Ex vivo generated tissue system
Inventors
Noll, Lee • Hampson, Brian • Goltry, Kristin • Snabes, Samantha
Assignees
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Publication Number
US-8394632-B2
Publication Date
2013-03-12
Expiration Date
Abstract
The present invention relates to methods of generating an ex vivo tissue-like system in a bioreactor system capable of supporting continuous production of, and output of cells and tissues and an ex vivo tissue system made therefrom.
Core Innovation
The invention describes a method of generating, ex vivo, a matrix of cells that mimics at least one phenotype of naturally occurring mammalian tissue. The method uses a bioreactor with matrix material positioned between first and second fluid flow paths, gas-permeable membranes, gassing chambers, and culture media. Cells arrange on the matrix material under conditions suitable to mimic the tissue phenotype, and the cells comprise stem cells, progenitor cells, mature cells, or mixtures thereof.
The problem being solved is not explicitly described in the patent content provided because background and summary sections are omitted. Microscopic documentation shows cell aggregates and fibrous structures associated with the matrix material, including cross-sections at varying magnifications. These images document cellular organization and coverage across the matrix material without presenting quantitative results.
Claims Coverage
The supplied relevant claims identify one independent claim, claim 1, comprising nine inventive features covering ex vivo cell matrix generation, bioreactor flow-path and gas-delivery arrangements, and associated dependent claim features.
Generation of a tissue-mimicking cell matrix
Claim 1 covers generating, ex vivo, a matrix of cells that mimics at least one phenotype of naturally occurring mammalian tissue.
Matrix material between two fluid flow paths
The matrix material is disposed between first and second flow paths, wherein the first fluid including cells flows tangentially to a surface of the matrix material.
Gas-permeable membranes and gassing chambers
The first and second chambers are operably linked to respective gassing chambers, and gas-permeable membranes permit gas to flow to the fluid in each chamber.
Cell arrangement under culture conditions
Culture media is provided to the bioreactor for a time and under conditions suitable for the cells to arrange on the matrix material and mimic at least one phenotype of naturally occurring mammalian tissue.
Tangential second flow path
A dependent claim specifies that the second flow path extends tangentially to the matrix surface in contact with the second fluid.
Harvesting while preserving culture integrity
A dependent claim specifies harvesting cells without disrupting the culture or its future progress.
Media recirculation and fluid handling
A dependent claim describes a connected device that recirculates media, permits waste removal and fresh media delivery, and uses fresh media, recirculated media, or both.
Culture access ports
A dependent claim describes ports for cell or media collection and introduction of cell culture additives without disturbing the culture.
Harvested cell mixture composition
A dependent claim specifies that harvested cells comprise a mixture of different cell types.
The independent claim centers on generating an ex vivo cell matrix mimicking a mammalian tissue phenotype using a matrix positioned between two fluid flow paths with gas delivery membranes and culture media. The dependent claims add features specifying flow orientation, culture-preserving cell harvesting, media recirculation, access ports, and heterogeneous cell mixtures.
Stated Advantages
The described experiments report that cross-flow shear increased harvested cell yields and altered hematopoietic lineage composition.
The described experiments report sustained production of over one million cells per harvest during a 376-day culture, with viable cell output.
Documented Applications
Generating ex vivo a matrix of cells that mimics at least one phenotype of naturally occurring mammalian tissue.
Supporting continuous cell or tissue output through the described perfusion bioreactor.
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