Decellularization and recellularization of solid organs

Abstract

The invention provides for methods and materials to decellularize a solid organ and to recellularize such a decellularized organ to thereby generate a solid organ.

1 . A perfusion decellularized pig, bovine, sheep, canine, or human organ or portion thereof, comprising
 a decellularized extracellular matrix that comprises a substantially intact exterior surface and a vascular tree comprising a substantially intact vascular bed, wherein said vascular tree retains a majority of fluid introduced to said vascular tree, and wherein said perfusion decellularized pig, bovine, sheep, canine, or human organ or portion thereof further comprises a cannula attached to a cavity, a vessel, or a duct of said organ or portion thereof.   
     
     
         2 . The perfusion decellularized organ of  claim 1 , wherein said perfusion decellularized organ is cadaveric. 
     
     
         3 . The perfusion decellularized organ of  claim 1 , wherein said perfusion decellularized organ is a heart, a kidney, a liver, a spleen, a heart, a pancreas, a lung, or a portion of any of these. 
     
     
         4 . (canceled) 
     
     
         5 . (canceled) 
     
     
         6 . The perfusion decellularized organ of  claim 3 , wherein said perfusion decellularized organ is said heart or said portion thereof and is: an aortic valve, a mitral valve, a pulmonary valve, a tricuspid valve, a right atrium, a left atrium, a right ventricle, a left ventricle, a cardiac patch, septum, a coronary vessel, a pulmonary artery, or a pulmonary vein. 
     
     
         7 . (canceled) 
     
     
         8 . The perfusion decellularized organ of  claim 3 , wherein said perfusion decellularized organ is said kidney or said portion thereof. 
     
     
         9 . The perfusion decellularized organ of  claim 8 , wherein said kidney or said portion thereof comprises a substantially intact glomerular structure. 
     
     
         10 . A system, comprising said perfusion decellularized organ or portion thereof of  claim 1 , and at least one of a: bioreactor, perfusion apparatus, containment system, sensor, thermometer, electrode, overflow valve, balloon, pacemaker, compliance chamber, a computer-readable storage medium, or programmable processor. 
     
     
         11 . The system of  claim 10 , wherein said system comprises said perfusion apparatus, wherein said perfusion apparatus comprises a holding container and a mechanism for moving a liquid through said perfusion decellularized organ or portion thereof. 
     
     
         12 . The system of  claim 10 , wherein said system comprises said sensor, wherein said sensor monitors at least one of: pressure of a liquid moving through said cannulated organ or portion thereof, temperature of said system, temperature of said perfusion decellularized organ or portion thereof, biological activity of said perfusion decellularized organ or portion thereof. 
     
     
         13 . The system of  claim 10 , wherein said system comprises said computer-readable storage medium, said bioreactor, and said programmable processor, wherein said computer-readable storage medium in combination with said programmable processor performs at least one of: receiving and processing information from said sensor, transmitting information and instructions to said bioreactor, monitoring or maintaining said perfusion decellularized organ or portion thereof, calculating an exposure time, calculating a perfusion pressure, recording a pressure, recording a flow rate, adjusting a perfusion pressure, adjusting a perfusion direction, or adjusting a perfusion solution. 
     
     
         14 . The system of  claim 13 , wherein said computer-readable storage medium comprises instructions stored thereon for causing said programmable processor to perform a decellularization step or a recellularization step. 
     
     
         15 . The system of  claim 10 , further comprising a second cannula. 
     
     
         16 . The system of  claim 11 , wherein said liquid comprises a cellular disruption medium, a wash solution, an antibiotic, an anti-fungal, an anti-microbial, or a solution comprising an enzyme. 
     
     
         17 . The system of  claim 10 , wherein said system comprises said perfusion decellularized organ. 
     
     
         18 . The system of  claim 10 , wherein said system is used for recellularization or decellularization. 
     
     
         19 . The system of  claim 10 , wherein said perfusion apparatus further comprises a pump, and wherein said pump is a piston pump, infusion pump, roller pump, or a peristaltic pump. 
     
     
         20 . The system of  claim 11 , wherein said perfusion apparatus further comprises a pump and said balloon, and wherein said pump is connected to said balloon or said cannula. 
     
     
         21 . The system of  claim 10 , wherein said system further comprises an ECG recorder. 
     
     
         22 . The system of  claim 10 , wherein said perfusion decellularized organ or portion thereof is a heart or portion thereof, wherein said system comprises said sensor, and wherein said sensor is placed in an arterial or venous line of said heart or portion thereof. 
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . (canceled) 
     
     
         32 . (canceled) 
     
     
         33 . (canceled) 
     
     
         34 . (canceled) 
     
     
         35 . (canceled) 
     
     
         36 . A perfusion decellularized vascular mammalian tissue, comprising
 a decellularized extracellular matrix of said perfusion decellularized vascular mammalian tissue, wherein said decellularized extracellular matrix comprises a substantially intact exterior surface and a vascular tree comprising a substantially intact vascular bed, wherein said vascular tree retains a majority of fluid introduced to said vascular tree, and wherein said perfusion decellularized vascular mammalian tissue further comprises a cannula attached to a cavity, a vessel, or a duct.   
     
     
         37 . The perfusion decellularized vascular mammalian tissue of  claim 36 , wherein said tissue is cadaveric. 
     
     
         38 . The perfusion decellularized vascular mammalian tissue of  claim 36 , wherein said tissue is spinal cord, trachea, or a joint, or a portion of any of these. 
     
     
         39 . A containment system comprising a decellularized avascular mammalian tissue, comprising
 a decellularized extracellular matrix of said avascular mammalian tissue, wherein said extracellular matrix comprises a substantially intact exterior surface, and wherein said decellularized extracellular matrix substantially retains the morphology of said decellularized extracellular matrix prior to decellularization.   
     
     
         40 . The containment system of  claim 39 , wherein said tissue is at least a portion of a cartilage or cornea. 
     
     
         41 . The containment system of  claim 39 , wherein said tissue is cadaveric. 
     
     
         42 . The perfusion decellularized organ of  claim 3 , wherein said organ is said liver or said portion thereof. 
     
     
         43 . The perfusion decellularized organ of  claim 3 , wherein said organ is said spleen or said portion thereof. 
     
     
         44 . The perfusion decellularized organ of  claim 3 , wherein said organ is said pancreas or said portion thereof. 
     
     
         45 . The perfusion decellularized organ of  claim 3 , wherein said organ is said lung or said portion thereof.