Juline Deppen

BME PhD Proposal Presentation

Date: September 10, 2019

Time: 2:00-4:00 PM

Location: HSRB E260

Committee Members:

Rebecca D. Levit, MD (Emory University School of Medicine) (Advisor)

Luke P. Brewster, MD, PhD, MA, RVT (Emory University School of Medicine)

Zhiyong Lin, PhD (Emory University School of Medicine)

John N. Oshinski, PhD (Emory University School of Medicine)

Krishnendu Roy, PhD (Georgia Institute of Technology, Biomedical Engineering)

Title: Assessing a cellular therapeutic strategy for peripheral artery disease in a swine model of limb ischemia

Abstract: Peripheral artery disease (PAD) is an age-related medical condition with limited treatment options in late-stage critical limb ischemia. Cell therapy may promote revascularization in ischemic limbs of PAD patients; however, clinical trials have shown minimal, if any, positive results. Many challenges exist for the successful translation of cellular therapeutics from bench to bedside. Small animal models are inadequate for assessing overall benefits, adverse reactions, and dosing. There is not a consensus large animal model of durable limb ischemia assessed through clinically applicable, quantitative techniques. Limited numbers of viable cells exist after free injection, and there is a lack of understanding of mechanisms and potency of different cell donors. We have previously shown that alginate-encapsulated mesenchymal stromal cells (eMSCs) promote functional benefits and immunomodulation through adenosine production via CD73 and increase limb perfusion in small animals.

Our overall objective is to assess the efficacy of eMSCs for treating PAD on a clinical scale. We propose the design of a porcine model of limb ischemia (Aim 1) allowing eMSC efficacy assessment (Aim 3) with 1) quantification of muscle blood flow, 2) evaluation of myopathy, 3) functional assessment, and 4) MSC tracking capabilities. Additionally, we aim to correlate CD73 expression and function with human MSC potency (Aim 2). This work will facilitate the successful translation of eMSCs and other cell therapies from bench to bedside for PAD patients.