Cell seeded expandable body

Abstract

Devices, systems and methods for treating medical conditions using cell therapy via body lumens. Localized delivery is achieved with the use of a stent-like expandable body seeded with cells. The expandable body is expanded to contact at least a portion of the inner walls of the body lumen and the cells, cellular products and/or other therapeutic agents are delivered to the surrounding tissue. The therapeutic benefit provided is dependent on the type of cells used and the features of the expandable body.

1 . A system for treating a patient comprising: 
 an expandable body having a proximal end, a distal end, a longitudinal axis therebetween, and at least one microstructure having an attached end attached to the body and a free end which is projectable radially outwardly from the expandable body; and    a plurality of cells disposed on at least one surface of the expandable body.    
     
     
         2 . A system as in  claim 1 , wherein the at least one surface is located on an outer surface of the expandable body.  
     
     
         3 . A system as in  claim 1 , wherein the surface includes pores.  
     
     
         4 . A system as in  claim 3 , wherein the pores are sized to allow positioning of the cells within the pores.  
     
     
         5 . A system as in  claim 3 , wherein the surface provides controlled time dependent release of a substance over time.  
     
     
         6 . A system as in  claim 2 , wherein the surface comprises a nanoporous metallic coating wherein the coating has a morphology that provides controlled time dependent release of a substance over time.  
     
     
         7 . A system as in  claim 6 , wherein the substance promotes cell adherence and/or cell growth.  
     
     
         8 . A system as in  claim 7 , wherein the substance comprises a member of the TGF β  family.  
     
     
         9 . A system as in  claim 8 , wherein the substance comprises TGF β1 .  
     
     
         10 . A system as in  claim 6 , wherein the substance augments growth of endothelial cells and/or smooth muscle cells.  
     
     
         11 . A system as in  claim 10 , wherein the substance comprises VEGF, bFGF, PLGF, PDGF, or a combination of these.  
     
     
         12 . A system as in claims  5  or  6 , wherein at least some of the plurality of cells contain a therapeutic gene and wherein the substance comprises an agent that controls the activity of the therapeutic gene contained with the cells.  
     
     
         13 . A system as in  claim 1 , further comprising a substance on the surface which improves adhesion of the plurality of cells to the surface.  
     
     
         14 . A system as in  claim 13 , wherein the substance comprises polymer substrates, biocompatible proteins, growth factors, extracellular matrix components or a combination of any of these.  
     
     
         15 . A system as in  claim 1 , wherein the at least one surface is located on an internal lumen within the at least one microstructure.  
     
     
         16 . A system as in  claim 15 , wherein the plurality of cells comprise cells which are non-autologous to the patient, and wherein the non-autologous cells are disposed within the at least one microstructure so that the non-autologous cells are immunologically isolated from the patient's immune system.  
     
     
         17 . A system as in  claim 1 , wherein expansion of the body creates forces which deploy the at least one microstructure from an undeployed position wherein the free end is substantially aligned with an outer surface of the expandable body to a deployed position wherein the free end projects radially outwardly from the expandable body.  
     
     
         18 . A system as in  claim 1 , wherein the plurality of cells comprise smooth muscle cells, autologous smooth muscle cells, non-autologous smooth muscle cells, stem cell derived smooth muscle cells, or smooth muscle progenitor cells.  
     
     
         19 . A system as in  claim 1 , wherein the plurality of cells comprise endothelial cells.  
     
     
         20 . A system as in  claim 1 , wherein the plurality of cells comprise epithelial cells.  
     
     
         21 . A system as in  claim 1 , wherein the plurality of cells comprise stem cell derived cell populations.  
     
     
         22 . A system as in  claim 1 , wherein the plurality of cells comprise embryonic stem cells and/or derivatives of embryonic stem cells.  
     
     
         23 . A system as in  claim 1 , wherein the plurality of cells comprise pancreatic beta cells, myofibroblasts, cardiac myocytes, skeletal muscle satellite cells, dendritic cells, multi-potential somatic stem cells, derivatives of multi-potential somatic stem cells, neuronal cells, glial cells, hepatocytes, or endocrine cells.  
     
