Locally applied osteogenic predifferentiated progenitor cells are more effective than undifferentiated mesenchymal stem cells in the treatment of delayed bone healing.

Mesenchymal stem cells (MSCs) and osteogenic predifferentiated cells (OPCs) have been shown to promote healing of critical-sized bone defects. This study investigated the regenerative capacity of autologous MSCs versus OPCs after local injection into a compromised bone healing situation. We hypothesized that treatment with MSCs and OPCs would enhance the healing and that the MSCs would be more effective due to their lower differentiation and higher proliferative competence. The femur of rats was osteotomized and stabilized with an external fixator. Except for the control group (C group), in all animals a delayed healing was induced by cautering the periosteum and removing the bone marrow. Two days postsurgery, autologous MSCs (MSC group), OPCs (OPC group), or cell-free medium (Sham group) was percutaneously injected into the osteotomy gap. The C group received no treatment. Bone healing was evaluated radiologically, biomechanically, and histologically. After 8 weeks, the C group showed complete bony bridging, while a delayed healing was detected in the Sham group. All outcome measures showed better healing of the OPC group compared to the Sham group. Contrary to our expectations, there were no significant differences in outcome measures between the MSC group and the Sham group. The percutaneous injection of OPCs could become a minimally invasive treatment option for delayed or nonunions.