Grants We Funded

Abstract
Autologous fat grafting has been used to correct soft tissue deformities for over a century. While there are many clinical applications of fat grafts, the focus of this proposal is to investigate its effect on preventing and correcting radiation skin tissue injury. While there have been some groups, including ours, that have studied the effects of autologous fat grafts and isolated adipose derived stem cells on radiation damaged skin and radiation wounds, no one has systematically examined the effect of the acellular extracellular matrix and/or the cytokines contained within it on radiated skin. Since it is now possible to separate the cells from the adipose matrix (de-cellularization), we intend to investigate this knowledge gap. Moreover, an off the shelf version of decellularized allograft fat has been recently been made available for human use and is being used in the clinical setting as an alternative to autologous fat graft (Renuva; MTF Biologics, Edison NJ). The increased use of this type of product in clinical practice provides additional stimulus for this timely and relevant proposal. Thus, the following aims are proposed: Aim 1: Using a proteomic approach, we will characterize the type and relative amounts of pro-wound healing extracellular matrix proteins and growth factors/cytokines in three distinct adipose-derived preparations: 1) freshly isolated fat (containing native cells) 2) de-cellularized fat and; 3) Renuva - off the shelf de-cellularized concentrated allograft tissue matrix. We hypothesize that freshly isolated fat will maintain the greatest concentration and diversity of ECM associated factors and proteins due to lack of chemical manipulation. We also hypothesize that Renuva will contain greater concentrations of ECM associated factors (per gram) than de-cellularized fat due to the fat that it exists in a concentrated powder form. Aim 2: Using an established animal model, we will study the differential in vivo effects of 1) freshly isolated fat; 2) de-cellularized fat and; 3) Renuva de-cellularized allograft tissue matrix on radiation induced skin injury and delayed wound healing. We hypothesize that freshly isolated adipose tissue will be superior to the acellular isolates and that the commercially-produced Renuva will outperform the de-cellularized fat due to higher concentrations of ECM components in Renuva allograft tissue matrix.

Biography
I am a plastic surgeon-scientist at the Keck School of Medicine of University of Southern California with an independent research laboratory at the USC Institute for Genetic Medicine. My time/effort allocation to research is 75%. My laboratory studies basic and translation aspects of lymphedema using clinically relevant murine models. In 2012, Dr. Young-Kwon Hong and I discovered that 9-cis retinoic acid stimulates lymphangiogenesis in vitro and in vivo. We are currently exploring a role for 9-cis retinoic acid in the pharmacologic treatment of surgically induced lymphedema. Our work has been published in journals such as Circulation and Annals of Surgery and has been supported by grants from the Southern California Clinical Translational Science Institute, Whittier Foundation, and the NIH.