Mesenchymal stem/stromal cells (MSC) are typically used to generate bone tissue by a process resembling intramembranous ossification, i.e., by direct osteoblastic differentiation. However, most bones develop by endochondral ossification, i.e., via remodeling of hypertrophic cartilaginous templates. To date, endochondral bone formation has not been reproduced using human, clinically compliant cell sources. Here, we aimed at engineering tissues from bone marrow-derived, adult human MSC with an intrinsic capacity to undergo endochondral ossification. By analogy to embryonic limb development, we hypothesized that successful execution of the endochondral program depends on the initial formation of hypertrophic cartilaginous templates. Human MSC, subcutaneously implanted into nude mice at various stages of chondrogenic differentiation, formed bone trabeculae only when they had developed in vitro hypertrophic tissue structures. Advanced maturation in vitro resulted in accelerated formation of larger bony tissues. The underlying morphogenetic process was structurally and molecularly similar to the temporal and spatial progression of limb bone development in embryos. In particular, Indian hedgehog signaling was activated at early stages and required for the in vitro formation of hypertrophic cartilage. Subsequent development of a bony collar in vivo was followed by vascularization, osteoclastic resorption of the cartilage template, and appearance of hematopoietic foci. This study reveals the capacity of human MSC to generate bone tissue via an endochondral program and provides a valid model to study mechanisms governing bone development. Most importantly, this process could generate advanced grafts for bone regeneration by invoking a "developmental engineering" paradigm.bone repair | endochondral ossification | hypertrophic chondrocytes | regenerative medicine | tissue engineering

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In elderly patients with spinal stenosis with degenerative spondylolisthesis, dynamic stabilization with the Dynesys system in addition to decompression leads to similar clinical results as seen in established protocols using decompression and fusion with pedicle screws. It maintains enough stability to prevent further progression of spondylolisthesis or instability. With the Dynesys system, no bone grafting is necessary, therefore, donor site morbidity can be avoided.

In elderly patients with spinal stenosis and degenerative spondylolisthesis, decompression and dynamic stabilization lead to excellent clinical and radiologic results. It maintains enough stability to prevent progression of spondylolisthesis. Because no bone grafting is necessary, donor site morbidity, which is one of the main drawbacks of fusion is eliminated. However, the degenerative disease still is progressive and degeneration at adjacent motion segments remains a problem.

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