Dr. Joel Aronowitz is the surgeon who performed the groundbreaking Cell-Assisted Lipotransfer procedure on Suzanne Somers.
His new clinical trial, of which Suzanne Somers is the first enrollee, is based on promising earlier results of Kotaro Yoshimura, MD, and colleagues in Japan.
In their pioneering paper published in Aesthetic Plastic Surgery,* Dr. Yoshimura's group reported that their best procedure, which is similar to Dr. Aronowitz's method but involved less enrichment of stem cells in the transplant, increased breast size by more than twice as much as fat transfusion alone six months after the treatment (4-8 cm versus 2-3 cm).
This calculation is based on an increase in the difference between chest circumference at the nipple level and chest circumference just under the breast. The improvement was apparently due to less loss of injected mass when the transplanted fat was enriched in stem cells.
Dr. Aronowitz's method builds upon and extends these initial promising results and is believed to be the first such method to be introduced in a clinical trial in the United States. In addition, whereas the Yoshimura trial examined women who used this procedure only for cosmetic enhancement, Dr. Aronowitz's trial explored Cell-Assisted Lipotransfer for the first time in a post-lumpectomy patient, where there was severe post-radiation damage to the breast.
In this exclusive interview, Life Extension research scientist Greg Fahy, PhD, discusses the scientific intricacies of this procedure with Suzanne's surgeon Joel Aronowitz, MD.
Dr. Grag Fahy (GF): Dr. Aronowitz, from what Suzanne described, the therapy you administered depends on stem cells that are naturally present in abdominal fat. How plentiful are these stem cells?
Dr. Joel Aronowitz (JA): Suzanne's operation is a paradigm shift in surgery because it is natural regrowth of her breast based on the specific cells which control and direct repair and regeneration. All tissues of the body contain cells which direct regeneration after injury and replace aged cells over time. For example, cardiac muscle contains stem cells in a ratio of 1:40,000 (or one stem cell for each 40,000 mature cardiac cells). The subcutaneous fat of the abdomen and hips contains a much higher concentration of stem cells by comparison, about 1:4 (or one stem cell for each 4 fat cells). These stem cells in fat tissue are therefore very plentiful. In numbers, Suzanne's abdominal and hip fat contains about 1,000,000 stem cells per cubic cm of tissue. These cells are identified by size and immunologic markers such as CD34 on flow cytometry.
GF: Are these mesenchymal stem cells?
Stem cell manipulation
JA: Yes, they are mesenchymal type cells. This means that they are capable of differentiating into a wide variety of tissue types with the right stimulation. In this process we do not add any unnatural or outside stimulation to direct differentiation toward a specific tissue type. Since the adipose-derived cells we are using ordinarily live in fat of the abdomen and hips and are placed into the fat tissue of the breast, the signals they receive naturally stimulate them to regenerate fat tissue, the perfect tissue to fill a woman's breast.
GF: Are these stem cells naturally present in the breast as well?
JA: The breast does contain some of these cells, but in lower concentrations because fat makes up only a fraction of the tissue in a typical breast.
GF: You first separated the stem cells from abdominal fat cells so you could give them back in concentrated form. How much more concentrated were the stem cells when they were re-injected than when they were residing unconcentrated in normal fat?
JA: I harvested a total of 1,000 cubic centimeters (cc) of Suzanne's adipose tissue using a liposuction technique modified for the unique nature of this special operation. We took 400 cc of the fat, washed and prepared for grafting, and the remaining tissue was used to extract the stem cells. The separation process is done routinely in the laboratory, but for Suzanne's case we used a special laboratory system assembled in the operating room. The cells were concentrated from a volume of 600 cc of fat tissue to 5 cc's of adipose-derived stem cells.
GF: A liter (1000 cc) of fat is considerable. Are there some women who might not have enough body fat to enable them to take advantage of the procedure you performed?