     
         24 . A system as in  claim 1 , wherein the plurality of cells are genetically modified.  
     
     
         25 . A system as in  claim 24 , wherein the plurality of cells are genetically modified to over-express endothelial nitric oxide synthase, inducible nitric oxide synthase, TGF β1 , IL-4, IL-10, IL-13, PDGF, PLGF, VEGF, or a combination of these.  
     
     
         26 . A system as in  claim 1 , wherein the expandable body is sized for positioning within a body lumen having a wall.  
     
     
         27 . A system as in  claim 26 , wherein the free end is projectable radially outwardly from the expandable body a distance sufficient to penetrate the wall of the body lumen.  
     
     
         28 . A system as in  claim 26 , wherein the body lumen comprises a blood vessel.  
     
     
         29 . A system as in  claim 26 , wherein the body lumen is disposed within the gastro-intestinal tract, the pulmonary system, the urinary system or the reproductive system.  
     
     
         30 . A system for treating a patient comprising: 
 an expandable body having a proximal end, a distal end, a longitudinal axis therebetween, and at least one microstructure having an attached end attached to the body and a free end in an undeployed position along the expandable body,    expansion of the body creating forces which deploy the at least one microstructure from the undeployed position to a deployed position wherein the free end projects radially outwardly from the expandable body; and    a plurality of genetically modified cells disposed on at least one surface of the expandable body.    
     
     
         31 . A system as in  claim 30 , wherein the plurality of genetically modified cells are genetically modified to over-express a therapeutic gene.  
     
     
         32 . A system as in  claim 31 , wherein the therapeutic gene comprises endothelial nitric oxide synthase, inducible nitric oxide synthase, TGF β1 , IL-4, IL-10, IL-13, PDGF, PLGF, VEGF or a combination of these.  
     
     
         33 . A system as in  claim 30 , wherein the plurality of genetically modified cells comprises genetically modified autologous smooth muscle cells, stem cell derived smooth muscle cells, smooth muscle progenitor cells or a combination of any of these.  
     
     
         34 . A system as in  claim 30 , wherein the plurality of cells comprise endothelial cells.  
     
     
         35 . A system as in  claim 30 , wherein the plurality of cells comprise epithelial cells.  
     
     
         36 . A system as in  claim 30 , wherein the plurality of cells comprise embryonic stem cells and/or derivatives of embryonic stem cells.  
     
     
         37 . A system as in  claim 30 , wherein the plurality of cells comprise pancreatic beta cells, myofibroblasts, cardiac myocytes, skeletal muscle satellite cells, dendritic cells, multi-potential somatic stem cells, derivatives of multi-potential somatic stem cells, neuronal cells, glial cells, hepatocytes, or endocrine cells.  
     
     
         38 . A system as in  claim 30 , wherein the at least one microstructure has a directional axis between the free end and the attached end, and wherein the directional axis extends along the longitudinal axis while the at least one microstructure is in the undeployed position.  
     
     
         39 . A system as in  claim 30 , wherein the at least one microstructure has a directional axis between the free end and the attached end, and wherein the directional axis extends across the longitudinal axis while the at least one microstructure is in the undeployed position.  
     
     
         40 . A system as in  claim 30 , wherein the free end has a pointed shape.  
     
     
         41 . A system as in  claim 40 , wherein the at least one microstructure has an internal lumen therein and wherein the at least one surface is located on the internal lumen.  
     
     
         42 . A system as in  claim 41 , wherein the expandable body comprises an endoluminal stent sized for positioning within a vascular lumen having a vascular lumen wall.  
     
     
         43 . A system as in  claim 42 , wherein the vascular lumen wall includes a medial layer and the at least one microstructure are sized to dissect the vascular lumen wall during expansion of the expandable body for delivery of the plurality of genetically modified cells to at least the medial layer.  
     
     
         44 . A system as in  claim 41 , wherein the expandable body comprises an endoluminal stent sized for positioning within a body lumen disposed within the gastro-intestinal tract, the pulmonary system, the urinary system or the reproductive system.  
     
