Stem cell therapy: is there a future for reconstruction of large bone defects?

Large bone defects caused by fracture, non-union and bone tumor excision has been a major clinical problem. Autogenous bone grafting and Ilizarov method are commonly performed to treat them. However, bone grafting has limitation in volume of available bone, and Ilizarov method requires long periods of time to treat. Accordingly, there is need for stem cell therapy for bone repair and/or regeneration. Mesenchymal stem cells (MSCs) hold the ability to differentiate into osteoblasts and are available from a wide variety of sources. The route of "intramembranous ossification (direct bone formation)" by transplantation of undifferentiated MSCs has been tested but it did not demonstrate the success initially envisaged. Recently another approach has been examined being the transplantation of "MSCs pre-differentiated in vitro into cartilage-forming chondrocytes" into bone defect, in brief, representing the route of "endochondral ossification (indirect bone formation)". It's a paradigm shift of Stem Cell Therapy for bone regeneration. We have already reported on the healing of large femur defects in rats by transplantation of "MSCs pre-differentiated in vitro into cartilage-forming chondrocytes". We named the cells as Mesenchymal Stem Cell-Derived Chondrocytes (MSC-DCs). The success of reconstruction of a massive 15-mm femur defect (approximately 50% of the rat femur shaft length) provides a sound foundation for potential clinical application of this technique. We believe our results may offer a new avenue of reconstruction of large bone defect, especially in view of the their high reproducibility and the excellent biomechanical strength of repaired femora.