Bone augmentation utilizing muscle-derived progenitor compositions in biocompatible matrix, and treatments thereof

Abstract

The present invention provides muscle-derived progenitor cells that show long-term survival following transplantation into body tissues and which can augment non-soft tissue following introduction (e.g. via injection, transplantation, or implantation) into a site of non-soft tissue (e.g. bone) when combined with a biocompatible matrix, preferably SIS. The invention further provides methods of using compositions comprising muscle-derived progenitor cells with a biocompatible matrix for the augmentation and bulking of mammalian, including human, bone tissues in the treatment of various functional conditions, including osteoporosis, Paget's Disease, osteogenesis imperfecta, bone fracture, osteomalacia, decrease in bone trabecular strength, decrease in bone cortical strength and decrease in bone density with old age.

What is claimed is: 
     
         1 .- 34 . (canceled) 
     
     
         35 . A method of treating a bone disease, defect or pathology in a human subject in need thereof, wherein the method comprises administering to the human subject small intestine submucosa (SIS) seeded with a cell population enriched for muscle derived progenitor cells (MDCs), wherein the cell population enriched for MDCs is isolated from skeletal muscle by a method comprising:
 a. suspending skeletal muscle cells obtained from the human in a first cell culture container for between 30 and 120 minutes to produce a population of adherent cells and a population of non-adherent cells;   b. decanting media and the population of non-adherent cells from the first cell culture container to a second cell culture container;   c. allowing the population of decanted, non-adherent cells in the media to attach to the walls of the second cell culture container; and   d. isolating the population of cells from the walls of the second cell culture container, wherein the isolated population of cells is the cell population enriched for MDCs.   
     
     
         36 . The method of  claim 35 , wherein the isolation method further comprises culturing the cell population enriched for MDCs to expand their number before being used to seed the SIS. 
     
     
         37 . The method of  claim 36 , wherein the expanded cell population enriched for MDCs is frozen to a temperature below −30° C. after being cultured to expand their number and thawed prior to being used to seed SIS. 
     
     
         38 . The method of  claim 35 , wherein the isolation method further comprises cooling the skeletal muscle cells obtained from the human to a temperature below 10° C. and storing for 1-7 days before being suspended in a first cell culture container for between 30 and 120 minutes. 
     
     
         39 . The method of  claim 35 , wherein treating a bone disease, defect or pathology comprises augmenting bone. 
     
     
         40 . The method of  claim 35 , wherein treating a bone disease, defect or pathology comprises increasing bone volume or bone density. 
     
     
         41 . The method of  claim 35 , wherein treating a bone disease, defect or pathology comprises treatment of osteoporosis, Paget's Disease, osteogenesis imperfecta, bone fracture, osteomalacia, decrease in bone trabecular strength, decrease in bone cortical strength, or decrease in bone density with old age. 
     
     
         42 . The method of  claim 35 , wherein the bone defect is a bone fracture caused by trauma. 
     
     
         43 . The method of  claim 35 , wherein the SIS seeded with a cell population enriched for MDCs is administered by applying it to the surface of the bone. 
     
     
         44 . The method of  claim 35 , wherein the SIS seeded with a cell population enriched for MDCs is positioned in the interior of the bone.