Methods for using a three-dimensional stromal tissue to promote angiogenesis

Abstract

The present invention relates to a method for promoting blood vessel formation in tissues and organs. In particular, the method relates to implantation or attachment of an engineered three-dimensional stromal tissue to promote endothelialization and angiogenesis in the heart and related tissues. The three-dimensional stromal tissue of the present invention may be used in a variety of applications including, but not limited to, promoting repair of and regeneration of damaged cardiac muscle, promoting vascularization and healing during cardiac surgery, promoting blood vessel formation at anastomosis sites, and promoting vascularization and repair of damaged skeletal muscle, smooth muscle or connective tissue.

Description

1. INTRODUCTION[0001] The present invention relates to a method for promoting method relates to implantation or attachment of a three-dimensional stromal tissue to promote endothelialization and vascularization in the heart and related tissues.2. BACKGROUND OF THE INVENTION[0002] Coronary heart disease is the single leading cause of death in America today (American Heart Association's "1999 Heart and Stroke Statistical Update"). This disease, as with various other cardiovascular disorders, is characterized by the narrowing of arteries and inadequate blood flow to critical tissues.[0003] Currently used clinical methods for improving blood flow in a diseased or otherwise damaged heart involve invasive surgical techniques such as coronary by-pass surgery, angioplasty, and endarterectomy. Such procedures naturally involve high-degrees of inherent risk during and after surgery, and often only provide a temporary remedy to cardiac ischemia.[0004] In an effort to improve the prognosis of s...

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Benefits of technology

[0009] The invention is based in part on the discovery that three-dimensional stromal tissue constructs, when implanted in the wound bed of patients with diabetic foot ulcers, are capable of inducing rapid endothelialization and vascularization, resulting in new capillary formation and reduced inflammation in the wounded tissue.

[0010] The three-dimensional stromal tissue implants secrete a variety of growth factors critical to tissue regeneration and angiogenesis, most notably vascular endothelial growth factor, or VEGF (Table II). The invention encompasses the application of the three-dimensional stromal tissue to damaged tissues, such as damaged cardiac muscle, to induce a new local blood supply to the area and support rapid tissue remodeling.

Problems solved by technology

Such procedures naturally involve high-degrees of inherent risk during and after surgery, and often only provide a temporary remedy to cardiac ischemia.

However, such pumps only act as temporary assist devices during surgery, they cannot be used as a form of treatment for the cardiac condition.

However, such attempts have been largely unsuccessful.

However, such gene therapy techniques utilizing retroviral vectors present certain inherent risks and safety concerns.

In addition, gene therapy-type approaches present a number of unresolved, problematic technical hurdles such as low transfection levels for recipient cells, construct instability and long-term expression of the desired gene product from the transfected cells.

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