Fate of bone marrow mesenchymal stromal cells following autologous transplantation in a rabbit model of osteonecrosis

Cytotherapy. 2016 Feb;18(2):198-204. doi: 10.1016/j.jcyt.2015.10.016.

Abstract

Background aims: 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.

Conclusion: 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.

Keywords: bone marrow-derived mesenchymal stromal cells; cell tracking; conjugation; internalizing anti-mortalin antibody; quantum dots; transplantation.

MeSH terms

  • Animals
  • Antigens, CD34 / metabolism
  • Bone Marrow
  • Bone Marrow Cells / cytology
  • Bone and Bones / cytology
  • Cell Differentiation / physiology
  • Cell Tracking / methods*
  • Humans
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / cytology*
  • Osteoblasts / cytology*
  • Osteonecrosis / therapy*
  • Quantum Dots / metabolism*
  • Rabbits
  • Tetraspanin 28 / metabolism
  • Transplantation, Autologous

Substances

  • Antigens, CD34
  • Tetraspanin 28