Decellularization and recellularization of organs and tissues
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 decellularized pig, bovine, sheep, canine or human organ, comprising
a decellularized extracellular matrix of said organ, wherein said extracellular matrix comprises an intact exterior surface and a vascular tree, wherein said decellularized extracellular matrix of said organ retains a majority of fluid introduced to the decellularized extracellular matrix vascular tree.
2. The decellularized organ of claim 1 , whereinsaid organ is cadaveric.
3. The decellularized organ of claim 1 , wherein said organ is a heart.
4. The decellularized organ of claim 3 , wherein said heart is a pig heart, a bovine heart, a sheep heart, or a canine heart.
5. The decellularized organ of claim 3 , wherein said heart is a human heart.
6. The deceliularized organ of claim 1 , wherein said organ is a kidney.
7. The decellularized organ of claim 6 , wherein said kidney comprises an intact glomerular structure.
8. A method of decellularizing a pig, bovine, sheep, canine, or human organ, comprising: providing said organ; cannulating said organ at one or more cavities, vessels, and/or ducts, thereby producing a cannulated organ; and perfusing said cannulated organ with a first cellular disruption medium so as to yield a decellularized pig, bovine, sheep, canine, or human organ comprising an extracellular matrix having an exterior surface and a vascular tree, and wherein said decellularized extracellular matrix of said organ retains a majority of fluid introduced into the decellularized extracellular matrix vascular tree.
9. The method of claim 8 , wherein essentially the entire vascular tree is contacted with the first cellular disruption medium.
10. The method of claim 8 , wherein said organ is a heart, a kidney, a liver, spleen, pancreas, or a lung.
11. The method of claim 8 , wherein said perfusion is multi-directional from each cannulated cavity, vessel, and/or duct.
12. The method of claim 8 , wherein said cellular disruption medium comprises at least one detergent.
13. The method of claim 12 , wherein said detergent is selected from the group consisting of SDS, PEG, or Triton X.
14. The method of claim 8 , further comprising perfusing said cannulated organ with a second cellular disruption medium.
15. The method of claim 14 , wherein said first cellular disruption medium is an anionic detergent and wherein said second cellular disruption medium is a non-ionic detergent,
16. The method of claim 15 , wherein the anionic detergent is SDS and wherein said non-ionic detergent is Triton X.
17. The method of claim 8 , wherein said perfusing is for about 2 to 12 hours per gram of organ tissue.
18. The decellularized organ of claim 1 ., wherein said organ is a lung, liver, spleen or pancreas.
19. A perfusion decellularized extracellular matrix of a mammalian organ prepared by perfusing a mammalian organ from a pig, bovine, sheep, canine or human through one or more cavities, vessels, and/or ducts with a first cellular disruption medium, so as to yield a decellularized pig, bovine, sheep, canine or human organ comprising extracellular matrix having an exterior surface and a vascular tree, wherein said decellularized extracellular matrix of said organ retains a majority of fluid introduced to the decellularized extracellular matrix vascular tree.
20. The perfusion decellularized extracellular matrix of claim 19 wherein said mammalian organ is a heart.
21. The perfusion decellularized extraceliular matrix of claim 19 wherein said mammalian organ is a kidney.
22. The perfusion decellularized extacellular matrix of claim 21 which comprises an intact glomerular structure.
23. The perfusion decellularized extracellular matrix of claim 19 wherein said mammalian organ is a liver.
24. The perfusion decellularized extracellular matrix of claim 19 wherein said mammalian organ is a pancreas.
25. The perfusion decellularized extracellular matrix of claim 19 wherein said mammalian organ is a spleen or lung.
26. The decellularized organ of claim 1 , wherein said organ is a bone.
27. The perfusion decellularized extracellular matrix of claim 19 , wherein said mammalian organ is a bone.
28. The method of claim 8 , wherein said organ is a bone.