Breast cancer is endemic in the United States, with nearly 216,000 new cases expected this year (American Cancer Society statistics). For patients undergoing mastectomy,the loss of one or both breasts can cause significant discomfort and psychosocial distress. The number of breast reconstruction operations exceeds 80,000 cases per year (American Society of Plastic Surgeons statistics). Current surgical options including autologous tissue flaps and implants, have significant problems. The use of adipose precursor cells, or preadipocytes, may represent a better solution for soft tissue reconstruction for cancer defects. We hypothesize that human preadipocytes can be seeded on microcarrier scaffolds and be injected into an animal model to produce a durable engineered soft tissue replacement. Furthermore, we speculate that the preadipocytes will differentiate into both adipocytes and elements of the new vascular systemthat perfusesthe fat tissue.
The specific aims of this study are to: 1. Characterize cell surface markers of human preadipocytes using flow cytometry and assessthe variability of differentiation of cloned subpopulations. Preadipocytes will be isolated from adipose tissue of breast cancer patients for clinical relevance. 2. Evaluate the adherence, proliferation and adipogenic differentiation of human preadipocytes within macroporous collagenous beads and small intestinal submucosa (SIS) microparticles in culture. 3. Determine the ability of human preadipocytes to generate mature adipose tissue when seeded in collagen and SIS particles and injected subcutaneously into a nude mouse.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-SBIB-E (03))
Program Officer
Woodhouse, Elizabeth
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pittsburgh
Schools of Medicine
United States
Zip Code
Park, Tea Soon; Donnenberg, Vera S; Donnenberg, Albert D et al. (2014) Dynamic Interactions Between Cancer Stem Cells And Their Stromal Partners. Curr Pathobiol Rep 2:41-52
Philips, Brian J; Marra, Kacey G; Rubin, J Peter (2014) Healing of grafted adipose tissue: current clinical applications of adipose-derived stem cells for breast and face reconstruction. Wound Repair Regen 22 Suppl 1:11-3
Kelmendi-Doko, Arta; Marra, Kacey G; Vidic, Natasa et al. (2014) Adipogenic factor-loaded microspheres increase retention of transplanted adipose tissue. Tissue Eng Part A 20:2283-90
Ihunnah, Chibueze A; Wada, Taira; Philips, Brian J et al. (2014) Estrogen sulfotransferase/SULT1E1 promotes human adipogenesis. Mol Cell Biol 34:1682-94
Bustos, Martha L; Huleihel, Luai; Meyer, Ernest M et al. (2013) Activation of human mesenchymal stem cells impacts their therapeutic abilities in lung injury by increasing interleukin (IL)-10 and IL-1RN levels. Stem Cells Transl Med 2:884-95
Kling, Russell E; Mehrara, Babak J; Pusic, Andrea L et al. (2013) Trends in autologous fat grafting to the breast: a national survey of the american society of plastic surgeons. Plast Reconstr Surg 132:35-46
Zimmerlin, Ludovic; Park, Tea Soon; Zambidis, Elias T et al. (2013) Mesenchymal stem cell secretome and regenerative therapy after cancer. Biochimie 95:2235-45
Fisher, Christine; Grahovac, Tara L; Schafer, Mark E et al. (2013) Comparison of harvest and processing techniques for fat grafting and adipose stem cell isolation. Plast Reconstr Surg 132:351-61
Zimmerlin, Ludovic; Rubin, J Peter; Pfeifer, Melanie E et al. (2013) Human adipose stromal vascular cell delivery in a fibrin spray. Cytotherapy 15:102-8
Philips, Brian J; Grahovac, Tara L; Valentin, Jolene E et al. (2013) Prevalence of endogenous CD34+ adipose stem cells predicts human fat graft retention in a xenograft model. Plast Reconstr Surg 132:845-58

Showing the most recent 10 out of 27 publications