Composition for the delivery of live cells and methods of use

Abstract

The invention relates to an improved method for administering live cells to a patient and compositions useful in the method. The composition comprises live cells and biocompatible, biodegradable polymer microparticles. The cells and microparticles of the cell/microparticle composition can be contacted immediately prior to administration, or can be contacted in culture for a specified period of time prior to administration. In the method of the invention, an effective amount of the cell/microparticle composition is administered to a patient in need thereof by injection to a treatment site of the patient to provide a therapeutic effect in the patient. The therapeutic effect can be, for example, the formation of new tissue at the treatment site, or the production and secretion of a biologically active secretory molecule at the treatment site. The composition comprising lives cells and biocompatible, biodegradable polymer microparticles can be used in a method of generating new tissue in vitro. The method comprises placing the composition in a cell culture chamber under conditions wherein a coherent mass of tissue is formed. In a particular embodiment, the culture chamber is in a specified shape which results in the generation tissue having said shape.

What is claimed is:  
     
         1 . A method of administering live cells to a patient in need thereof comprising 
 injecting into a treatment site of the patient an effective amount of a composition comprising biocompatible, biodegradable polymer microparticles and live cells, wherein said cells provide a therapeutic effect in the patient.    
     
     
         2 . The method of  claim 1  wherein the therapeutic effect comprises the generation of new tissue at the treatment site.  
     
     
         3 . The method of  claim 2  wherein the live cells are selected from cartilage producing cells, organ cells, fibroblasts, osteoblasts, nerve cells, smooth muscle cells, skeletal muscle cells, and Schwann cells.  
     
     
         4 . The method of  claim 2  wherein the cells are chondrocytes.  
     
     
         5 . The method of  claim 4  wherein the new tissue is cartilage tissue.  
     
     
         6 . The method of  claim 5  wherein the treatment site is into the articular space of a joint of the patient.  
     
     
         7 . The method of  claim 1  wherein the therapeutic effect is the secretion of a biologically active secretory molecule.  
     
     
         8 . The method of  claim 7  wherein the biologically active secretory molecule is selected from hormones, cytokines, growth factors, trophic factors, angiogenesis factors, antibodies, blood coagulation factors, lymphokines, enzymes and agonists, precursors, active analogs or active fragments thereof.  
     
     
         9 . The method of  claim 8  wherein the biologically active secretory molecule is the hormone insulin.  
     
     
         10 . The method of  claim 9  wherein the live cells are pancreatic islet cells.  
     
     
         11 . The method of  claim 8  wherein the biologically active secretory molecule is dopamine.  
     
     
         12 . The method of  claim 11  wherein the live cells are selected from PC-12 cells, adrenal chromaffin cells and fetal nigral primordia cells.  
     
     
         13 . The method of  claim 1  wherein the biocompatible, biodegradable polymer of the microparticle is selected from poly(lactides), poly(glycolides), poly(lactide-co-glycolides), poly(lactic acid)s, poly(glycolic acid)s, polycarbonates, polyesteramides, polyanydrides, poly(amino acids), polyorthoesters, poly(dioxanone)s, poly(alkylene alkylate)s, copolymers of polyethylene glycol and polyorthoester, polyurethanes, blends thereof, and copolymers thereof.  
     
     
         14 . The method of  claim 13  wherein the biocompatible, biodegradable polymer is a poly(lactide-co-glycolide).  
     
     
         15 . The method of  claim 1  wherein the composition further comprises a pharmaceutically acceptable carrier.  
     
     
         16 . The method of  claim 1  wherein the composition further comprises a biologically active agent.  
     
     
         17 . The method of  claim 16  wherein the biologically active agent has tissue regeneration inductive properties.  
     
     
         18 . The method of  claim 17  wherein the biologically active agent is a growth factor or differentiating factor.  
     