JA: Our full study will be the first to use stem cell enhanced fat grafts to achieve full breast regrowth in a direct, controlled, comparison study. Since Suzanne is the first participant, I wanted to have as many stem cells as possible to demonstrate the effect of the stem cells on both the volume of the breast regrowth and improvement in the quality of the radiated skin. Most women have adequate extra fat tissue. One thousand cc equals only 2.2 lbs of fat, and most women consider the liposuction harvest a positive side effect of the procedure. Future study participants, however, will include women with only 100 to 200 cc of extra fat.
GF: How many patients are planned for your full study?
JA: Our initial design is slated for 100 patients.
GF: How soon after a lumpectomy or mastectomy can this treatment be applied?
JA: In the future, it should be possible to apply the procedure as soon as six weeks after breast cancer surgery, or ultimately, even immediately. However, in my study, the patient has to be 5 years beyond breast cancer surgery in order to be enrolled.
GF: If a woman wants to enroll in your study, is there any cost to her to do so?
JA: The study allows for no cost or reduced cost to the patient in certain circumstances. Many patients who have a serious breast deformity as a result of surgery or congenital condition will find that their health insurance covers a portion of the cost. While we will strive to keep the expenses reasonable, other patients in the current study will bear the cost themselves.
GF: To review, you collected 1,000 cc of fat and gave back 400 cc of fat plus 5 cc of purified stem cells. But if the original 400 cc of fat contained approximately 100 cc of stem cells (ignoring size differences between fat cells and stem cells), your stem cell enrichment was only about 5% beyond just transplanting ordinary fat. What was the rationale for that approach?
JA: This surgery, for the first time, is based on a new understanding of cellular function and uses a cellular approach. The number of stem cells in the 400 cc of fat injected is approximately 400 million. Our technicians obtained approximately 400 million additional cells from fat that would have been discarded otherwise. These 400 million cells fit into a small test tube because they are separated from unneeded connective tissue and much larger mature fat cells. The number of stem cells in the fat graft was therefore actually doubled in comparison to ordinary fat, the ratio of stem cells to fat cells increasing from 1 to 4 to 1 to 2.
GF: Is the main function of the stem cells in this procedure to speed the growth of new blood vessels, or do they also participate in reconstructing normal breast structure?
JA: Evidence points to stem cells as beneficial in several ways. First, they are believed to reduce inflammation. Second, they stimulate regrowth of small blood vessels. Third, these cells appear to direct surrounding cells to regenerate the architecture of adipose (fat) tissue, even directing the differentiation of white blood cells such as macrophages to become adipose cells. Finally, adipose tissue stem cells can differentiate into fat cells. They do not direct growth of breast tissue with ducts and glands, rather they produce adipose or fat tissue.
GF: Were you able to observe any clear signs that the stem cell augmentation improved the outcome in comparison to what would be expected for fat cell transplantation alone? Or will that take more time?
JA: The qualitative results of this procedure are striking, an improvement in the texture and appearance of the radiated skin, the softness of the damaged breast and an immediate and lasting significant increase in volume. My opinion, supported by a host of other credible physicians, is that our study will help to demonstrate the advantages Suzanne immediately recognized after her surgery over fat grafting alone in a scientific manner recognized by our thoughtful and appropriately cautious medical community.
GF: The breast contains a lot more than just fat and blood vessels. It also has a lot of fibrous tissue that helps to give it suppleness, a normal texture, and shape. How were you able to restore a natural shape without this tissue, and does the fibrous structure of the breast eventually grow back?
JA: Fortunately, Suzanne's previous breast cancer surgery preserved the basic shape of her breast and this contributed to her excellent result. We know from prior study in the laboratory that stem cells direct the regeneration of the complex tissue architecture of adipose tissue. The fibrous connective tissue is also regrown and supports the adipose tissue in Suzanne's regenerated breast. Of course, the breast glandular and ductal cells are not present in the graft and are not regrown by the stem cells.
GF: The way Suzanne described her experience, you were able to restore her breast to close to its normal volume and shape in a single operation. That is extraordinary. Were there any small changes in breast size after the initial operation caused, for example, by either cell division or cell death before new blood vessels could grow back in, or maybe by temporary inflammation?
