Breast cancer survivors might one day avoid the prospect of invasive breast reconstruction surgery, opting instead for an approach that would involve using stem cells derived from their own fat, suggest University of Pittsburgh researchers who are studying the potential these cells may have for regenerating new breast tissue.

In animal models, the researchers hope to prove that an injection of fat-derived stem cells that are seeded onto microscopic scaffold structures will enable the production of a durable, replacement soft tissue. The team, led by J. Peter Rubin, M.D., assistant professor of plastic and reconstructive surgery at the University of Pittsburgh School of Medicine, recently received a three-year grant from the National Cancer Institute to further explore this unique approach.

"The surgical options for breast reconstruction involve either the use of implants or a procedure whereby fat tissue taken from another part of the body is shaped into the form of a breast. Neither is ideal nor without risk. The use of adipose- or fat-derived stem cells may represent a better solution for soft tissue reconstruction in breast cancer patients," said Dr. Rubin, who also is co-director of the Aesthetic Surgery Center at the University of Pittsburgh Medical Center.

The use of stem cells to treat disease or regenerate tissue is believed to hold promise because of their potential to develop into different specialized cell types. Indeed, when exposed to specific conditions in the laboratory, fat-derived stem cells have been shown to differentiate into cells characteristic of those from tissues such as fat, bone, cartilage, nerve, muscle and blood vessels.

Dr. Rubin and his colleagues are focusing their efforts on an approach that involves combining the fat-derived stem cells with microscopic beads composed of a type of extracellular matrix (ECM) that has regenerative properties. Preliminary results indicate that the stem cells can easily attach themselves to these beads and are able to differentiate into mature fat cells. When injected under the skin in a rat model, the cellular combination eventually formed what they describe as a "mound" of tissue.

The fat-derived stem cells being used in the study are obtained from breast cancer patients.

"We need to demonstrate that fat-derived stem cells taken from a breast cancer patient behave no differently than those from other women. Moreover, our studies will seek to understand what effect, if any, these stem cells may have on cancer cells. A major question is whether they will in some way promote the growth of cancer cells. We certainly hope this proves not to be the case," Dr. Rubin cautioned.

In 2001, researchers from the University of California Los Angeles and the University of Pittsburgh first reported that adult stem cells could be isolated from adipose tissue, more commonly known as fat. Since then, laboratory studies have suggested adipose-derived stem cells have potential for treating heart attack, stroke or bone injury, although there have been no clinical trials in the U.S. to date. Experts estimate that one pound of whole fat removed in a tummy tuck, for example, can yield up to 200 million stem cells, which in culture can be expanded by 10 times over the course of two weeks. If and when fat-derived stem cells are tried in patients for breast reconstruction, Dr. Rubin predicts surgeons will obtain the cells from the patients' own stores of abdominal fat.

According to the American Cancer Society, more than 214,000 new cases of invasive breast cancer will be diagnosed by the end of 2006. For women who require mastectomy, the loss of one or both breasts can cause significant discomfort and psychosocial distress. More than 80,000 breast reconstruction operations are performed each year, according to American Society of Plastic Surgeons statistics.

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CONTACT: Clare Collins

Working with Dr. Rubin on the NIH-funded grant are co-investigators Kacey G. Marra, Ph.D., from the department of surgery, division of plastic surgery, School of Medicine, and the department of bioengineering, School of Engineering; Albert D. Donnenberg, Ph.D., from the department of medicine, division of hematology/oncology, School of Medicine, and the University of Pittsburgh Cancer Institute (UPCI); and Vera S. Donnenberg, Ph.D., of the department of surgery, School of Medicine and UPCI. Stephen Badylak, D.V.M., M.D., Ph.D., from the department of surgery, School of Medicine, and the University of Pittsburgh McGowan Institute for Regenerative Medicine; and Howard D. Edington, M.D., of the department of surgery, division of surgical oncology, School of Medicine and the McGowan Institute, are consultants.

Contact: Lisa Rossi
University of Pittsburgh Medical Center