Compositions for regenerating defective or absent myocardium

Abstract

Compositions of the invention for regenerating defective or absent myocardium comprise an emulsified or injectable extracellular matrix composition. The composition can also have an extracellular matrix scaffold component of any formulation, then including also added cells, proteins, or other components to optimize the regenerative process and restore cardiac function. Methods for regenerating defective or absent myocardium apply a composition to a site of myocardium in need of regeneration using a delivery mode appropriate for the particular formulation.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS [0001] The present application is a divisional of parent application Ser. No. 11 / 182,551 filed Jul. 15, 2005.FIELD OF THE INVENTION [0002] The invention relates to tissue engineering generally, and more specifically to compositions and methods for regenerating defective or absent myocardium. BACKGROUND OF THE INVENTION [0003] Heart failure occurs in nearly 5 million people a year in the U.S. alone at a combined cost of about $40 billion annually for hospitalization and treatment of these patients. The results of all the effort and cost are disappointing with a 75% five year mortality rate for the heart failure victims. Treatments for chronic heart failure include medical management with pharmaceutical drugs, diet and exercise, transplantation for a few lucky recipients, and mechanical assist devices, which are costly and risk failure and infection. Thus the landscape for cardiac treatment is turning in recent years to transplantation of tissu...

AI Technical Summary

Benefits of technology

[0017] d) a nutrient, a sugar, a fat, a lipid, an amino acid, a nucleic acid, a ribo-nucleic acid, an organic molecule, an inorganic molecule, a small molecule, a drug, or a bioactive molecule.

[0018] The emulsion comprises mammalian extracellular matrix selected from the group consisting of small intestine submucosa (SIS), urinary bladder submucosa (UBS), urinary basement membrane (UBM), liver basement membrane (LBM), stomach submucosa (SS), collagen from animal sources, collagen from plant sources, synthesized extracellular matrix in cultures from cells (Matrigel™), dermal extracellular matrix material, subcutaneous extracellular matrix material, large intestine extracellular matrix material, placental extracellular matrix material, ornamentum extracellular matrix material, heart extracellular matrix material, and lung extracellular matrix material.

Problems solved by technology

The results of all the effort and cost are disappointing with a 75% five year mortality rate for the heart failure victims.

Treatments for chronic heart failure include medical management with pharmaceutical drugs, diet and exercise, transplantation for a few lucky recipients, and mechanical assist devices, which are costly and risk failure and infection.

Medical researchers have transplanted human hematopoetic stem cells, mesenchymal stem cells, endothelial precursor cells, cardiac stem cells, and skeletal myoblasts or bone marrow cells to the myocardium, with however little or mixed success in satisfactory regeneration of the myocardium.

As yet, the experiments to prove these theories have not worked sufficiently to be attempted in humans.

Meanwhile, typical structural abnormalities or damage to the heart that would lend itself to tissue regenerative therapies, were they available, include atrial septal defects, ventricular septal defects, right ventricular out flow stenosis, ventricular aneurysms, ventricular infarcts, ischemia in the myocardium, infarcted myocardium, conduction defects, conditions of aneurysmic myocardium, ruptured myocardium, and congenitally defective myocardium, and these defective conditions remain untreated in humans by any current tissue regenerative techniques.

Although tissue regeneration has been accomplished by transplantation in mammalian tissues such as the endocranium, the esophagus, blood vessels, lower urinary tract structures, and musculotendinous tissues, heart tissue regeneration by foreign tissue explant has remained a challenge.

One problem exists in the preparation of extracellular scaffolds in that they must be non-immunogenic and thus acellular before implantation.

Getting rid of the cells in the matrix may also inadvertently strip the scaffold of key bioactive proteins.

No experimentation has been conducted to date on regenerating mammalian myocardium using an emulsified or injectable extracellular matrix formulation.

The disadvantage of using intact, non-emulsified extracellular matrix compositions such as patches or strips is that placement of the material requires open surgery, with its coordinate risk of infection, challenge of access to the site, and longer recovery for the patient post-procedure.

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