Year of Publication

2016

Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation

College

Medicine

Department

Behavioral Science

First Advisor

Dr. Henry C. Vasconez

Abstract

Fat grafting is a common surgical procedure that involves the transfer of fat from one area of the body to another in order to improve contour deformities, such as in breast reconstruction. Advantages of the technique include using autologous tissue rather than a foreign body and the added benefit of having liposuction to remove fat from an undesirable location. Although adipose tissue could be the ideal soft tissue filler, fat grafting is plagued by tremendous variability in long-term retention, with volume survival rates of 20-80%, resulting in suboptimal outcomes and repetitive procedures.

The mechanisms contributing to long-term fat graft survival and resorption are not well understood. The discovery of multipotent mesenchymal adipose tissue-derived stem cells (ASCs) in subcutaneous adipose tissue has encouraged the study of their role in fat graft survival. ASCs are observed to survive after grafting, and in fact play a major role in adipocyte survival, regeneration and differentiation through adipogenesis and paracrine effects. In fact, lipoaspirate supplemented with ASCs has been shown to improve angiogenesis and long-term graft retention through the release of factors. Many adipose graft enrichment strategies encompassing growth factors, platelet-rich plasma, stem cells, gene therapy and tissue engineering have been attempted to augment and improve the viability of fat grafts. Therefore, a systematic review was undertaken to optimize safety and outcomes related to these enrichment strategies.

Recently, concerns have been raised from several regulatory bodies, including the FDA, regarding safety of fat grafting in the setting of breast reconstruction. ASCs within lipoaspirate have been postulated to create an inflammatory tumor microenvironment, to encourage angiogenesis, and to potentially contribute to tumorigenesis. Therefore, a review of both local data and a systematic review was undertaken to determine oncological outcomes of fat grafting to the breast.

Finally, we test the hypothesis that ASCs derived from obese donors exhibit compromised ASC functionality, leading to reduced fat graft retention when compared to non-obese subjects. Collectively, the studies that comprise this dissertation generate and critically appraise evidence for the safety, efficacy and outcomes of fat grafting in the setting of breast reconstruction.

Digital Object Identifier (DOI)

http://dx.doi.org/10.13023/ETD.2016.350

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