Adipose-Derived Stem Cells Show Promise in Breast Reconstruction

 Results Reported at the 30th San Antonio Breast Cancer Symposium -December 15, 2007, San Diego, CA - Cytori Therapeutics (NASDAQ: CYTX) received results from an independent, investigator-sponsored study in Japan in which adipose tissue-derived stem and regenerative cells were used for breast reconstruction following partial mastectomy. The study data were presented today at the 30th San Antonio Breast Cancer Symposium (Poster #4071).

The novel procedure evaluated 21 women with no metastases or recurrence at least one year after partial mastectomy. Among key findings:

• The procedure was reported safe and well tolerated in all women
• No rejection or immune response was observed
• Patient satisfaction of the outcome was 79 percent, with a mean follow up period of 7.7 months
• There was a statistically significant improvement in average breast tissue thickness at one month following treatment and at final assessment compared to baseline
• There was no significant loss of tissue thickness between one month and the final assessment

In the study, tissue loss resulting from partial mastectomy was reconstructed with each patient’s own liposuctioned fat, which was combined and enhanced with her own adipose-derived stem and regenerative cells. These cells were made available at the time of surgery using Cytori’s investigational device, the Celution™ System.

“This clinical series is an exciting, early development for women with breast cancer who undergo partial mastectomy,” said Marc H. Hedrick, M.D., president for Cytori Therapeutics. “The reported data suggest this novel procedure can be safely performed, is clinically practical for surgeons to implement, and confirms Cytori’s decision to initiate clinical trials intended to establish efficacy, ascertain volume retention, and measure the magnitude of aesthetic and functional improvement.

“Reconstructive options have not kept pace with the development of new cancer therapies and existing reconstructive options for women are either ineffective, impractical or both. Until now, partial mastectomy patients have had little hope other than to live with tissue loss. This procedure holds the potential to offer women the opportunity to restore the contour, volume and function lost during cancer treatment.”

Two clinical studies will be initiated next year in Europe by Cytori to further evaluate adipose-derived stem and regenerative cells, processed with the Celution™ System, in breast reconstruction following partial mastectomy. One study, RESTORE II, will evaluate up to 70 patients at multiple trial sites. A second study, VENUS, will be a 20-patient single center study in patients with more severe radiation damage and contour defects.

Fat, known medically as adipose tissue, is one of the body’s richest and most accessible sources of regenerative cells. Adipose-derived regenerative cells include adult stem cells in addition to other important cell types that have been shown pre-clinically to improve volume retention and graft persistence. For this reason, these cells potentially may improve and simplify traditionally complex fat transfer procedures as well as enable more predictable outcomes when applied to cosmetic and reconstructive surgery.  

More than one million women worldwide are diagnosed with breast cancer annually, including more than 370,000 women in Europe and more than 240,000 in the United States. Due to continual advancements in cancer detection, a growing percentage of women are eligible for partial versus full mastectomies. Unfortunately, partial mastectomy often results in significant skin damage, tissue loss, pain, and reduction or loss of motion. Women who undergo such procedures have limited reconstructive options to potentially reduce associated pain, reverse loss of motion, and restore breast volume and contour.  

Cytori Therapeutics

Cytori Therapeutics’ (NASDAQ: CYTX) goal is to be the global leader in regenerative medicine. The company is dedicated to providing patients with new options for reconstructive surgery, developing treatments for cardiovascular disease, and banking patients’ adult stem and regenerative cells. To reach its goal, Cytori is developing its innovative Celution™ System to separate and concentrate a patient’s own adult stem and regenerative cells from adipose (fat) tissue for these cells to be delivered back to the patient during the same surgical procedure. The Celution™ System will be introduced in 2008 in Europe for reconstructive surgery and launched in Japan for cryopreserving a patient’s own stem and regenerative cells. Clinical trials are ongoing or planned in cardiovascular disease, spinal disc degeneration, gastrointestinal disorders, and other unmet medical needs. www.cytoritx.com

Cautionary Statement Regarding Forward-Looking Statements
This press release includes forward-looking statements regarding events, trends and prospects of our business, which may affect our future operating results and financial position. Such statements are subject to risks and uncertainties that could cause our actual results and financial position to differ materially. Some of these risks and uncertainties include our history of operating losses, the need for further financing, regulatory uncertainties, dependence on performance of third parties, and other risks and uncertainties described (under the heading “Risk Factors”) in Cytori Therapeutics’ Form 10-K annual report for the year ended December 31, 2006. We assume no responsibility to update or revise any forward-looking statements to reflect events, trends or circumstances after the date they are made.

Contact:
Tom Baker   
858-875-5258   
tbaker@cytoritx.com

Cardiac Stem Cell Therapy Closer To Reality

ScienceDaily (Dec. 30, 2007) — Since the year 2000, much has been learned about the potential for using transplanted cells in therapeutic efforts to treat varieties of cardiac disorders. “Cardiac stem cell therapy involves delivering a variety of cells into hearts following myocardial infarction or chronic cardiomyopathy,” says Amit N. Patel, MD, MS, director of cardiac cell therapy at the University of Pittsburgh Medical Center and lead author of an overview and introductory article, Cardiac Stem Cell Therapy from Bench to Bedside. “Many questions remain, such as what types of cells may be most efficacious. Questions about dose, delivery method, and how to follow transplanted cells once they are in the body and questions about safety issues need answers. The following studies, contribute to the growing body of data that will move cell transplantation for heart patients closer to reality.”

