Umadevi Kandalam, PhD
A Novel Strategy for Vascularized Bone Tissue Regeneration
Umadevi Kandalam, PhD is an Associate Professor of Physiology at the Woody L. Hunt School of Dental Medicine – Texas Tech University Health Sciences Center El Paso. Prior to this position, Dr. Kandalam was an Associate Professor in the Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL. She obtained her doctoral degree in biology. She is currently working in the field of Regenerative Medicine. Her research mainly focuses on mesenchymal stem cells for regeneration of bone tissue.
Recent advancements in the stem-cell based therapies offer a viable option for restoring bone defect. However, it is the insufficient vascularization poses challenge in bone regenerative approaches. Our long-term goal is to regenerate vascularized bone for the repair of critical size defects. We intend to use gingival mesenchymal stem cells (GMSCs) due to their ease of harvesting and minimal risk of immune-rejection, high proliferation capacity in ex vivo culture and the property to serve as an autologous stem cell source. In this study, we propose to use a novel approach of simultaneous transplanting ex vivo programed two types of GMSCs, i.e, angiogenic GMSCs and osteogenic GMSCs, to repair the calavarial defect in a rat model to regenerate vascularized bone. GMSCs express a unique dual functional molecule Sema4D which has angiogenic and anti-osteogenic effects. Our hypothesis is temporally controlled Sema4D release followed by neutralization of Sema4D in transplanted GMSCs will regenerate sufficiently vascularized bone. This hypothesis will be tested by two aims. In Aim 1, we will establish the role of Sema4D produced by gingival stem cells in inducing angiogenesis and inhibiting osteogenesis from gingiva derived stem cells in vitro. Aim 2 will evaluate the in vivo efficacy of generating vascularized bone by means of transplanting the programed angiogenic- and osteogenic-stem cells of which production of Sema4D will be temporally controlled by anti-Sema4D-mAb injection. Developing vascularized bone regeneration by transplanting the two types of programed gingiva derived stem cells in combination with mAb-based modulation of dual functional Sema4D represents a novel tissue engineering technique to reconstruct the robust and resilient bone in the oral and craniofacial region.