     
         19 . The method of  claim 18  wherein the growth factor is selected from basic fibroblast growth factor (bFGF), platelet-derived growth factors (PDGF), transforming growth factors (TGF-α, TGF-β), cementum growth factors, epidermal growth factor (EGF), hepatocyte growth factor, heparin binding factor, insulin-like growth factors I or II (IGF-I, IGF-II), erythropoietin, and nerve growth factor (NGF).  
     
     
         20 . The method of  claim 18  wherein the differentiating factor is a morphogenic protein.  
     
     
         21 . The method of  claim 20  wherein the morphogenic protein is selected from OP-1, OP-2, OP-3, BMP2, BMP3, BMP4, BMP5, BMP6 and active fragments and derivatives thereof.  
     
     
         22 . The method of  claim 1  wherein the concentration of cells in the composition is from about 0.5×10 6  cells/mL to about 50×10 6  cells/mL.  
     
     
         23 . A method of generating new cartilage tissue in a patient in need thereof comprising administering by injection to a treatment site of the patient a composition comprising live chondrocytes and biocompatible, biodegradable polymer microparticles.  
     
     
         24 . The method of  claim 23  wherein the biocompatible, biodegradable polymer of the microparticle is selected from poly(lactides), poly(glycolides), poly(lactide-co-glycolides), poly(lactic acid)s, poly(glycolic acid)s, polycarbonates, polyesteramides, polyanydrides, poly(amino acids), polyorthoesters, poly(dioxanone)s, poly(alkylene alkylate)s, copolymers of polyethylene glycol and polyorthoester, polyurethanes, blends thereof, and copolymers thereof.  
     
     
         25 . The method of  claim 24  wherein the biocompatible, biodegradable polymer is a poly(lactide-co-glycolide).  
     
     
         26 . The method of  claim 23  wherein the composition further comprises a pharmaceutically acceptable carrier.  
     
     
         27 . The method of  claim 23  wherein the composition further comprises a biologically active agent.  
     
     
         28 . The method of  claim 27  wherein the biologically active agent has tissue regeneration inductive properties.  
     
     
         29 . The method of  claim 28  wherein the biologically active agent is a growth factor or differentiating factor.  
     
     
         30 . The method of  claim 29  wherein the growth factor is selected from basic fibroblast growth factor (bFGF), platelet-derived growth factors (PDGF), transforming growth factors (TGF-α, TGF-β), cementum growth factors, epidermal growth factor (EGF), hepatocyte growth factor, heparin binding factor, insulin-like growth factors I or II (IGF-I, IGF-II), erythropoietin, and nerve growth factor (NGF).  
     
     
         31 . The method of  claim 29  wherein the differentiating factor is a morphogenic protein.  
     
     
         32 . The method of  claim 31  wherein the morphogenic protein is selected from OP-1, OP-2, OP-3, BMP2, BMP3, BMP4, BMP5, BMP6 and active fragments and derivatives thereof.  
     
     
         33 . The method of  claim 23  wherein the concentration of cells in the composition is from about 0.5×10 6  cells/mL to about 50×10 6  cells/mL.  
     
     
         34 . A method of generating new internal organ tissue in a patient in need thereof comprising administering by injection to a treatment site of the patient a composition comprising live internal organ cells and biocompatible, biodegradable polymer microparticles.  
     
     
         35 . The method of  claim 34  wherein the treatment site is an organ of the patient, wherein the organ and administered cells are of the same tissue type.  
     
     
         36 . The method of  claim 35  wherein the live internal organ cells are selected from heart cells, lung cells, kidney cells, liver cells, pancreatic cells and brain cells.  
     
     
         37 . A method for treating diabetes in a patient in need of treatment comprising administering to the patient by injection into a treatment site an effective amount of a composition comprising biocompatible, biodegradable polymer microparticles and live pancreatic islet cell, wherein said cells secrete insulin.  
     
     
         38 . The method of  claim 37  wherein the treatment site is the pancreas of the patient.  
     