     
         45 . A system for treating a patient comprising: 
 a stent having a proximal end, a distal end, a longitudinal axis therebetween, the stent sized for positioning within a body lumen; and    a plurality of progenitor cells of a desired cell type disposed on at least one surface of the stent for delivery to the body lumen, the progenitor cells derived by a method comprising the steps of    providing a population of cells comprising totipotent or pluripotent cells,    transfecting the population of cells with a nucleic acid sequence comprising a desired cell type specific promoter/enhancer operably linked to a marker,    inducing the population of cells to become cells of the desired cell type, and    identifying the progenitor cells based on the expression of the marker.    
     
     
         46 . A system as in  claim 45 , wherein the desired cell type comprises epithelial cells.  
     
     
         47 . A system as in  claim 45 , wherein the desired cell type comprises endothelial cells.  
     
     
         48 . A system as in  claim 45 , wherein the desired cell type comprises smooth muscle cells.  
     
     
         49 . A system as in  claim 45 , wherein the surface comprises a nanoporous metallic coating.  
     
     
         50 . A system as in  claim 49 , wherein the coating has a morphology that provides controlled time dependent release of a substance.  
     
     
         51 . A system as in  claim 50 , wherein the substance promotes cell adherence and/or cell growth.  
     
     
         52 . A system as in  claim 51 , wherein the substance comprises a substrate in the TGF β  family.  
     
     
         53 . A system as in  claim 50 , wherein the substance augments growth of endothelial cells and/or smooth muscle cells.  
     
     
         54 . A system as in  claim 53 , wherein the substance comprises VEGF, bFGF, PLGF, PDGF, or a combination of these.  
     
     
         55 . A system for treating a patient comprising: 
 a stent having a proximal end, a distal end, a longitudinal axis therebetween, the stent sized for positioning within a body lumen; and    a plurality of smooth muscle progenitor cells disposed on at least one surface of the stent for delivery to the body lumen, the progenitor cells derived by a method comprising the steps of    providing a population of cells comprising totipotent or pluripotent cells,    transfecting the population of cells with a nucleic acid sequence comprising a smooth muscle cell specific promoter/enhancer operably linked to a marker,    inducing the population of cells to become smooth muscle cells and    identifying the smooth muscle progenitor cells based on the expression of the marker.    
     
     
         56 . A system as in  claim 55 , wherein the at least one surface is located on an outer surface of the stent.  
     
     
         57 . A system as in  claim 55 , wherein the at least one surface includes pores.  
     
     
         58 . A system as in  claim 55 , further comprising a substance on the surface to improve adhesion of the plurality of cells to the surface.  
     
     
         59 . A system as in  claim 58 , wherein the substance comprises polymer substrates, biocompatible proteins, growth factors, extracellular matrix components or a combination of any of these.  
     
     
         60 . A system as in  claim 58 , wherein the at least one surface comprises a nanoporous metallic coating.  
     
     
         61 . A system as in  claim 60 , wherein the coating has a morphology that provides controlled time dependent release of the substance.  
     
     
         62 . A system as in  claim 61 , wherein the substance promotes cell adherence and/or cell growth.  
     
     
         63 . A system as in  claim 62 , wherein the substance comprises a substrate in the TGF β  family.  
     
     
         64 . A system as in  claim 61 , wherein the substance augments growth of endothelial cells and/or smooth muscle cells.  
     
     
         65 . A system as in  claim 64 , wherein the substance comprises VEGF, bFGF, PLGF, PDGF, or a combination of these.  
     
     
         66 . A system for repair of an aneurysm in a blood vessel of a patient comprising: 
 a tube having a first end, a second end and a wall extending between the first and second ends, the tube shaped to be disposed at least partially within the aneurysm;    at least one expandable body attached to the tube wall including at least one microstructure having an attached end attached to the body and a free end in an undeployed position, wherein expansion of the at least one expandable body creates forces which deploy the at least one microstructure from the undeployed position to a deployed position wherein the free end of the at least one microstructure projects radially outwardly from the tube; and    a plurality of cells disposed on at least one surface of the at least one expandable body.    
     