According to Patel, special editor for this issue, suitable sources of cells for cardiac transplant will depend on the types of diseases to be treated. For acute myocardial infarction, a cell that reduces myocardial necrosis and augments vascular blood flow will be desirable. For heart failure, cells that replace or promote myogenesis, reverse apoptopic mechanisms and reactivate dormant cell processes will be useful.

“Very little data is available to guide cell dosing in clinical studies,” says Patel. “Pre-clinical data suggests that there is a dose-dependent improvement in function.”

Patel notes that the availability of autologous (patient self-donated) cells may fall short.

Determining optimal delivery methods raise issues not only of dose, but also of timing. Also, assessing the fate of injected cells is “critical to understanding mechanisms of action.”

Will cells home to the site of injury? Labeling stem cells with durable markers will be necessary and new tracking markers may need to be developed.

Improved cell survival drugs

Adult bone marrow-derived mensenchymal stem cells (MSCs) have shown great signaling and regenerative properties when delivered to heart tissues following a myocardial infarction (MI). However, the poor survival of grafted cells has been a concern of researchers. Given the poor vascular supply after a heart attack and an active inflammatory process, grafted cells survive with difficulty. Transmyocardial revasularization (TMR), a process by which channels are created in heart tissues by laser or other means, can enhance oxygenated blood supply.

“We hypothesized that using TMR as a scar pretreatment to cell therapy might improve the microenvironment to enhance cell retention and long-term graft success,” said Amit N. Patel, lead author of a study titled Improved Cell Survival in Infarcted Myocardium Using a Novel Combination Transmyocardial Laser and Cell Delivery System. “TMR may act synergistically with signaling factors to have a more potent effect on myocardial remodeling.”

Patel and colleagues, who used a novel delivery system to disperse cells in the TMR-generated channels in an animal model, report significant cell survival in the TMR+Cell group versus Cells or TMR alone. The researchers speculated that there was an increase in local production of growth factors that may have improved the survival of transplanted cells.

Stem cells depolarize

Recent studies have suggested that there are stem cells in the heart. In this study, researchers engineered mesenchymal stem cells (MSC) to over express stromal cell-derived factor-1 (SDF-1), a chemokine.

“Our study suggests that the prolongation of SDF-1 expression at the time of an acute myocardial infarction (AMI) leads to the recruitment of what may be an endogenous stem cell in the heart,” says Marc Penn, MD, PhD, director of the Skirball Laboratory for Cardiovascular Cellular Therapeutics at the Cleveland Clinic Foundation. “These cells may contribute to increased contractile function even in their immature stage.”

In the study titled SDF-1 Recruits Cardiac Stem Cell Like Cells that Depolarize in Vivo, researchers concluded that there is a natural but inefficient stem cell-based repair process following an AMI that can be manipulated through the expression of key molecular pathways. The outcome of this inefficient repair can have a significant impact on the electrical and mechanical functions of the surviving myocardium.

Grafting bioartifical myocardium for myocardial assistance

While the object of cell transplantation is to improve ventricular function, cardiac cell transplantation has had limited success because of poor graft viability and low cell retention. In a study carried out by a team of researchers from the Department of Cardiovascular Surgery, Pompidou Hospital, a matrix seeded with bone marrow cells (BMC) was grafted onto the infarcted ventricle to help support and regenerate post-ischemic lesions.

“Our study demonstrated that bone marrow cell therapy associated with the surgical implantation onto the epicardium of a cell-seeded collagen type 1 matrix prevented myocardial wall thinning, limited post-ischemic remodeling and improved diastolic function,” says Juan Chachques, MD, PhD, lead author for Myocardial Assistance by Grafting a New Bioartificial Upgraded Myocardium (MAGNUM Clinical Trial): One year follow-up.

“The use of the biomaterial appears to create a micro atmosphere where both exogenous and endogenous cells find an optimal microenvironment to repair tissues and maintain low scar production,” explains Chachques.

According to Chachques, the favorable effects may be attributed to several mechanisms. The BMC seeded in the collagen matrix may be incorporated into the myocardium through epicardial channels created at the injection sites. Too, the cell-seeded matrix may help prevent apoptosis.

“This biological approach is attractive because of its potential for aiding myocardial regeneration with a variety of cell types,” concluded Chachques.

Those cell types include skeletal myoblasts, bone marrow-derived mensenchymal stem cells, circulating blood-derived progenitor cells, endothelial and mesothelial cells, adipose tissue stem cells and, potentially, embryonic stem cells.

The full research articles are published in Cell Transplation (Vol.16 No. 9).

Adapted from materials provided by Cell Transplantation.

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