Many musculoskeletal diseases and syndromes result from deregulation of mesenchymal tissue differentiation or maintenance. Skeletal defects, such as those that result in craniofacial anomalies, can have a devastating impact.

Cleft palate and impaired suture closure of skull bones result from slight defects in mechanisms that direct tissue differentiation, but may not affect overall skeletal development. Metabolic skeletal diseases, including osteoarthritis (joint degeneration) and osteoporosis (loss of bone mineral), are common in the aging population. Bone repair is impaired in patients with metabolic diseases such as diabetes, and a segment of the normal population.

Insight into bone and cartilage development and repair will guide us in approaches to skeletal repair. Degenerative muscle diseases, such as muscular dystrophies, derive from defective regeneration of muscle stem cells and muscle repair and will benefit from novel strategies to restore muscle integrity.

Finally, patients with tooth-related defects would benefit from the use of dental pulp stem cells to generate tooth structures. Insight into the mechanisms of mesenchymal tissue differentiation, maintenance and pathology continues to lead to the development of new strategies for intervention in musculoskeletal diseases and syndromes, and soft and hard tissue repair processes.

This program in musculoskeletal biology combines efforts in different labs that seek to understand the generation of bone, cartilage and muscle tissue. This knowledge is instrumental for developing strategies to differentiate cells into these tissues to stimulate the repair and replacement of bone, cartilage, and muscle. Ongoing efforts focus on:

1. optimizing strategies to derive bone-depositing osteoblasts and cartilage-depositing chondrocytes from undifferentiated mesenchymal or embryonic stem cells
2. exploring the use of fat cells and their progenitors (that are easily derived from liposuction) as an autologous cell source to generate bone, cartilage and muscle cells
3. understanding the utility of bone marrow-derived mesenchymal stem cells, as a cellular environment for the differentiation of hematopoietic cell lineages
4. determining whether stem cells derived from tooth pulp can be used as an autologous source of cells for bone repair
5. characterizing embryonic and adult stem cell differentiation along the osteoblast, chondrocyte and myocyte lineages, and defining methods for bone, cartilage and muscle tissue engineering
6. developing osteo- and chondro-conductive carriers to facilitate and control generation and regeneration of bone and cartilage tissue in-vitro and in-vivo
7. creating strategies for the expansion of cartilage and bone tissues prior to clinical implantation or administration
8. developing strategies for the improvement of bone and cartilage tissue properties
9. utilizing preclinical models to measure success and optimize surgical techniques for tissue engineering therapies for osteoporosis, fracture healing, arthritis, and degenerative intervertebral disc disease.

Cell-based therapies are primarily designed toward

1. the replacement of cartilage, primarily in the treatment of osteoarthritis (replacement of joint cartilage) and the regeneration of intervertebral discs
2. replacement and regeneration of bone tissue in fractures with impaired healing capability, osteoporosis, and craniofacial repair
3. muscle repair and regeneration in patients with impaired muscle regeneration, such as in muscular dystrophy.

The transition from basic research to translational research and clinical trials is facilitated by the internationally recognized Department of Orthopedic Surgery, Center for Craniofacial Anomalies, and Department of Surgery, all of which have an extensive range of expertise with diverse patient populations and with patient-based research and clinical trials.

Participating Faculty and Labs