     
         39 . A method of generating new tissue comprising placing a composition comprising live cells and a biocompatible, biodegradable polymer microparticles and culturing said cells under conditions to provide a coherent mass of tissue.  
     
     
         40 . The method of  claim 39  wherein said cells are cultured in a cell culture chamber having a specified anatomical shape resulting in a coherent tissue mass of the specified shape.  
     
     
         41 . The method of  claim 40  wherein the live cells are chondrocytes.  
     
     
         42 . The method of  claim 41  wherein the tissue is cartilage.  
     
     
         43 . The method of  claim 39  wherein the biocompatible, biodegradable polymer of the microparticle is selected from poly(lactides), poly(glycolides), poly(lactide-co-glycolides), poly(lactic acid)s, poly(glycolic acid)s, polycarbonates, polyesteramides, polyanydrides, poly(amino acids), polyorthoesters, poly(dioxanone)s, poly(alkylene alkylate)s, copolymers of polyethylene glycol and polyorthoester, polyurethanes, blends thereof, and copolymers thereof.  
     
     
         44 . The method of  claim 43  wherein the biocompatible, biodegradable polymer is a poly(lactide-co-glycolide).  
     
     
         45 . A composition comprising biocompatible, biodegradable polymer microparticles and live cells.  
     
     
         46 . The composition of  claim 45  wherein the biocompatible, biodegradable polymer of the microparticle is selected from poly(lactides), poly(glycolides), poly(lactide-co-glycolides), poly(lactic acid)s, poly(glycolic acid)s, polycarbonates, polyesteramides, polyanydrides, poly(amino acids), polyorthoesters, poly(dioxanone)s, poly(alkylene alkylate)s, copolymers of polyethylene glycol and polyorthoester, polyurethanes, blends thereof, and copolymers thereof.  
     
     
         47 . The composition of  claim 46  wherein the biocompatible, biodegradable polymer is a poly(lactide-co-glycolide).  
     
     
         48 . The composition of  claim 45  wherein the live cells generate tissue.  
     
     
         49 . The composition of  claim 48  wherein the live cells are chondrocytes.  
     
     
         50 . The composition of  claim 48  wherein the live cells are hepatocytes.  
     
     
         51 . The composition of  claim 45  wherein the live cells secrete a biologically active secretory molecule.  
     
     
         52 . The composition of  claim 51  wherein the live cells are pancreatic islet cells.  
     
     
         53 . The composition of  claim 51  wherein the live cells are dopaminergic cells.  
     
     
         54 . The composition of  claim 53  wherein the cells are selected from PC-12 cells, adrenal chromaffin cells and fetal nigral primordia cell.  
     
     
         55 . The composition of  claim 45  wherein the composition further comprises a pharmaceutically acceptable carrier.  
     
     
         56 . The composition of  claim 45  wherein the composition further comprises a biologically active agent.  
     
     
         57 . The composition of  claim 56  wherein the biologically active agent has tissue regeneration inductive properties.  
     
     
         58 . The composition of  claim 57  wherein the biologically active agent is a growth factor or differentiating factor.  
     
     
         59 . The composition of  claim 58  wherein the growth factor is selected from basic fibroblast growth factor (Bfgf), platelet-derived growth factors (PDGF), transforming growth factors (TGF-α, TGF-β), cementum growth factors, epidermal growth factor (EGF), hepatocyte growth factor, heparin binding factor, insulin-like growth factors I or II (IGF-I, IGF-II), erythropoietin, and nerve growth factor (NGF).  
     
     
         60 . The composition of  claim 58  wherein the differentiating factor is a morphogenic protein.  
     
     
         61 . The composition of claim  60  wherein the morphogenic protein is selected from OP-1, OP-2, OP-3, BMP2, BMP3, BMP4, BMP5, BMP6 and active fragments and derivatives thereof.  
     
     
         62 . The composition of  claim 45  wherein the concentration of cells in the composition is from about 0.5×10 6  cells/mL to about 50×10 6  cells/mL.