Darnell Kaigler, DDS, PhD

Stem cell mediated bone regeneration with allografts

Abstract
In recent years, stem cell therapies have gained increased attention for their potential to be used in treating challenging oral and craniofacial bone defects due to their regenerative potential. Despite their increasingly widespread use in medicine, regulatory barriers to their use remain in dentistry, particularly in the United States, due to regulatory benchmarks still needing to be met demonstrating their safety and efficacy relative to currently used allografts and biomaterials. In our prior work, we have shown that mesenchymal stem cells (MSCs) have the capacity to enhance bone regeneration in bone defects following transplantation. Further, we have evidence to demonstrate that oral MSCs (oMSCs) are more efficacious at regeneration of craniofacial tissues than MSCs derived from extraoral tissues (i.e. bone marrow). In this study, we aim to evaluate the efficacy and safety of delivering oMSCs on different allograft materials which are used in day-to-day clinical practice for craniofacial regeneration. Our hypotheses are that direct transplantation of oMSCs on allograft carriers is more efficacious than grafting of allografts alone, and that stem cell therapy is safe due to stem cells remaining localized to their site of transplantation. To test these hypotheses, the project has two straightforward Specific Aims (SAs). In SA1, we will evaluate the regenerative efficacy of commonly used allografts in craniofacial defects when combined with oMSC transplantation. In SA2, we will determine the safety of stem cell delivery by tracking fluorescently labelled oMSCs to determine if they remain localized in the site of their transplantation. Successful completion of the Aims of these translational in vivo studies will provide further evidence for the safety and efficacy of stem cell therapy. It will also address the existing unmet regulatory barriers for their day-to-day clinical utility when used in combination with allografts clinicians currently use in practice.