QD labeling.
authors.affiliation: Department of Orthopaedic Surgery, University of Tsukuba, Ibaraki, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sugaya
authors.affiliation: Department of Orthopaedic Surgery, University of Tsukuba, Ibaraki, Japan. Electronic address: hmishima@md.tsukuba.ac.jp.
authors.forename: Hajime
authors.initials: H
authors.lastname: Mishima
authors.affiliation: National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan.
authors.forename: Ran
authors.initials: R
authors.lastname: Gao
authors.affiliation: National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan.
authors.forename: Sunil C
authors.initials: SC
authors.lastname: Kaul
authors.affiliation: National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan.
authors.forename: Renu
authors.initials: R
authors.lastname: Wadhwa
authors.affiliation: Department of Orthopaedic Surgery, University of Tsukuba, Ibaraki, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Aoto
authors.affiliation: Department of Orthopaedic Surgery, University of Tsukuba, Ibaraki, Japan.
authors.forename: Meihua
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, University of Tsukuba, Ibaraki, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Yoshioka
authors.affiliation: Department of Orthopaedic Surgery, University of Tsukuba, Ibaraki, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ogawa
authors.affiliation: Department of Orthopaedic Surgery, University of Tsukuba, Ibaraki, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Ochiai
authors.affiliation: Department of Orthopaedic Surgery, University of Tsukuba, Ibaraki, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Yamazaki
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001853:Bone Marrow; D001854:Bone Marrow Cells / Q000166:cytology; D001842:Bone and Bones / Q000166:cytology; D002454:Cell Differentiation / Q000502:physiology; D058948:Cell Tracking / Q000379:methods*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010006:Osteoblasts / Q000166:cytology*; D010020:Osteonecrosis / Q000628:therapy*; D045663:Quantum Dots / Q000378:metabolism*; D011817:Rabbits; D060225:Tetraspanin 28 / Q000378:metabolism; D014182:Transplantation, Autologous
chemical_list: D018952:Antigens, CD34; D060225:Tetraspanin 28
keywords: bone marrow-derived mesenchymal stromal cells; cell tracking; conjugation; internalizing anti-mortalin antibody; quantum dots; transplantation