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.

1 - 34 . (canceled) 
     
     
         35 . A method of accelerating formation of mineralized matrix on small intestine submucosa (SIS) sheets and/or scaffolds comprising seeding SIS disks with human muscle-derived progenitor cells (hMDCs) in an osteogenic medium to form SIS sheets, wherein the mineralization is achieved within 7 days; wherein the mineralization is accelerated compared to SIS scaffolds not seeded with hMDCs (empty SIS) cultured in the osteogenic medium. 
     
     
         36 . The method of  claim 35 , wherein the hMDCs seeded SIS disks are incubated for 28 days in the osteogenic medium. 
     
     
         37 . The method of  claim 35 , wherein volume of the mineralized matrix is progressively increased as observed at 7 days, at 10 days, at 14 days, at 21 days, and at 28 days. 
     
     
         38 . The method of  claim 37 , wherein density of the mineralized matrix in SIS scaffolds with hMDCs cultivated in the osteogenic medium is about 222 mm HA/ccm at 7 days. 
     
     
         39 . The method of  claim 37 , wherein density of the mineralized matrix in SIS scaffolds with hMDCs cultivated in the osteogenic medium is about 200 mm HA/ccm at 28 days. 
     
     
         40 . The method of  claim 35 , wherein the empty SIS scaffolds cultured in the osteogenic medium has a mineralized matrix density of about 170 mm HA/ccm at 28 days. 
     
     
         41 . The method of  claim 35 , wherein the hMDCs are in the form of cell pellets. 
     
     
         42 . A method of repairing a calvarial defect of a mammalian subject in need thereof, comprising preconditioning a single-layer of small intestine submucosa (SIS) by seeding with muscle-derived progenitor cells (MDCs) before transplanting into the calvarial defect of the mammalian subject. 
     
     
         43 . The method of  claim 42 , wherein the SIS is seeded with the MDCs twelve hours before transplanting into the calvarial defect of the mammalian subject. 
     
     
         44 . The method of  claim 42 , wherein the calvarial defect is repaired by formation of new bone. 
     
     
         45 . The method of  claim 44 , wherein the new bone is formed within 4 weeks. 
     
     
         46 . The method of  claim 44 , wherein the new bone is formed within 10 weeks. 
     
     
         47 . The method of  claim 42 , wherein the MDCs are isolated by a method comprising:
 (i) isolating skeletal muscle from a mammal,   (ii) suspending the mammalian skeletal muscle in a medium in a first cell culture container for between 30 and 120 minutes thereby producing a cell population of adherent cells and a population of non-adherent cells;   (iii) decanting the medium and the population of the non-adherent cells from the first cell culture container to a second cell culture container;   (iv) allowing the population of the decanted non-adherent cells in the medium from the first cell culture container to attach to the walls of the second cell culture container for 1-3 days; and   (v) isolating the population of cells from the walls of the second cell culture container, wherein the isolated cells are MDCs.