Methods of recellularizing a tissue or organ for improved transplantability
Inventors
Taylor, Doris • Kren, Stefan M.
Assignees
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Publication Number
US-10233420-B2
Publication Date
2019-03-19
Expiration Date
Abstract
Described herein are methods of recellularizing an organ or tissue matrix.
Core Innovation
The invention relates to ex vivo reendothelializing a perfusion decellularized mammalian tissue or organ matrix having a vascular system in which fluid introduced to one entry point is retained so that it exits through a different route of the vascular system. The recellularization and re-endothelialization are performed by perfusing the decellularized vasculature with a physiological composition comprising a substantially pure population of endothelial cells or endothelial progenitor cells.
The method includes perfusing the decellularized vasculature antegrade and retrograde. The reendothelialization and thrombomodulin activity of the decellularized mammalian tissue or organ matrix 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.
The invention also relates to reducing thrombogenesis and immunogenicity in a recellularized tissue or organ following transplantation into a recipient. In this approach, a perfusion decellularized matrix is perfused with a physiological buffer under pressure, reendothelialized by antegrade and retrograde perfusion with a substantially pure population of endothelial cells or endothelial progenitor cells, and then transplanted into the recipient.
Claims Coverage
The independent claims are directed to three inventive features: ex vivo reendothelialization of a perfusion-decellularized mammalian vascularized tissue or organ matrix using a physiological composition with substantially pure endothelial cells or endothelial progenitor cells delivered both antegrade and retrograde, enhanced thrombomodulin activity from that delivery, and reduction of thrombogenesis and immunogenicity after transplantation.
Retained perfusion decellularized vascular system for reendothelialization
Providing a perfusion decellularized matrix of a mammalian vascularized tissue or organ wherein the matrix comprises a vascular system that retains fluid so that it exits through a different route of the vascular system.
Antegrade and retrograde physiological perfusion with substantially pure endothelial cells or EPCs
Reendothelializing by perfusing, antegrade and retrograde, the decellularized vasculature of the decellularized mammalian tissue or organ matrix with a physiological composition comprising a substantially pure population of endothelial cells or endothelial progenitor cells.
Enhanced thrombomodulin activity via antegrade and retrograde delivery
The reendothelialization and thrombomodulin activity 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.
Reduction of thrombogenesis and immunogenicity after transplantation
Reducing thrombogenesis and immunogenicity in a recellularized tissue or organ following transplantation into a recipient by perfusing a perfusion decellularized matrix with a physiological buffer under pressure, reendothelializing by perfusing antegrade and retrograde with an effective amount of a substantially pure population of endothelial cells or endothelial progenitor cells, and transplanting the reendothelialized tissue or organ matrix into the recipient.
Human endothelial cells or EPCs to enhance thrombomodulin activity in specific organs
Reendothelializing a decellularized kidney, liver, lung, or pancreas matrix by perfusing, antegrade and retrograde, the decellularized vasculature with a physiological composition comprising a substantially pure population of human endothelial cells or human endothelial progenitor cells in an amount effective to enhance thrombomodulin activity relative to reendothelialization after perfusing a corresponding decellularized matrix with the same number of cells antegrade or retrograde.
Across the independent claims, the inventive coverage centers on ex vivo perfusion-decellularized matrices with retained vascular fluid routes, reendothelialization by antegrade and retrograde perfusion using substantially pure endothelial cells or endothelial progenitor cells, and an enhanced thrombomodulin activity outcome. A further independent claim applies the recellularized product in a transplantation workflow to reduce thrombogenesis and immunogenicity.
Stated Advantages
Enhanced reendothelialization and thrombomodulin activity after antegrade and retrograde perfusion relative to antegrade-only or retrograde-only perfusion with the same number of cells.
Reduction of thrombogenesis and immunogenicity in a recellularized tissue or organ following transplantation into a recipient.
Documented Applications
Reducing thrombogenesis and immunogenicity in a recellularized tissue or organ following transplantation into a recipient.
Reendothelializing decellularized kidney, liver, lung, or pancreas matrices of a mammal ex vivo.
Reendothelializing a decellularized mammalian vascularized tissue or organ matrix ex vivo.
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