     
         67 . A system as in  claim 66 , wherein the at least one surface is located on an internal lumen within the at least one microstructure.  
     
     
         68 . A system as in  claim 66 , wherein the at least one surface is located on an outer surface of the expandable body.  
     
     
         69 . A system as in  claim 66 , wherein the surface includes pores.  
     
     
         70 . A system as in  claim 66 , wherein the plurality of cells are selected from the group consisting of smooth muscle cells, autologous smooth muscle cells, stem cell derived smooth muscle cells, and smooth muscle progenitor cells.  
     
     
         71 . A system as in  claim 66 , further comprising a coating on the surface to improve adhesion of the plurality of cells to the surface.  
     
     
         72 . A system as in  claim 71 , wherein the coating includes a nanoporous metallic coating.  
     
     
         73 . A system as in  claim 74 , wherein the substance comprises polymer substrates, biocompatible proteins, growth factors or a combination of any of these.  
     
     
         74 . An apparatus as in  claim 66 , wherein the at least one expandable body is attached to an exterior surface of the tube wall.  
     
     
         75 . An apparatus as in  claim 66 , wherein the at least one expandable body is embedded within the tube wall.  
     
     
         76 . An apparatus as in  claim 66 , wherein the at least one expandable body is attached to an interior surface of the tube wall.  
     
     
         77 . An apparatus as in  claim 66 , wherein the at least one microstructure projects radially outwardly from the tube a distance sufficient to penetrate the blood vessel to deliver the plurality of cells to the blood vessel.  
     
     
         78 . An apparatus as in  claim 66 , wherein the blood vessel comprises a segment of an aorta having two iliac arteries therewith at an aortic bifurcation, and wherein the tube further comprises an opening between the first end and the second end to align with one of the iliac arteries.  
     
     
         79 . A system for treating a patient comprising: 
 an expandable body having a proximal end, a distal end, a longitudinal axis therebetween; and    a plurality of cells disposed on at least one surface of the expandable body.    
     
     
         80 . A system as in  claim 79 , wherein the expandable body includes at least one surface having a coating which augments cell attachment, augments cell growth and/or releases a therapeutic substance.  
     
     
         81 . A system as in  claim 80 , wherein the coating comprises a nanoporous metallic coating.  
     
     
         82 . A system as in  claim 81 , wherein the nanoporous metalling coating has a morphology that provides controlled time dependent release of the therapeutic substance.  
     
     
         83 . A system as in  claim 82 , wherein the substance comprises a member of the TGF β  family.  
     
     
         84 . A system as in  claim 82 , wherein the substance comprises VEGF, bFGF, PLGF, or a combination of these.  
     
     
         85 . A system as in  claim 79 , wherein the plurality of cells comprise smooth muscle cells, autologous muscle cells, stem cell derived smooth muscle cells, or smooth muscle progenitor cells.  
     
     
         86 . A system as in  claim 85 , wherein the plurality of cells are genetically modified.  
     
     
         87 . A system for treating a patient comprising: 
 an expandable body having a proximal end, a distal end, a longitudinal axis therebetween, and at least one microstructure having an attached end attached to the body and a free end which is projectable radially outwardly from the expandable body to penetrate a body lumen of the patient; and    a plurality of cells disposed on at least one surface of the expandable body so that the cells are immunoisolated from the body lumen of the patient.    
     
     
         88 . A system as in  claim 87 , wherein the at least one surface is located on an internal lumen within the at least one microstructure.  
     
     
         89 . A system as in  claim 88 , wherein the cells produce a therapeutic agent, and wherein the microstructures are configured to deliver the therapeutic agent to the body lumen without the cells contacting the body lumen.  
     
     
         90 . A system as in  claim 87 , further comprising a nanoporous membrane incorporated into the microstructures.  
     
     
         91 . A system as in  claim 90 , wherein the cells produce a cellular products, and wherein the membrane permits transport of the cellular products out of the microstructures and into the body lumen.  
     
     
         92 . A system as in  claim 90 , wherein the membrane permits in-flow of nutrients to the cells.  
     
     
         93 . A system as in  claim 87 , wherein the cells comprise embryonic stem cells.