Methods of recellularizing a tissue or organ for improved transplantability
Inventors
Taylor, Doris • Kren, Stefan M.
Assignees
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Publication Number
US-12084677-B2
Publication Date
2024-09-10
Expiration Date
Abstract
Described herein are methods of recellularizing an organ or tissue matrix.
Core Innovation
The invention relates to an ex vivo method of reendothelializing a decellularized mammalian tissue or organ matrix. A decellularized mammalian vascularized tissue or organ matrix is perfused with a physiological buffer under pressure so that the vascular system retains fluid and exits through a different route when fluid is introduced to one entry point. The method targets reendothelialization of the vascularized matrix while preserving the patent vasculature and fluid-retaining pathways.
Reendothelialization is performed by perfusing, antegrade and retrograde, the decellularized mammalian tissue or organ matrix with a physiological composition comprising a substantially pure population of endothelial cells or endothelial progenitor cells. The enhanced reendothelialization is stated to occur after perfusing a composition having the cells antegrade and retrograde, relative to reendothelialization after perfusing a composition having the same number of cells antegrade or retrograde. The vascular system is therefore reendothelialized through multi-directional perfusion with endothelial or endothelial progenitor cell populations.
The invention further supports reendothelialized tissue or organ matrices that are suitable for transplantation into a human recipient. A recellularized tissue or organ following transplantation is used to reduce thrombogenesis and immunogenicity, including by providing the pressure-perfused, fluid-retaining decellularized mammalian vascularized tissue or organ matrix, reendothelializing it with the antegrade and retrograde perfused endothelial or endothelial progenitor cell composition, and transplanting the reendothelialized construct.
Claims Coverage
The document includes two independent claims. Collectively, they cover pressure-perfused, fluid-retaining decellularized mammalian vascularized tissue or organ matrices, antegrade and retrograde perfusion with a substantially pure population of endothelial cells or endothelial progenitor cells, enhanced reendothelialization, and transplantation into a human recipient to reduce thrombogenesis and immunogenicity.
Pressure-perfused fluid-retaining decellularized vascularized matrix
Providing a decellularized mammalian vascularized tissue or organ matrix perfused with a physiological buffer under pressure, wherein the vascular system retains fluid so that it exits through a different route of the vascular system.
Antegrade and retrograde reendothelialization with substantially pure endothelial or EPC cells
Reendothelializing the decellularized vascularized mammalian tissue or organ matrix by perfusing, antegrade and retrograde, with a physiological composition comprising a substantially pure population of endothelial cells or endothelial progenitor cells.
Enhanced reendothelialization by combining antegrade and retrograde cellular perfusion
Reendothelialization after perfusing the composition having the cells antegrade and retrograde is enhanced relative to reendothelialization after perfusing a composition having the same number of cells antegrade or retrograde.
Reducing thrombogenesis and immunogenicity after transplantation into a human recipient
Reducing thrombogenesis and immunogenicity in a recellularized tissue or organ following transplantation into a human recipient by providing the pressure-perfused matrix, reendothelializing it with the antegrade and retrograde cell composition, and transplanting the reendothelialized tissue or organ matrix.
The key inventive coverage centers on pressure perfusion of a decellularized mammalian vascularized matrix that retains fluid, followed by enhanced reendothelialization using a substantially pure endothelial cell or endothelial progenitor cell composition delivered by both antegrade and retrograde perfusion, with a stated goal of reducing thrombogenesis and immunogenicity after transplantation into a human recipient.
Stated Advantages
Reduction of thrombogenesis and immunogenicity in a recellularized tissue or organ following transplantation into a human recipient.
Enhanced reendothelialization after perfusing a composition having the cells antegrade and retrograde compared with perfusing the same number of cells antegrade or retrograde.
Documented Applications
Reendothelialization of a decellularized mammalian vascularized tissue or organ matrix ex vivo to produce a recellularized tissue or organ for transplantation.
Use after transplantation into a human recipient to reduce thrombogenesis and immunogenicity.
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