Composition for the delivery of live cells and methods of use thereof

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 therapeutic effect resulting from injection of the cell/microparticle composition into a treatment site, is determined by the type of cell present in the composition. The composition comprising lives cells and biocompatible, biodegradable polymer microparticles can further comprise a biologically active agent. In a preferred embodiment, the biologically active agent is incorporated into the microparticle. The biologically active agent can be, for example, factors which modulate cell growth.

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 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 - 60 . (Canceled)