Methods and devices for promoting endothelial morphogenesis
In one aspect the present invention provides methods for promoting endothelial morphogenesis. The methods of this aspect of the invention include the step of providing to one or more endothelial cells an amount of an osteoprotegerin sufficient to promote endothelial morphogenesis. The methods of this aspect of the invention can be practiced in vivo or in vitro. In another aspect, the present invention provides implantable medical devices that each include: (a) a device body; and (b) a layer attached to a surface of the device body, the layer comprising a molecule selected from the group consisting of osteoprotegerin and a nucleic acid molecule encoding osteoprotegerin, wherein the device is adapted to be completely or partially implanted into an animal body. The implanted medical device thus promotes the growth of blood vessels in the surrounding tissue, thereby reducing or preventing the formation of a collagenous capsule around the implanted medical device.
1. A method for promoting endothelial morphogenesis in vitro, said method comprising the step of providing to endothelial cells cultured on a porous matrix or scaffold that supports tissue growth in vitro an amount of an osteoprotegerin sufficient to promote endothelial morphogenesis.
2. The method of claim 1 , wherein the osteoprotegerin is at least 70% identical to the osteoprotegerin consisting of the amino acid sequence set forth in SEQ ID NO: 2.
3. The method of claim 1 , wherein the osteoprotegerin is at least 80% identical to the osteoprotegerin consisting of the amino acid sequence set forth in SEQ ID NO: 2.
4. The method of claim 1 , wherein the osteoprotegerin is at least 90% identical to the osteoprotegerin consisting of the amino acid sequence set forth in SEQ ID NO: 2.
5. The method of claim 1 , wherein the endothelial cells are cultured in a liquid medium that comprises the osteoprotegerin.
6. The method of claim 1 , wherein the endothelial morphogenesis is formation of capillaries.
7. The method of claim 1 , wherein the endothelial morphogenesis is formation of an endothelial lining in a blood vessel.
8. The method of claim 7 , wherein the endothelial lining is formed in an artificial blood vessel.
9. The method of claim 7 , wherein the endothelial lining is formed in a natural blood vessel.