Methods of recellularizing a tissue or organ for improved transplantability
Inventors
Taylor, Doris • Kren, Stefan M.
Assignees
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Publication Number
US-11414644-B2
Publication Date
2022-08-16
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 perfusion decellularized mammalian tissue or organ matrix by providing a perfusion decellularized mammalian tissue or organ matrix perfused with a physiological buffer under pressure, followed by reendothelialization. Reendothelialization is performed by perfusing the decellularized mammalian tissue or organ matrix with a physiological composition comprising a substantially pure population of mammalian endothelial cells or mammalian endothelial progenitor cells.
A central feature is that the endothelial cells or endothelial progenitor cells are perfused antegrade and retrograde, and that 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. The disclosed approach is also presented as improving cellular distribution and preserving endothelial phenotype/function in perfused recellularized tissue or organ matrices.
In further aspects, the invention addresses post-transplant outcomes by providing a decellularized mammalian tissue or organ matrix perfused with a physiological buffer under pressure, reendothelializing with a physiological composition comprising an amount of a substantially pure population of mammalian endothelial cells or mammalian endothelial progenitor cells using antegrade and retrograde perfusion, and transplanting the reendothelialized tissue or organ into a mammalian recipient. The resulting reendothelialized tissue or organ has reduced thrombogenesis and immunogenicity relative to a corresponding tissue or organ re-endothelialized antegrade or retrograde with the same amount of cells.
Claims Coverage
The independent claims are clm-00001 and clm-00009. Both claims emphasize reendothelialization using a substantially pure population of mammalian endothelial cells or mammalian endothelial progenitor cells with physiological buffer perfusion under pressure, and the use of both antegrade and retrograde perfusion to enhance outcomes.
Enhanced antegrade and retrograde reendothelialization of perfusion decellularized matrices
An ex vivo method comprising providing a perfusion decellularized mammalian tissue or organ matrix perfused with a physiological buffer under pressure and reendothelializing the perfusion decellularized mammalian tissue or organ matrix by perfusing, antegrade and retrograde, with a physiological composition comprising a substantially pure population of mammalian endothelial cells or mammalian endothelial progenitor cells, wherein reendothelialization is enhanced relative to reendothelialization after perfusing the same number of cells antegrade or retrograde.
Reducing thrombogenesis and immunogenicity by antegrade and retrograde reendothelialization prior to transplantation
A method reducing thrombogenesis and immunogenicity in a recellularized mammalian tissue or organ following transplantation into a mammalian recipient by providing a decellularized mammalian tissue or organ matrix perfused with a physiological buffer under pressure, reendothelializing by perfusing, antegrade and retrograde, with a physiological composition comprising an amount of a substantially pure population of mammalian endothelial cells or mammalian endothelial progenitor cells, and transplanting the reendothelialized tissue or organ into the mammalian recipient, wherein the reendothelialized tissue or organ has reduced thrombogenesis and immunogenicity relative to a corresponding tissue or organ matrix reendothelialized antegrade or retrograde with the same amount of cells.
Overall, claim coverage centers on reendothelializing perfusion decellularized mammalian tissue or organ matrices using substantially pure populations of endothelial cells or endothelial progenitor cells, delivered antegrade and retrograde to enhance reendothelialization and, after transplantation, reduce thrombogenesis and immunogenicity versus single-direction delivery with the same amount of cells.
Stated Advantages
Reendothelialization is enhanced when endothelial cells or endothelial progenitor cells are perfused antegrade and retrograde compared with perfusion using only antegrade or only retrograde with the same number of cells.
Reduced thrombogenesis in the recellularized mammalian tissue or organ after transplantation when reendothelialized with antegrade and retrograde perfusion compared with corresponding tissue or organ reendothelialized antegrade or retrograde with the same amount of cells.
Reduced immunogenicity in the recellularized mammalian tissue or organ after transplantation when reendothelialized with antegrade and retrograde perfusion compared with corresponding tissue or organ reendothelialized antegrade or retrograde with the same amount of cells.
Documented Applications
Ex vivo reendothelialization of perfusion decellularized mammalian tissue or organ matrices.
Reducing thrombogenesis and immunogenicity in a recellularized mammalian tissue or organ following transplantation into a mammalian recipient.
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