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US 10,441,609 B2Granted
Decellularization and recellularization of solid organs
AssigneeMiromatrix Medical Inc.
InventorsHarald Ott, Doris Taylor
Life of this patent
Estimating the term…
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.
Claims52
A method, comprising
- providing a decellularized extracellular matrix of a decellularized mammalian organ that retains the morphology of said extracellular matrix prior to decellularization, wherein said decellularized extracellular matrix of said decellularized organ comprises an intact exterior surface, wherein said decellularized extracellular matrix of said decellularized organ comprises the extracellular matrix components of a vascular tree comprising an intact vascular bed, and wherein said decellularized extracellular matrix retains a majority of fluid introduced to the decellularized extracellular matrix vascular tree;
- and
- introducing a population of cells to the decellularized matrix, or a vessel, a duct, or a cavity of said decellularized extracellular matrix;
- and
- perfusing a first solution into the vessel, the duct, or the cavity of the decellularized extracellular matrix, or injecting the first solution into the decellularized extracellular matrix, so that at least some of said cells distribute within and on said at least a portion of said decellularized extracellular matrix, thereby providing a recellularized extracellular matrix of the decellularized mammalian organ.
2 more elements
An ex vivo method of recellularization of a decellularized mammalian organ comprising
- providing a decellularized extracellular matrix of a decellularized mammalian organ, wherein said decellularized extracellular matrix of said decellularized organ comprises an intact exterior surface, wherein said decellularized organ comprises the extracellular matrix components of a vascular tree comprising an intact vascular bed, and wherein said decellularized extracellular matrix retains a majority of fluid introduced to the decellularized extracellular matrix vascular tree;
- perfusing or injecting said decellularized organ prior to recellularization with a solution comprising one or more compounds thereby generating a perfused decellularized organ;
- and
- introducing a population of cells to said perfused decellularized organ, wherein the one or more compounds stimulate at least some of the cells as compared to a comparable population of cells that undergo said introducing but are absent said perfusing.
1 more element
A method for recellularizing an extracellular matrix of a decellularized mammalian organ, comprising
- providing a decellularized extracellular matrix of a decellularized mammalian organ that retains the morphology of said extracellular matrix prior to decellularization, wherein said decellularized extracellular matrix of said decellularized organ comprises an intact exterior surface, wherein said decellularized extracellular matrix of said decellularized organ comprises the extracellular matrix components of a vascular tree comprising an intact vascular bed, and wherein said decellularized extracellular matrix retains a majority of fluid introduced to the decellularized extracellular matrix vascular tree;
- and
- introducing a population of stem cells to the decellularized extracellular matrix, or a vessel, a duct, or a cavity, of said decellularized extracellular matrix;
- and
- perfusing a solution into the vessel, the duct, or the cavity of the decellularized extracellular matrix, or injecting the solution into the decellularized extracellular matrix, so that at least some of said stem cells distribute within and on at least a portion of said decellularized extracellular matrix, thereby providing a recellularized extracellular matrix of the decellularized mammalian organ.
2 more elements
A method for recellularizing an extracellular matrix of a decellularized mammalian liver, comprising
- providing a decellularized extracellular matrix of a decellularized mammalian liver that retains the morphology of said extracellular matrix prior to decellularization, wherein said decellularized extracellular matrix of said decellularized liver comprises an intact exterior surface, wherein said decellularized extracellular matrix of said decellularized liver comprises the extracellular matrix components of a vascular tree comprising an intact vascular bed, and wherein said decellularized extracellular matrix retains a majority of fluid introduced to the decellularized extracellular matrix vascular tree;
- and
- perfusing a population of endothelial cells or liver-specific cells and a first solution into a vessel, a duct or a cavity of said decellularized extracellular matrix so that said endothelial cells distribute and engraft in the vascular tree or said liver-specific cells distribute and engraft in the cavity, and optionally multiply, wherein the endothelial cells re-endothelialize the vascular tree and the liver-specific cells have an organ-specific activity of corresponding cells present in the liver prior to decellularization.
