Preclinical safety study shows adipose-derived stem cells improve heart function after heart attack

MacroPore Biosurgery, Inc. (Frankfurt: XMP) today announced that adipose tissue-derived regenerative cells improved heart function following myocardial infarction in a large-animal preclinical safety study. This study, performed in swine, confirms previous preclinical work by MacroPore Biosurgery and others suggesting that the Company’s proprietary, patented technology is safe and may be clinically useful in treating heart disease. The goal of the study was to determine the safety of adipose tissue-derived regenerative cells delivered into coronary circulation without cell culture. The results were presented in a poster presentation at the Transcatheter Cardiovascular Therapeutics 2004 meeting in Washington D.C. (Abstract # 550778).

Intracoronary infusion of adipose tissue-derived regenerative cells 48 hours after infarction was found to be safe, with all 13 swine surviving to the 6-month follow-up period. Additionally, the study demonstrated a statistically significant improvement in left ventricular ejection fraction (LVEF) at six-months post-infarction in the treated group over the control group, as measured by 2D echocardiography. Similar trends were observed by measuring LVEF via cineangiography, as provided in the data table below. LVEF is a measure of the heart’s ability to pump oxygenated blood throughout the body. It specifically determines the fraction of blood that is ejected out of the left ventricle with each contraction.

“We are encouraged by the findings from this preclinical study, which suggest that delivery of autologous, adipose tissue-derived, regenerative cells is safe and effective in preserving left ventricular systolic function,” said John K. Fraser, Vice President, Research and Technology, of MacroPore Biosurgery. “Despite the fact that this study was designed primarily to evaluate the safety of dose escalation in limited infarcts, we observed statistically significant improvements in heart function. Additional swine studies are underway to better understand and optimize dosing and efficacy in order to lay the foundation for clinical work.”

MacroPore Biosurgery and other investigators from around the world have shown that adipose tissue is a rich source of autologous regenerative cells. Adipose tissue-derived regenerative cells consist of (1) adult stem cells, (2) endothelial progenitor cells (blood vessel forming cells) and (3) other growth factor producing cells (tissue growth and repair promoting cells). These cells have practical benefits over other sources of regenerative-capable cells such as bone marrow, skeletal muscle, embryonic and fetal tissue and rarer sources of stem cells. Additionally, regenerative cells from a patient’s own adipose tissue (autologous-use) present no risk of rejection or disease transmission and avoid ethical concerns.

The methods used in the pre-clinical study are as follows: Infarcts were induced in 13 juvenile swine by balloon occlusion of the mid left anterior descending artery. Forty-eight hours after the infarction, adipose cells were harvested through a lipectomy, autologous regenerative cells were isolated, and the pigs were randomized to either an intracoronary infusion of saline (control) or 40-140×106 (mean 67.5×106) regenerative cells (experimental) infused distal to the site of occlusion. All 13 pigs (7 experimental, 6 control), survived to the 6-month follow up period. Left ventricular cineangiography and 2D echocardiography were performed at baseline, immediately post-infarction, and at six months. The table below summarizes the study results:

2D Echocardiography

LVEF at Baseline
Treated = 46%
Control = 47%

LVEF at 6-Months
Treated = 49%
Control = 38%

Change in LVEF
Treated = + 3%
Control = – 9%

Standard Deviation
Treated = + 6%
Control = + 5%

P-value = 0.01

Cineangiography

LVEF at Baseline
Treated = 51%
Control = 49%

LVEF at 6-Months
Treated = 55%
Control = 47%

Change in LVEF
Treated = + 4%
Control = – 2%

Standard Deviation
Treated = + 5%
Control = + 7%

P-value = 0.16

This press release may include forward-looking statements regarding events and trends which may affect MacroPore Biosurgery’s future operating results and financial position. Such statements are subject to risks and uncertainties that could cause MacroPore Biosurgery’s actual results and financial position to differ materially. These risks and uncertainties are described (under the heading “Risk Factors”) in our 2003 Form 10-K annual report for the year ended December 31, 2003, which is available on our web site. MacroPore Biosurgery assumes no responsibility to publicly release the results of any revision of forward-looking statements to reflect events, trends or circumstances after the date they are made.