Implantable bioreactor for delivery of paracrine factors

Abstract

An implantable bioreactor containing a barrier which is designed to allow the release of cell-derived biomolecules, but restricts the entry of immunologic and other cells, or the egress of the cells contained within the bioreactor. Two broad classes of implantable bioreactors are envisioned, encompassing devices for both systemic delivery of the bio-products and local delivery at the target tissue. Bioreactors of both classes can be implanted via surgery, through percutaneous techniques, or other techniques which effect implantation.

1 . An intravascular implantable bioreactor, comprising:
 a pouch; and   cells enclosed within the pouch, said cells being capable of producing paracrine factors,   wherein the pouch is collapsible and expandable to be intravascularly implantable, wherein the pouch is semipermeable such that it provides containment of the cells,   preventing the egress of the cells while further providing a barrier that shields the cells from immunological attack, and   wherein the pouch comprises multiple pores having a diameter of at least about 0.1 μm, such that the pores are capable of releasing out of the pouch paracrine factors that enhance recovery of injured tissue.   
     
     
         2 . The intravascular implantable bioreactor of  claim 1 , wherein the cells are stem cells and the injured tissue is myocardium. 
     
     
         3 . The intravascular implantable bioreactor of  claim 2 , wherein the stem cells are selected from the group consisting of embryonic stem cells, mesenchymal stem cells, whole bone marrow stem cells, adipose-derived stem cells, myocardial derived stem cells and endothelial progenitor stem cells, with and/or without genetic alterations. 
     
     
         4 . The intravascular implantable bioreactor of  claim 1 , wherein said pouch is composed of cellulosic and/or synthetic materials. 
     
     
         5 . The intravascular implantable bioreactor of  claim 1 , wherein the pouch is mounted on a wire, a catheter or is part of another implantable device. 
     
     
         6 . The intravascular implantable bioreactor of  claim 1 , wherein the bioreactor is adhered to a medical device. 
     
     
         7 . The intravascular implantable bioreactor of  claim 6 , wherein the medical device is a stent, intra-aortic balloon pump, ventricular assist device, prosthetic valve, prosthetic valve clip, prosthetic valve ring, thrombus filter, pacemaker, defibrillator, pacemaker or defibrillator wire, septal occluder, atrial appendage device, pulmonary artery catheter, venous catheter or arterial catheter. 
     
     
         8 . The intravascular implantable bioreactor of  claim 1 , wherein said pouch comprises surface undulations and crevices. 
     
     
         9 . The intravascular implantable bioreactor of  claim 2 , wherein said pouch defines an interior surface, said interior surface being coated with molecules that enhance stem cell attachment and function. 
     
     
         10 . The intravascular implantable bioreactor of  claim 1 , wherein said pouch defines an exterior surface, said exterior surface being coated with anticoagulants that hinder thrombosis. 
     
     
         11 . The intravascular implantable bioreactor of  claim 1 , wherein said pouch defines a port configured to be accessible to permit a containment space defined by said pouch to be at least one of emptied, filled or refilled. 
     
     
         12 . The intravascular implantable bioreactor of  claim 11 , further comprising a catheter having a distal end and a proximal end, said distal end of said catheter being attached to said pouch through said port; and
 wherein said catheter is at least partially intravascularly implantable such that said distal end of said catheter is intravascularly implantable while said proximal end of said catheter is adapted to extend exterior to a patient's body while in use.   
     
     
         13 . An intravascular implantable bioreactor comprising a pouch that is collapsible and expandable to be intravascularly implantable, said pouch defining a housing to enclose cells therein for cells that are capable of producing paracrine factors,
 wherein the pouch is semipermeable such that it provides containment of cells while further providing a barrier that shields the cells from immunological attack, and   wherein the pouch comprises multiple pores having a diameter of at least about 0.1 μm, such that the pores are capable of releasing out of the pouch paracrine factors that enhance recovery of injured tissue.   
     
