Efficacy and fate of Mesenchymal stem cells post-transplantation in rat calvarial bone defect model

The fate of autologous mesenchymal stem cell (MSC) after transplantation for bone regeneration purpose is poorly understood. In this in-vivo study, we aim to evaluate the response/course of cell therapy by characterizing the grafted MSCs in terms of safety, immunomodulation, and role in new bone formation. We will use single-cell mass cytometry to serial whole-blood samples of rats undergoing cell therapy and comprehensively characterize the phenotypic and functional immune response to surgical intervention. As a safety parameter, and to study potential endogenous mobilization of MSC, quantification of these cells in circulation before and after administration in-vivo becomes imperative and of urgent need. Such mechanistic understanding of stem cell-host immune interactions might be helpful in overcoming barriers to clinical translation and developing novel single molecule-based therapeutics that simulate stem cell actions. In an attempt to reduce total number of animals, two calvarial bone defects per animal will be made. All experiments will be performed under the appropriate analgesic/anaesthetic protocols to minimize pain and distress. Animals will be monitored throughout the duration of the experiments to ensure minimal distress. The group has acquired sufficient expertise in rodent calvarial bone defect model and small animal imaging.