A method for recellularizing an extracellular matrix of a decellularized human or pig liver, comprising:
- providing a decellularized extracellular matrix of a decellularized human or pig liver that retains the morphology of said extracellular matrix prior to decellularization, wherein said decellularized extracellular matrix of said decellularized human or pig liver comprises an intact exterior surface, wherein said decellularized extracellular matrix of said decellularized human or pig liver comprises the extracellular matrix components of a vascular tree comprising an intact vascular bed, and wherein said decellularized extracellular matrix retains a majority of fluid introduced to the decellularized extracellular matrix vascular tree;
- selecting an amount of human or pig endothelial cells and hepatocytes for recellularization;
- and
- introducing the human and pig endothelial cells or hepatocytes to a vessel or a duct of said decellularized extracellular matrix and perfusing a solution into the vessel or duct of the decellularized extracellular matrix so that said endothelial cells and hepatocytes distribute and engraft, and optionally multiply, within and on said decellularized extracellular matrix, thereby providing a recellularized human or pig liver decellularized extracellular matrix having engrafted human or pig hepatocytes with an activity of cells of the human or pig liver prior to decellularization and having engrafted human or pig endothelial cells that re-endothelialize the vascular tree.
1 more element
A method for recellularizing an extracellular matrix of a decellularized human or pig liver, comprising
- providing in a bioreactor a decellularized extracellular matrix of a decellularized human or pig liver that retains the morphology of said extracellular matrix prior to decellularization, wherein said decellularized extracellular matrix of said decellularized human or pig liver comprises an intact exterior surface, wherein said decellularized extracellular matrix of said decellularized human or pig liver comprises the extracellular matrix components of a vascular tree comprising an intact vascular bed, and wherein said decellularized extracellular matrix retains a majority of fluid introduced to the decellularized extracellular matrix vascular tree;
- perfusing a population of human or pig endothelial cells or liver-specific cells in a first solution into a vessel or a duct of said decellularized extracellular matrix so that said endothelial cells distribute and engraft and optionally multiply in the vascular tree or said liver-specific cells distribute and engraft and optionally multiply, wherein the engrafted endothelial cells re-endothelialize the vascular tree and the engrafted liver-specific cells have an activity of corresponding cells present in the liver prior to decellularization;
- and
- perfusing a second solution into the re-endothelialized vessel to maintain the viability of the cells in the recellularized liver.
1 more element
A method for recellularizing an extracellular matrix of a decellularized human or pig liver, comprising
- providing a decellularized extracellular matrix of a decellularized human or pig liver that retains the morphology of said extracellular matrix prior to decellularization, wherein said decellularized extracellular matrix of said decellularized human or pig liver comprises an intact exterior surface, wherein said decellularized extracellular matrix of said decellularized human or pig liver comprises the extracellular matrix components of a vascular tree comprising an intact vascular bed, and wherein said decellularized extracellular matrix retains a majority of fluid introduced to the decellularized extracellular matrix vascular tree;
- selecting an amount of human or pig endothelial cells or liver-specific cells for recellularization;
- perfusing a first solution through the extracellular matrix components of the vascular tree;
- and
- perfusing the human or pig endothelial cells or liver-specific cells in a second solution into a vessel or a duct of said decellularized extracellular matrix so that said endothelial cells distribute and engraft and optionally multiply in the vascular tree or said liver-specific cells distribute and engraft in the cavity and optionally multiply, wherein the engrafted endothelial cells re-endothelialize the vascular tree or the engrafted liver-specific cells have an activity of corresponding cells present in the liver prior to decellularization.
2 more elements
An at least partially recellularized organ comprising a perfusion decellularized extracellular matrix and at least about 10,000,000 regenerative cells engrafted thereon;
- wherein prior to the recellularization, the perfusion decellularized organ included an intact exterior surface, an intact, non-vasculature decellularized extracellular matrix and an intact, vasculature decellularized extracellular matrix, wherein said vasculature decellularized extracellular matrix retains a majority of fluid introduced to said vasculature decellularized extracellular matrix, wherein said vascular decellularized extracellular matrix comprises human cells, and wherein said decellularized extracellular matrix is from a kidney, lung, liver, pancreas, or spleen.
Dependencies are inferred from the claim text.