Profile and Department: Professor, Faculty of Dentistry, University of Toronto
Lab: Hinz Lab
Clinical approaches implanting differentiated or pluripotent stem cells or introducing biomaterials to engineer damaged and fibrotic tissue most often have to cope with the special cellular, chemical and mechanical environment created by resident repair cells, called myofibroblasts. Myofibroblasts are enigmatic cell types characterized by heightened tissue remodeling capacity. The presence of these cells is critical for appropriate tissue healing, yet their deregulation has been associated with fibrosis and contracture. The outcome of this ‘uncontrolled remodeling’ contributes to the destruction of vital organs such as heart, liver, kidney and lung, as well as scleroderma and hypertrophic scars (e.g. after burn injury).
In regenerative medicine, myofibroblasts simultaneously demonstrate a potential benefit while posing a major threat. For example, these reparative cells have shown promise in returning functionality to weak or failing organs when routine repair mechanisms of our body fail. Alternatively, these cells can also differentiate from tissue-delivered mesenchymal stem cells (MSCs) or from fibroblasts activated by engrafted biomaterials, e.g. breast implants. The consequence of the presence of these cells is implant failure due to tissue contracture, requiring repeated surgery/therapy. The consequence of MSC-to myofibroblast differentiation is loss of regenerative potential and worsening of fibrotic conditions. Therefore, we aim in identifying the mechanical and biochemical regulators that promote desired aspects of healing without stimulating detrimental side effects.