Dr. J. Peter Rubin wins McGowan Institute for Regenerative Medicine Grant of the Month | April 2015

J Peter Rubin
Injectable Engineered Tissue for Cancer Reconstruction
Breast reconstruction relieves physical discomfort and psychological distress following mastectomy for over 90,000 women in the United States annually. The limitations of the two main methods, autologous flap procedures and implant procedures, have driven a search for new reconstructive techniques. Autologous tissue operations are highly invasive with a prolonged recovery and risk for major donor site morbidity. Implant reconstruction avoids a donor wound, but is fraught with problems of scar contracture (20%), displacement (5%), rupture (5% in 5 years), and an overall reoperation rate of 50%. Additionally, both these therapies are poorly suited for the significant number of women with deformities after lumpectomy.

An effective method of minimally invasive autologous breast reconstruction will be paradigm changing. Minimally invasive methods of breast reconstruction based on aspirating and reinjecting fragmented adipose tissue have become a clinical reality and gained widespread use. Survey data published by our group show that 70% of US plastic surgeons are performing autologous fat transfer (AFT) injections in breast reconstruction. However, the oncologic safety of this therapy is unclear. In-vitro reports are concerning and suggest that adipose stem cells can induce breast cancer cell proliferation, but initial clinical reports are discordant and do not suggest higher recurrence rates. Our central hypothesis is that disaggregated adipose tissue can be injected to produce a durable soft tissue replacement with low oncologic risk. Moreover, we can develop an injectable reconstructive therapy that is in itself tumor suppressing. The specific aims are:

Aim 1: Characterize adipose tissue from cancer patients to determine paracrine “potency” and assess the interaction between breast cancer cells and adipose tissue components (individual cell types and intact adipose) in-vitro. We will isolate adipose stromal cells (ASCs), mature adipocytes, and disaggregated fat particles as used for AFT from abdominal subcutaneous fat of 30 patients undergoing breast reconstruction, and analyze the secretome and interactions with cancer cells in-vitro.

Aim 2. Assess the interactions between injected adipose tissue and breast cancer tumor cells in an animal model. In our mouse model of mammary pad tumor growth, cancer cell lines are injected, followed by injection of fat from 10 of the 30 subjects in AIM 1 to simulate the clinical scenario of AFT in a breast with residual disease.

Aim 3. Develop and test an injectable engineered tissue for cancer reconstruction that is also a local tumor suppressing therapy. In this highly innovative approach, we will use our polymer microencapsulation methods to deliver the commonly used chemotherapeutic agents, paclitaxel, doxorubicin, tamoxifen, and aromatase inhibitors within the injected adipose tissue.
National Cancer Institute, NIH
Budget Period: 04/08/2015 – 03/31/2016
Project Period: 04/08/2005 – 03/31/2020