Methods of recellularizing a tissue or organ for improved transplantability
Inventors
Taylor, Doris A • Kren, Stefan M.
Assignees
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Abstract
Described herein are methods of recellularizing an organ or tissue matrix.
Core Innovation
The claimed invention concerns ex vivo reendothelialization of a decellularized mammalian vascularized 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. This approach enhances reendothelialization relative to perfusing or receiving the same number of cells through only one direction. The described approach improves vascular coverage of the matrix, with [procedural detail omitted for safety].
The provided description identifies thrombogenesis and inflammation, alongside limited vascular coverage and transplantability, as concerns addressed by reendothelialization. Experimental evidence reports cell-seeded decellularized matrices having cellular structures, viable cells with endothelial functional markers, and increased relative thrombomodulin activity compared with matrix alone. Furthermore, G6PD activity remains near baseline over seven days, though the background problem is not explicitly described in the provided text.
Claims Coverage
The claims cover ex vivo reendothelialization of decellularized mammalian vascularized tissue or organ matrices, transplantation of the reendothelialized matrix, and reendothelialization of specified organ matrices, presenting three inventive features.
Antegrade and retrograde perfusion for enhanced reendothelialization
The claim covers ex vivo reendothelialization of a decellularized mammalian vascularized 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, enhancing reendothelialization relative to perfusion with the same number of cells in only one direction. Delivery involves [procedural detail omitted for safety].
Transplantation to reduce thrombogenesis and immunogenicity
The claim covers reendothelialization via antegrade and retrograde perfusion followed by transplanting the reendothelialized tissue or organ matrix into a recipient to reduce thrombogenesis and immunogenicity.
Reendothelialization of kidney, liver, lung, or pancreas matrices
The claim specifies an ex vivo method for reendothelializing a decellularized mammalian kidney, liver, lung, or pancreas matrix with endothelial cells or endothelial progenitor cells, with enhanced reendothelialization relative to a corresponding matrix receiving the same number of cells through one direction. Delivery involves [procedural detail omitted for safety].
The inventive features focus on bidirectional perfusion of endothelial cells or endothelial progenitor cells to enhance reendothelialization, transplantation to reduce thrombogenesis and immunogenicity, and reendothelialization of kidney, liver, lung, or pancreas matrices.
Stated Advantages
Enhanced reendothelialization compared with a corresponding decellularized matrix receiving or perfused with the same number of cells through only one direction.
Reduction of thrombogenesis and immunogenicity following transplantation of the reendothelialized tissue or organ matrix.
Documented Applications
Ex vivo reendothelialization of decellularized mammalian vascularized tissue or organ matrices, including kidney, liver, lung, and pancreas matrices.
Transplantation of a reendothelialized tissue or organ matrix into a recipient.
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