Scottsdale, Az. — Research conducted at the Ospedale Civile Maggiore in Verona, Italy, indicates that adipose-derived adult stem cells (ADAS) vascularize and restore function in breast tissue marked by radiation-induced ischemic lesions.
Speaking at the 84th Annual Meeting of the American Association of Plastic Surgeons, here, Gino Rigotti, M.D., head of the surgery department, reports, "Early clinical outcomes were striking. We saw dramatic improvement or remission of symptoms in all evaluated patients, including those who had exhibited irreversible functional damage."
Also of note: irradiated patients treated with lipoaspirate have fewer problems with capsular contraction than nonirradiated patients.Dr. Rigotti believes the results could have broader applicability. In particular, he suggests ADAS might prove to be an effective, minimally invasive adjuvant therapy for angiopathies and ischemic diseases.
Previous research has established that stem cells contribute to restoration of tissue vascularization and organ function.
Scientists have reported significant results using bone marrow endothelial and hematopoietic stem cells after ischemic events in human limbs and myocardium.
Furthermore, human adipose tissue is known as a rich source of mesenchymal stem cells (MSCs) with multi-lineage potential. Animal research indicates that MSCs secrete angiogenic and antiapoptotic factors.
The work of Dr. Rigotti and colleagues with breast cancer patients confirms that: 1) ADAS will induce human angiogenesis in much the same fashion as cells derived from bone marrow; and 2) ADAS is an effective treatment for ischemic pathologies.
Serendipity guided discovery
"Everything started with a lady, who had a mastectomy and reconstruction with expander-implant," the surgeon tells Cosmetic Surgery Times. "She needed lipofilling to correct an imperfection in the medial aspect of her reconstructed breast and asked us to also correct a depression in the supraclavicular region caused by irradiation 20 years before. Previously, the patient had suffered from dermatitis, erythema, desquamation, telangiectasia and burning. After lipofilling, the skin returned almost to normal."
Dr. Rigotti and colleagues decided to perform an ultrastructural analysis on irradiated tissues and lipoaspirate with an electron microscope. They concluded that a radiolesion is a scleroderma-like ischemic disease. In the lipoaspirate, they found very few functional adipocytes; however, there was a well-preserved vascular-stromal cell fraction.
He emphasizes, "When we fill a region with lipoaspirate, we are not injecting adipocytes, which are dead or dying, but only vascular-stromal cells."
Next, the team placed the vasculo-stromal fraction in a centrifuge at 2700 rpm for 15 minutes, digested the extracellular matrix with collagenase, and centrifuged it again to produce a pure fraction for culture. A cytofluorimetric-based analysis determined that 2 cc of human lipoaspirates contains at least 1.8x103 MSCs/cc. The clonogenic fraction was 0.139 percent.
In 2002, Dr. Rigotti evaluated a group of 59 patients, who underwent post-surgical external adjuvant radiation therapy for breast cancer, enrolling the first 20 patients with grade 3 (severe symptoms) or grade 4 (irreversible functional damage) on the LENT-SOMA scale and no medical history of connective, metabolic or skin disease in a trial. Mean age was 50.9 years.
Since animal studies suggested benefits were dose dependent, the number of ADAS injections (one injection in five patients, two injections in eight patients, three injections in six patients, and six in one patient) was determined by the severity of radiation damage. Doses of injected purified lipoaspirate ranged from 60 to 80 cc. Areas targeted: supraclavicular region, anterior chest wall after mastectomy with or without breast prosthesis and breast after quadrectomy.
Following treatment, tissue was evaluated with an electron microscope. Previous indications of fibrosis had disappeared. Tissue became well hydrated and soft. New capillary vessels developed between normal adipocytes.
"This process favors the development of stem cells into mature adipocytes and produces a newly formed microcirculation to replace the existing, seriously damaged one," Dr. Rigotti tells Cosmetic Surgery Times.