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Cultured and expanded CD34+ cells aid fracture healing in rats



DOI:10.1038/bonekey.2012.235

Kawakami et al. report a new method of cell expansion for CD34+ cells, enabling them to be harvested in sufficient quantities to test their ability to enhance neovascularization and fracture healing.

The expansion method consisted of culturing CD34+ cells derived from bone marrow with a mixed medium containing vascular endothelial growth factor, interleukin-6, stem cell factor, thrombopoietin and Fms-related tyrosin kinase-3 for 7 days. This increased the yield 20-fold, and the resulting cells showed significantly higher proliferation activity compared to the equivalent cells used fresh.

The cultured cells were then also compared with fresh cells for their ability to enhance radiographic fracture healing in a rat model. Cultured and expanded CD34+ cells were significantly more potent than fresh cells (bridging callus formation in 9/10 compared to 2/10 fractures) and were also more successful than high-dose fresh cells (7/10 fractures showed callus formation). There was no callus formation in rats treated with control phosphate buffered saline (PBS).

Editor’s comment: This study in a nude rat model shows that non-union fractures (elicited by intra-operative periosteal cauterisation) could be healed by both expanded and non-expanded human CD34 cells from bone marrow. A fairly clear dose response was observed, with expanded>non-expanded high dose>non-expanded low dose>PBS. This thorough experiment underscores the potential for translation of this strategy, but further experiments in larger animals are now required.


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