Treatment of benign, yet locally aggressive and highly recurrent tumors of the orofacial regions has been traditionally carried out, similar to other malignant diseases, with aggressive surgical removal resulting in major tissue loss, facial disfigurement, psychological and functionally debilitating sequelae. The overall goal of this proposal is to use new knowledge in stem cell biology to understand the behavior of these benign tumors and to develop new treatment approach using patient's own stem cells to restore defects in the orofacial regions.
Our group has demonstrated promising evidences that certain benign tumors of the orofacial bones, possess stem cell properties and are capable of regenerating disease-like bone when transplanted into mice. To our knowledge, this is the first demonstration of the disease animal model generated by human tumor stem cells, which will allow clinical testing and further understanding of the cause of benign tumors of bones. We propose to investigate the functional role of tumor stem cells, their local environment, and their interactions to elucidate the underlying mechanism of benign/locally aggressive tumors of the orofacial bones, toward the development of a less invasive, novel stem cell-based therapeutic approach to allow a better tissue and functional preservation in the orofacial complex.
The purpose of this planning grant is to bring together an outstanding, multidisciplinary Disease Team to develop a novel approach to treatment of benign orofacial tumors using the principles of stem cell biology associated with tumor pathology. The Disease Team will consist of experts in various clinical aspects of orofacial tumors, stem cell and developmental biologists, oral pathologists , and biomaterial engineers. Three major areas will be proposed: a solid basic science component focusing on the underlying mechanism of how stem cells contribute to benign orofacial tumors; a translational component aiming at development of disease animal models for testing novel stem cell based-therapies; and, a pre-clinical component to test safety and efficacy of stem cell-based therapies in preparation for the early clinical trial in the treatment of benign/locally invasive orofacial tumors.
Statement of Benefit to California:
There is a great clinical demand for developing more optimized approaches to repair facial defects caused by burns, trauma, genetic anomalies, and cancers. Benign tumors of the orofacial region are controversial in terms of treatment due to unknown pathology and unpredictable recurrence, and therefore, have been routinely managed aggressively with ablative surgical resection as malignant diseases, resulting in major tissue loss, facial disfigurement, psychological and functionally debilitating sequelae. The "safe margin" surgical approach reflects uncertainty and knowledge gap in tumor pathology and should be re-examined based on current knowledge of stem cell biology and organ development. A comprehensive understanding of the benign tumor disease will guide clinicians to refine current radical surgery towards a more tissue sparing/conserving approach, enable vital tissue preservation in the orofacial regions.
More importantly, Californians who are head and neck tumor survivors, or suffer esthetic and functionally debilitating orofacial defects will benefit from the advances in stem cell biology and its clinical applications, specifically in the field of orofacial reconstruction. In this proposal, we will expand current knowledge of tumor stem cell biology to elucidate pathology of benign tumors and test the feasibility of utilizing autologous stem cells in the reconstruction of osseous and continuity defects of the orofacial complex. The refined stem cell-based approach in the treatment of benign/locally aggressive orofacial tumors will replace standard paradigm of treatment which involves multiple surgeries, lengthy operating time, cost, and morbidity to the patients. The success of this proposal will not only benefit the people of California, but will have high impact on the state economy by reducing the medical cost and overall financial burden on the State of California Health Insurance.