Treatment of Diseases and Disorders Using Self-Renewing Colony Forming Cells Cultured and Expanded In Vitro

Abstract

The present invention relates to methods and uses of cells for the prevention and treatment of a wide variety of diseases and disorders and the repair and regeneration of tissues and organs using low passage and extensively passaged in vitro cultured, self-renewing, colony forming somatic cells (CF-SC). For example, adult bone marrow-derived somatic cells (ABM-SC), or compositions produced by such cells, are useful alone or in combination with other components for treating, for example, cardiovascular, neurological, integumentary, dermatological, periodontal, and immune mediated diseases, disorders, pathologies, and injuries.

1 - 94 . (canceled) 
     
     
         95 . A biocompatible matrix comprising conditioned cell culture media derived from an isolated population of bone marrow-derived self-renewing colony-forming somatic cells (CF-SC), wherein the CF-SC do not have multipotent differentiation capacity, wherein the CF-SC have a normal karyotype, wherein the CF-SC are non-immortalized, and wherein the CF-SC express CD13, CD44, CD49c, CD90, HLA Class-1 and β (beta) 2-Microglobulin, and wherein the CF-SC do not express CD10, CD34, CD45, CD62L, or CD106. 
     
     
         96 . The biocompatible matrix of  claim 95 , wherein the CF-SC further express one or more molecules selected from the group consisting of CD29, CD59, CD147, CD166 and telomerase, and wherein the CF-SC further do not express one or more molecules selected from the group consisting of CD11c, CD14, CD33, CD62P, CD80, STRO-1, CD178, p53 and p21. 
     
     
         97 . The biocompatible matrix of  claim 95 , wherein the CF-SC cells were obtained from bone marrow by a method comprising:
 (a) incubating bone marrow cells under a low oxygen condition such that the bone marrow cells when allowed to adhere to a tissue culture-treated surface produce adherent colony forming units; and,   (b) passaging cells in the adherent colony forming units at low cell seeding densities.   
     
     
         98 . The biocompatible matrix of  claim 97 , wherein the low oxygen condition comprises between about 1 to 10% oxygen. 
     
     
         99 . The biocompatible matrix of  claim 97 , wherein the low cell seeding density is less than about 2500 cells/cm 2 . 
     
     
         100 . The biocompatible matrix of  claim 95 , wherein the matrix is biodegradable. 
     
     
         101 . The biocompatible matrix of  claim 100 , wherein the matrix comprises collagen, fibrin, polyglycolic acid (PGA), or combinations thereof. 
     
     
         102 . The biocompatible matrix of  claim 101 , wherein the matrix comprises PGA. 
     
     
         103 . The biocompatible matrix of  claim 95 , wherein the conditioned cell culture media is serum free. 
     
     
         104 . The biocompatible matrix of  claim 103 , further comprising at least one pharmaceutical compound. 
     
     
         105 . The biocompatible matrix of  claim 104 , wherein the at least one pharmaceutical compound is selected from the group consisting of anti-inflammatories, antibiotics, vitamins, minerals, extracellular matrix proteins, blood plasma coagulation proteins, antibodies, growth factors, chemokines, cytokines, lipids and nucleic acids. 
     
     
         106 . A method of preparing a medical device, comprising:
 contacting conditioned cell culture media derived from bone marrow-derived self-renewing colony-forming somatic cells (CF-SC) with a biocompatible matrix to form a medical device,
 wherein the CF-SC do not have multipotent differentiation capacity, wherein the CF-SC have a normal karyotype, wherein the CF-SC are non-immortalized, and wherein the CF-SC express CD13, CD44, CD49c, CD90, HLA Class-1 and β (beta) 2-Microglobulin, and wherein the CF-SC do not express CD10, CD34, CD45, CD62L, or CD106. 
   
     
     
         107 . The method of  claim 106 , wherein the conditioned cell culture media is derived from CF-SC cells cultured under a low oxygen condition comprising between about 1 to 10% oxygen. 
     
     
         108 . The method of  claim 106 , wherein the matrix comprises collagen, fibrin, polyglycolic acid (PGA), or combinations thereof. 
     
     
         109 . The method of  claim 108 , wherein the matrix comprises PGA. 
     
     
         110 . A method of repairing, treating, or promoting regeneration of damaged tissue, comprising contacting a subject in need thereof with a therapeutically effective amount of the biocompatible matrix of  claim 95 . 
     
     
         111 . The method of  claim 110 , wherein the matrix further comprises at least one pharmaceutical compound. 
     
     
         112 . The method of  claim 110 , wherein the tissue damage was caused by an immune related disorder, inflammation, ischemia, traumatic injury, or infection. 
     
     
         113 . The method of  claim 110 , wherein the damaged tissue is skin, bone, connective tissue, or cartilage. 
     
     
         114 . The method of  claim 113 , wherein the connective tissue comprises tendon or ligament. 
     
     
         115 . The method of  claim 110 , wherein the tissue damage is a diabetic ulcer.