Acellular tissue matrices made from alpa-1,3-galactose-deficient tissue

Abstract

The invention provides acellular tissue matrices made from collagen-containing tissues of animals genetically modified so as to be deficient in the galactose 1,3-galactose epitope and methods of making and using such acellular tissue matrices.

1 . An acellular tissue matrix comprising: 
 a decellularized collagen-containing tissue, or a decellularized collagen-containing organ, of an animal genetically modified such that tissues in the animal lack, or substantially lack, galactose α-1,3-galactose epitopes,    wherein the acellular tissue matrix lacks, or substantially lacks, epithelial basement membrane.    
     
     
         2 . The product of  claim 1 , wherein the animal is a pig.  
     
     
         3 . The product of  claim 1 , wherein the tissue or organ is dermis.  
     
     
         4 . The product of  claim 1 , wherein the tissue or organ is selected from the group consisting of fascia, pericardium, dura, umbilical cord, placenta, cardiac valve, ligament, tendon, artery, vein, neural connective tissue, intestine, bladder, and ureter.  
     
     
         5 . The product of  claim 1 , wherein the acellular tissue matrix is in non-particulate form.  
     
     
         6 . The product of  claim 1 , wherein the acellular tissue matrix is in particulate form.  
     
     
         7 . The product of  claim 1 , wherein the genetic modification comprises a disruption of both alleles of an α-1,3 galactosyl transferase (αGT) gene.  
     
     
         8 . A method of making an acellular tissue matrix, the method comprising: 
 (a) providing a collagen-containing tissue or a collagen-containing organ from an animal genetically modified so that tissues in the animal lack, or substantially lack, galactose α-1,3-galactose epitopes; and    (b) processing the tissue or organ to so as to render the tissue or organ acellular and lacking, or substantially lacking, in epithelial basement membrane, the processing resulting in the production of an acellular tissue matrix.    
     
     
         9 . The method of  claim 8 , wherein the animal is a pig.  
     
     
         10 . The method of  claim 8 , wherein the tissue or organ comprises dermis.  
     
     
         11 . The method of  claim 8 , wherein the tissue or organ is selected from the group consisting of fascia, pericardium, dura, umbilical cord, placenta, cardiac valve, ligament, tendon, artery, vein, neural connective tissue, intestine, bladder, and ureter.  
     
     
         12 . The method of  claim 8 , wherein the genetic modification comprises a disruption of both alleles of an α-1,3 galactosyl transferase (αGT) gene.  
     
     
         13 . The method of  claim 8 , further comprising freezing the acellular tissue matrix.  
     
     
         14 . The method of  claim 8 , further comprising freeze-drying the acellular tissue matrix.  
     
     
         15 . The method of  claim 8 , further comprising: 
 (a) pulverizing the acellular tissue matrix; or    (b) rendering the acellular tissue matrix particulate in form.    
     
     
         16 . The method of  claim 10 , wherein the process comprises removing and discarding epidermis.  
     
     
         17 . A method of treatment, the method comprising: 
 (a) identifying a mammalian subject as having an or organ, or tissue, in need of repair or amelioration; and    (b) placing a composition comprising the product of  claim 1  in or on the organ or tissue.    
     
     
         18 . The method of  claim 1 , wherein the subject is a human.  
     
     
         19 . The method of  claim 17 , wherein the animal is a pig.  
     
     
         20 . The method of  claim 17 , wherein the tissue or organ is dermis.  
     
     
         21 . The method of  claim 17 , wherein the tissue or organ is selected from the group consisting of fascia, umbilical cord, placenta, cardiac valve, ligament, tendon, artery, vein, neural connective tissue, intestine, bladder, and ureter.  
     
     
         22 . The method of  claim 17 , wherein the acellular tissue matrix is in non-particulate form.  
     
     
         23 . The method of  claim 17 , wherein the acellular tissue matrix is in particulate form.  
     
     
         24 . The method of  claim 17 , wherein the genetic modification comprises disruption of both alleles of an α-1,3 galactosyl transferase (αGT) gene.  
     
     
         25 . The method of  claim 17 , further comprising administration to the subject of one or more agents selected from the group consisting of a cell growth factor, an angiogenic factor, a differentiation factor, a cytokine, a hormone, and a chemokine.  
     
     
         26 . The method of  claim 25 , wherein the one or more agents are in the composition placed in the subject.  
     
     
         27 . The method of  claim 25 , wherein the administration comprises injecting or infusing the one or more agents into the mammalian subject separately from the composition.  
     
     
         28 . The method of  claim 17 , wherein the organ or tissue of the subject is selected from the group consisting of skin, bone, cartilage, meniscus, dermis, myocardium, periosteum, artery, vein, stomach, small intestine, large intestine, diaphragm, tendon, ligament, neural tissue, striated muscle, smooth muscle, bladder, urethra, ureter, and gingiva.  
     
     
         29 . The method of  claim 17 , wherein the organ or tissue of the subject is abdominal wall fascia.  
     
     
         30 . The method of  claim 17 , wherein the composition further comprises demineralized bone powder.  
     
     
         31 . The method of  claim 28 , wherein the gingiva is, or is proximal to, receding gingiva.  
     
     
         32 . The method of  claim 28 , wherein the gingiva comprises a dental extraction socket.