Grants We Funded

Abstract
Cutaneous wound healing is a complex process that involves the orchestration of multiple different cell types to produce a functional biological patch. In the case of chronic wounds, factors such as local tissue hypoxia and ischemia-reperfusion injury (IRI) combine to impede the usual progression of these events and indefinitely forestall the healing process. Despite the advent of bioengineered skin products and recombinant growth factor therapies for the treatment of problem wounds such as venous stasis ulcers, pressure sores, and diabetic ulcers, many chronic wounds have proven refractory to these methods and continue to pose a great burden to the health care system in terms of both cost and time. We propose that mesenchymal stem cells (MSCs) represent a novel therapeutic approach for the treatment of chronic wounds based on their ability to function as intelligent bioactive agents of repair. Early reports have demonstrated that these cells are capable of fully integrating into the wound environment and, via either direct cellular differentiation or the context-dependent elaboration of signaling molecules, can not only enhance wound healing but also promote the development of more regenerative phenotypes. In our experiments, we aim to test the ability of adipose-derived stem cells (ASCs), a specific type of MSCs that are readily harvested from adipose tissue stores, to rescue healing deficits in two rabbit models of chronic wounds. These models include a previously established ischemic rabbit ear wound model as well as a novel rabbit ear wound model that employs a reversible arterial clamp for the induction of ischemia-reperfusion injury (IRI). The influence of ASCs on basic wound healing parameters will be rigorously compared with that of fibroblast controls for all studies and the fates of transplanted cells will then be analyzed with a strategy for GFP labeling.

Biography
Dr. Steinberg was born and raised in Marlboro, New Jersey but moved with his family to Coral Springs, Florida at the age of 10. Upon finishing high school, Dr. Steinberg traveled back up the east coast to attend college at Duke University. He graduated summa cum laude in 1999 with a degree in biomedical engineering. During his time at Duke, he worked on the design, construction, and analysis of transducer devices for a novel type of three dimensional ultrasound imaging. He also had the opportunity to work on a clinical project involving hematopoetic stem cell therapy for patients with advancedstage cancers. Following graduation at Duke, Dr. Steinberg enrolled in the Medical Scientist Training Program at Johns Hopkins University School of Medicine. After an initial two years of medical school, Dr. Steinberg began his graduate thesis research in the Department of Neuroscience. His doctoral dissertation, entitled “Cellular and Molecular Mechanisms of Long-Term Synaptic Depression in the Cerebellum” under advisor Richard L. Huganir, Ph.D., included a comprehensive analysis of the key events underlying a form of learning and memory in the cerebellum. Representing a turn from his previous areas of focus in engineering, this work in basic neuroscience enabled Dr. Steinberg to develop expertise in protein biochemistry, molecular biology, cell culture and histology, and genetic engineering including the generation of unique animal models. His work led to first author publications in journals such as Science, Neuron, and Proceedings of the National Academy of Sciences. Dr. Steinberg returned to clinical studies in 2005 and was later awarded both the M.D. and Ph.D. degrees from Johns Hopkins in 2007.