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

• Internalizing quantum dots (i-QDs) were taken up by mesenchymal stromal cells (MSCs).
• MSCs transplanted into osteonecrotic rabbits differentiated into osteoblasts.
• I-QDs were present in the cytoplasm of osteoblasts in the repaired tissue.
• Transplanted MSCs can induce repair of osteonecrotic tissue and be tracked by i-QDs.

Background aimsInternalizing 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.MethodsThe 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.ResultsThe 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.ConclusionThese 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.

Graphical AbstractFate of bone marrow mesenchymal stromal cells following autologous transplantation in a rabbit model of osteonecrosisHisashi Sugaya, Hajime Mishima*, Ran Gao, Sunil C. Kaul, Renu Wadhwa, Katsuya Aoto, Meihua Li, Tomokazu Yoshioka, Takeshi Ogawa, Naoyuki Ochiai, Masashi YamazakiFigure optionsDownload as PowerPoint slide