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-9433706-B2
Publication Date
2016-09-06
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 preparing an allogeneic or subject-derived bioengineered blood vessel by introducing whole blood comprising progenitor cells into the lumen of a tubular acellular scaffold and culturing the cells so they populate the scaffold to generate a bioengineered blood vessel. The acellular scaffold is a decellularized blood vessel, preserving extracellular matrix while removing nuclei and HLA, to support recellularization and reduce immunogenicity.
The recellularization approach includes seeding or delivery into the decellularized lumen and/or around the scaffold, with in vitro culture and perfusion using endothelial cell medium and smooth muscle cell medium in alternation. The alternation is repeated at least twice, and the vessel-recellularization outcome is characterized by endothelial-cell associated markers and smooth muscle-associated markers.
Endothelial characteristics are described using VE-cadherin, AcLDL, vWF, and CD31, while smooth muscle characteristics are described using smooth muscle actin and vimentin. A bioreactor configuration perfuses cells and media through the lumen and around the scaffold to support generation of the bioengineered blood vessel, with supporting characterization including retained ECM and growth factors, marker expression, tensile strength, graft patency, and reduced immunogenicity.
Claims Coverage
Independent claims clm-00001 and clm-00013 define two inventive features: introducing whole blood comprising progenitor cells into a tubular acellular scaffold and culturing the cells to populate the scaffold, and transplanting the prepared bioengineered blood vessel to a subject.
Whole blood introduced into scaffold lumen and cultured to populate
introducing whole blood comprising progenitor cells to the lumen of a tubular acellular scaffold and culturing said cells, wherein the cultured cells populate the scaffold to generate the bioengineered blood vessel
Subject provision of a bioengineered blood vessel graft by lumen loading, culturing, and transplantation
introducing subject-derived whole blood comprising progenitor cells to the lumen of a tubular acellular scaffold; culturing said cells on the lumen of the tubular acellular scaffold, thereby preparing the bioengineered blood vessel; and transplanting the bioengineered blood vessel to the subject
The claim coverage centers on lumen-based introduction of whole blood containing progenitor cells into a tubular acellular scaffold followed by culturing to populate the scaffold and form a bioengineered blood vessel, with the second independent claim further requiring transplantation of the prepared graft to a subject. Dependent claim refinements specify a decellularized blood vessel, injection or perfusion, in vitro culturing, alternating perfusion of endothelial and smooth muscle media repeated at least twice, and endothelial and smooth muscle marker expression.
Stated Advantages
Reduced immunogenicity as described by example observations regarding anti-endothelial cell antibodies and immunosuppression.
Preservation of extracellular matrix (ECM) and retained growth factors as described in characterization results.
Generation of endothelial and smooth muscle cell phenotypes indicated by marker expression (VE-cadherin, AcLDL, vWF, CD31; smooth muscle actin, vimentin).
Improved mechanical performance as described by tensile strength measurements and graft patency observations.
Documented Applications
Providing a bioengineered blood vessel graft to a subject in need thereof by preparing the graft and transplanting it to the subject.
Implantation/transplantation of the bioengineered blood vessel graft with example surgical or clinical data including graft patency and reduced immunogenicity.
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