JA: Suzanne's breast appeared almost normal in size and shape immediately after surgery. She actually was very excited when she took a peek at her breast in the recovery room. The natural fat regrowth gradually replaced the postoperative swelling over a period of 6-8 weeks postoperatively. This is the expected postoperative course experienced in the cases of our collaborator, Dr. Yoshimura, at the University of Tokyo.
GF: How much breast bruising and pain is associated with this procedure, and how long does it last?
JA: Suzanne experienced some pain and bruising of the breast and donor site in the abdomen and hips. The bruising resolved within 2 weeks, and mild bruising lasting 2 weeks is typical.
GF: There seems to be considerable evidence that fat-derived stem cells can stimulate the regrowth of small blood vessels in the breast, which may be why the procedure works so well to preserve the transplanted fat cells. However, these blood vessels might also provide oxygen, nutrients, growth factors, and other forms of support to any residual cancer cells that might have been missed by the surgeon. Could this be a cause for concern?
JA: All remaining breast tissue is at risk for developing recurrent or new breast cancer regardless of how it may be treated. This is why I teach oncologic surgeons that it is best to remove as much breast tissue as possible, whether we label the procedure lumpectomy, mastectomy, or breast conservation. The principle is removal of as much breast tissue as possible because it too frequently develops cancer, but with conservation of the external skin envelope in which the breast resides so that it can be re-filled with soft natural fat tissue, which rarely forms cancer itself. Even if cancer cells remain after removal of the tumor, there is no indication that fat grafts assist the growth of these abnormal cells even though normal fat grafting involves a lower but still significant concentration of stem cells. As a standard procedure for a variety of reconstructive and cosmetic purposes, no evidence is reported of a cancer-causing or stimulating effect of fat transplants. Fat simply rarely becomes cancerous. Of course, a woman with active breast cancer is not a candidate for cell-assisted regrowth of her breast or any other breast reconstruction procedure. The cancer must be removed first.
GF: Would you recommend this procedure to most women who require breast reconstruction?
JA: I have spent much of my career working to improve the results of breast cancer surgery and have been active in stem cell research with my partners here at Cedars-Sinai, Hollywood Presbyterian Hospital, and USC, as well as my colleagues in Korea and Japan. Adipose-derived stem cells were first identified here in Los Angeles and much important basic research was done in America. Regulatory barriers to clinical translation of this research slowed our progress compared to the common use of stem cells abroad. I hope that our groundbreaking study, and Suzanne's tenacity in seeking out this new treatment for breast regrowth and courage in being our very first study participant will empower other women to insist on the best option for their situation. Currently, women have a choice of an implant or a fairly invasive flap operation for reconstruction of the breast. This operation will add another option, not reconstruction but actual regrowth of the breast. When this method is combined with oncoplastic surgery to remove cancer or high risk breast tissue prophylactically, women will be able to have a fully regrown, natural breast. I think our study and future research will demonstrate that this operation is an attractive option for the majority of women who are treated surgically for breast cancer and for women who seek to have a prophylactic mastectomy because of a high risk of breast cancer.
GF: Thank you, Dr. Aronowitz.
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While preliminary cosmetic results appear promising with Cell-Assisted Lipotransfer (CAL), an advanced and novel method of adipose-derived stem cell enrichment of autologous fat for transplantation, long-term results are still uncertain until sufficient numbers of patients have the procedure and are subsequently followed. CAL appears to improve graft survival, likely due to the increased potential for angiogenesis and neovascularization (new blood vessel formation) with adipose-derived stem cells. This capacity for new blood vessel formation within the transplanted fat enriched with adipose-derived stem cells seems to enhance graft viability. However, given the potential for angiogenesis, and the known role of new blood vessel formation in tumor growth and proliferation, CAL should not be performed in patients with active cancer, or any evidence of ongoing malignancy. As with any new medical technology, safety must be evaluated over time.