     
         14 . The intravascular implantable bioreactor of  claim 13 , wherein said pouch comprises surface undulations and crevices. 
     
     
         15 . The intravascular implantable bioreactor of  claim 13 , wherein said pouch defines an interior surface, said interior surface being coated with molecules that enhance stem cell attachment and function. 
     
     
         16 . The intravascular implantable bioreactor of  claim 13 , wherein said pouch defines an exterior surface, said exterior surface being coated with anticoagulants that hinder thrombosis. 
     
     
         17 . The intravascular implantable bioreactor of  claim 13 , wherein said pouch defines a port configured to be accessible to permit a containment space defined by said pouch to be at least one of emptied, filled or refilled. 
     
     
         18 . The intravascular implantable bioreactor of  claim 17 , further comprising a catheter having a distal end and a proximal end;
 said distal end of said catheter being attached to said pouch through said port; and   wherein said catheter is at least partially intravascularly implantable such that said distal end of said catheter intravascularly implantable while said proximal end of said catheter is adapted to extend exterior to a patient's body while in use.   
     
     
         19 . The intravascular implantable bioreactor of  claim 1 , wherein said pouch comprises surface undulations and crevices, and wherein the area enclosed by the pouch contains a matrix gel;
 wherein said pouch defines an exterior surface;   said exterior surface being coated with anticoagulants that hinder thrombosis;   wherein said pouch defines a port configured to be accessible to permit a containment space defined by said pouch to be at least one of emptied, filled or refilled; and   further comprising a catheter having a distal end and a proximal end, said distal end of said catheter being attached to said pouch through said port, wherein said catheter is at least partially intravascularly implantable such that said distal end of said catheter is intravascularly implantable while said proximal end of said catheter is adapted to extend exterior to a patient's body while in use.   
     
     
         20 . The intravascular implantable bioreactor of  claim 6 , wherein said pouch comprises surface undulations and crevices. 
     
     
         21 . The intravascular implantable bioreactor of  claim 6 , wherein said pouch defines an interior surface, said interior surface being coated with molecules that enhance stem cell attachment and function. 
     
     
         22 . The intravascular implantable bioreactor of  claim 6 , wherein said pouch defines an exterior surface, said exterior surface being coated with anticoagulants that hinder thrombosis. 
     
     
         23 . The intravascular implantable bioreactor of  claim 6 , wherein said pouch defines a port configured to be accessible to permit a containment space defined by said pouch to be at least one of emptied, filled or refilled. 
     
     
         24 . The intravascular implantable bioreactor of  claim 1 , wherein said pouch comprises polytetrafluoroethylene. 
     
     
         25 . The intravascular implantable bioreactor of  claim 1 , wherein said pouch comprises derivatives of polytetrafluoroethylene. 
     
     
         26 . The intravascular implantable bioreactor of  claim 1 , wherein the multiple pores have a diameter of from about 0.1 μm to about 15 μm. 
     
     
         27 . The intravascular implantable bioreactor of  claim 26 , wherein the multiple pores have a diameter of from about 1 μm to about 3 μm. 
     
     
         28 . The intravascular implantable bioreactor of  claim 1 , wherein the multiple pores are present in a density of from about 100,000 to about 10,000,000 pores per cm 2 . 
     
     
         29 . The intravascular implantable bioreactor of  claim 1 , wherein the multiple pores were introduced into the pouch by etching. 
     
     
         30 . The intravascular implantable bioreactor of  claim 13 , wherein the multiple pores have a diameter of from about 0.1 μm to about 15 μm. 
     
     
         31 . The intravascular implantable bioreactor of  claim 30 , wherein the multiple pores have a diameter of from about 1 μm to about 3 μm. 
     
     
         32 . The intravascular implantable bioreactor of  claim 13 , wherein the multiple pores are present in a density of from about 100,000 to about 10,000,000 pores per cm 2 . 
     
     
         33 . The intravascular implantable bioreactor of  claim 13 , wherein the multiple pores were introduced into the pouch by etching.