CorMatrix Announces Publication of Pre-Clinical Data in Journal of American College of Cardiology (JACC) Demonstrating the Role of CorMatrix ECM(TM) Technology in Remodeling Cardiac Tissue

ATLANTA, March 16 /PRNewswire/ -- CorMatrix Cardiovascular, Inc., a medical device company dedicated to developing and delivering unique extracellular matrix (ECM) biomaterial devices that harness the body's innate ability to repair damaged cardiovascular tissue, announced today that investigators from the Mercer University School of Medicine, Emory University and CorMatrix Cardiovascular, Inc. demonstrated that an injectable emulsion of the company's ECM Technology enhances angiogenesis (new blood vessel growth), improves cardiac function, and increases the recruitment of bone-marrow derived (c-kit positive) stem cells, myofibroblasts, and macrophages in a rat model of myocardial infarction (heart attack).  The research, published in the March 23 print version of the Journal of the American College of Cardiology, was posted today on the Journal's website (http://content.onlinejacc.org).

"What is significant about our approach, compared to other attempts at developing stem-cell therapies for treating damaged heart tissue, is that we're able to avoid the pitfalls associated with trying to manipulate the individual cell types involved by allowing the ECM to naturally support the individual phases of tissue remodeling," said Robert G. Matheny, MD, Chief Scientific Officer of CorMatrix, and a co-author on the study. "Results from this study and previous work that we've done show that the adjacent healthy tissue is capable of supplying the correct cells and other factors needed for all phases of tissue reconstruction and regeneration. To do their work, the tissue cells simply need a physiologically correct, biologically supportive microenvironment, which our unique ECM Technology provides."

In the study, the heart muscle damage was caused by delivery of 45 minutes of reversible coronary occlusion. CorMatrix ECM emulsion or saline control was then injected into the affected ischemic myocardium. After three, seven, 21 and 42 days of reperfusion, the affected areas were analyzed for histological and molecular markers of cardiac remodeling, cellular recruitment and cardiac function.

Key Study Findings and Conclusions

• Expression of stem cell factor (SCF) was significantly increased in damaged heart tissue injected with ECM emulsion, and remained elevated throughout the study compared to the control. SCF has been previously reported to enhance endogenous cardiac repair by recruiting bone marrow-derived stem cells and other differentiated precursor cells, modulating stem cell differentiation, and stimulating expression of vascular endothelial growth factor (VEGF), a key regulator of angiogenesis.(1-2)
• Consistent with the time course of SCF expression was an observed increase in the number of c-kit positive cells found in the region injected with the ECM emulsion. c-kit is a well-known molecular marker for bone marrow-derived stem cells.
• New blood vessel formation in the ECM emulsion treated area was significantly enhanced relative to the control, as evidenced by increased density of alpha-smooth muscle actin (SMA) positive blood vessels.
• Consistent with enhanced angiogenesis, the ECM emulsion promoted infiltration and sustained accumulation of alpha-SMA expressing myofibroblasts and macrophages, whereas the accumulation of myofibroblasts declined after day seven in the control animals. Increased levels of VEGF protein expression and immunoreactivity were also observed.
• The wall thickness of the infarcted middle-anterior septum in the area of ECM emulsion injection was significantly increased relative to the control. Echocardiography showed significant improvements in fractional shortening, ejection fraction and stroke volume in the ECM emulsion group.
• The authors conclude that the data provides direct evidence that adverse cardiac remodeling can be modified by supplying CorMatrix ECM emulsion to the affected myocardium following myocardial infarction.

"The results of this study are exciting and suggest that our ECM Technology, when delivered as an injectable form directly into damaged cardiac muscle, delivers results consistent to those observed from implantation of the sheet form of the product that is currently in commercial use for surgical repairs of the human heart," said Beecher Lewis, President and COO of CorMatrix. "While these are very early pre-clinical results, the ability to use our injectable ECM emulsion to potentially fix or reverse the underlying damage from a heart attack could have significant potential clinical benefits and further study is warranted."

About Extracellular Matrix Biomaterial

The unique properties of extracellular matrix biomaterials were discovered at Purdue University. The decellularized matrix material serves as a scaffold to allow adjacent tissues to deliver cells and nutrients to the matrix, which then differentiate into tissue-specific cells. The ECM material is gradually replaced, as the patient's own body reinforces and rebuilds the weakened site. During the repair, the matrix is naturally degraded and resorbed, leaving remodeled functional tissue where scar tissue or injured tissue would normally be expected.

The use of extracellular matrix materials in non-cardiovascular applications has established a significant foothold in soft tissue repair, wound management and orthopedic applications. The safety of extracellular matrices has been well established in a number of different clinical applications. The extracellular matrix has been studied extensively, with more than 500 published papers. Since 1999, an estimated 500,000 patients worldwide have received an extracellular matrix implant.

About CorMatrix ECM Technology

CorMatrix Cardiovascular holds an exclusive license from Purdue University to research, develop, manufacture and market naturally occurring ECM products for cardiovascular applications. The company currently has U.S. clearance and a European CE Mark for its ECM Technology as an implant for pericardial closure and for use in cardiac tissue repair.

About CorMatrix Cardiovascular, Inc.

CorMatrix Cardiovascular, a privately held company based in Atlanta, Georgia, is dedicated to developing and delivering innovative cardiovascular devices that harness the body's innate ability to remodel damaged tissue. For more information, visit www.cormatrix.com.

1) Fazel S, Cimini M, Chen L, et al. Cardioprotective c-kit+ cells are from the bone marrow and regulate the myocardial balance of angiogenic cytokines. J Clin Invest 2006;116:1865–77.

2) Fazel S, Chen L, Weisel RD, et al. Cell transplantation preserves cardiac function after infarction by infarct stabilization: augmentation by stem cell factor. J Thorac Cardiovasc Surg 2005;130:1310.

SOURCE CorMatrix Cardiovascular, Inc.