Bioengineered allogeneic blood vessel
Inventors
Sumitran-Holgersson, Suchitra • Olausson, Michael
Assignees
Olausson - Partial Interest (entire Interest Owned By Novahep Michael Olausson) Michael AB • Verigraft AB
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Publication Number
US-9090879-B2
Publication Date
2015-07-28
Expiration Date
Abstract
The present invention relates to methods for recellularization of blood vessels. This method is particularly useful for producing an allogeneic vein, wherein a donor vein is decellularized and then recellularized using whole blood or bone marrow stem cells. The allogeneic veins produced by the methods disclosed herein are particularly advantageous for implantation or transplantation into patients with vascular diseases.
Core Innovation
The invention relates to methods for recellularizing a blood vessel using a decellularized blood vessel scaffold and whole blood. The method introduces whole blood comprising endothelial cells, smooth muscle cells, and/or progenitor cells for endothelial and smooth muscle cells into the lumen of the decellularized blood vessel and then culturing the cells on the decellularized blood vessel to thereby recellularize the blood vessel.
In certain embodiments, the recellularization is carried out with media-based culturing using endothelial cell medium and smooth muscle cell medium with alternation of perfusion conditions. The described approach includes endothelial and smooth muscle cell recellularization outcomes in which endothelial cells localize to line the lumen and smooth muscle cells localize in vessel media and/or vessel walls, with endothelial and smooth muscle cells expressing named markers.
In further embodiments, the recellularized blood vessel is provided as a blood vessel graft to a patient by transplanting the recellularized blood vessel into the patient. The described system is supported by decellularization efficacy using removal of nuclei and HLA class I/II, preservation of extracellular matrix and retained angiogenic factors, successful marker-positive recellularization and localization, and follow-up evidence of graft patency in treated patients, together with an example of anti-endothelial antibody screening showing no detected alloantibodies in a described case.
Claims Coverage
The document contains two independent methods. Across the independent claims, the inventive features are centered on recellularizing a decellularized blood vessel with whole blood delivered to the vessel lumen and cultured on the scaffold, and using the resulting recellularized blood vessel as a graft by transplanting it into a patient.
Whole blood delivery to a decellularized blood vessel lumen and culturing on the decellularized vessel
Introducing whole blood comprising endothelial cells, smooth muscle cells, and/or progenitor cells for endothelial and smooth muscle cells to the lumen of a decellularized blood vessel, and culturing said cells on the decellularized blood vessel, thereby recellularizing the blood vessel.
Patient graft provision using a recellularized blood vessel prepared from patient-derived whole blood
Delivering patient-derived whole blood comprising endothelial cells, smooth muscle cells, and/or progenitor cells for endothelial and smooth muscle cells to the lumen of a decellularized blood vessel; culturing said cells on the decellularized blood vessel, thereby recellularizing the blood vessel; and transplanting the recellularized blood vessel into the patient.
The independent claims cover recellularization of decellularized blood vessel lumens using whole blood and subsequent culturing to generate endothelial and smooth muscle populations, and they further cover transplanting the recellularized vessel into a patient as a graft. Dependent claims refine the approach with alternation of endothelial cell medium and smooth muscle cell medium perfusion, repetition of the alternation at least twice, selection or sourcing of the decellularized vessel, delivery mode, and specific expression marker requirements for endothelial and smooth muscle cells.
Stated Advantages
Availability of a blood vessel scaffold and reduced need for immunosuppression.
Preservation of natural ECM and growth-factor retention (angiogenic growth factors retained).
Successful recellularization with endothelial and smooth muscle cell localization and marker expression.
Recovery of mechanical/tensile strength.
Demonstrated graft patency evidence in follow-up imaging after implantation.
Anti-endothelial antibody screening showing no detected alloantibodies in a described case.
Documented Applications
Providing a blood vessel graft to a patient by transplanting a recellularized blood vessel.
Implantation/transplantation of treated recellularized blood vessels into patients, with follow-up imaging evidence of graft patency.
Use of decellularized vein/artery scaffold recellularized ex vivo for regeneration of endothelial and smooth muscle cells for a graft context.
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