En vivo generated tissue system
Inventors
Noll, Lee • Hampson, Brian • Goltry, Kristin • Snabes, Samantha
Assignees
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Publication Number
US-8778330-B2
Publication Date
2014-07-15
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 relates to an ex vivo tissue-like bioreactor system for continuous long-term production and output of cells or tissues. The system generates an ex vivo matrix of cells that mimics at least one phenotype of a naturally occurring mammalian tissue by arranging cells on a 3D cell-matrix, and the matrix material is configured to receive cells in a fluid and supports formation of tissue-like structures.
The bioreactor comprises a fluid chamber for flowing the first fluid including the cells to the matrix material, together with gas delivery that uses a gas-permeable membrane operably linked to a gassing chamber. The description emphasizes decoupled gas and nutrient delivery and maintaining cell microenvironment gradients, including nutrients, oxygen, pH, waste byproducts, and growth or signaling factors, to promote cell organization on the matrix.
The fluid flow arrangement includes selectable flow paths such as parallel or cross-flow and single-pass versus recirculation, with diffusion gradients and shear control as part of maintaining the microenvironment. The system provides the ex vivo generated matrix of cells to a patient to provide a therapeutic benefit, and in another implementation includes harvesting cells released into the culture medium followed by providing the harvested cultured cells to the patient.
Claims Coverage
The disclosure supports two independent claims directed to methods of providing a therapeutic benefit to a patient using ex vivo generation of a cell-matrix in a bioreactor with a gas-permeable membrane linked to a gassing chamber. Across the independent claims, the inventive concept includes a bioreactor that combines a matrix material with fluid flow and linked gas delivery to maintain culture conditions that cause cells to arrange on the matrix to mimic a naturally occurring mammalian tissue phenotype.
Ex vivo cell-matrix that mimics naturally occurring tissue phenotype
Generating, ex vivo, a matrix of cells that mimics at least one phenotype of a naturally occurring mammalian tissue, by arranging stem cells, progenitor cells, mature cells, or a mixture of these on the matrix material in a bioreactor under conditions suitable for the cells to arrange so that they mimic at least one phenotype.
Bioreactor with matrix receiving cells in a first fluid and a chamber that flows the first fluid to the matrix
Providing a bioreactor comprising a matrix material configured to receive cells in a first fluid and a first chamber configured to flow the first fluid including the cells to the matrix material.
Gas-permeable membrane linked to a gassing chamber for gas delivery to the first fluid
Providing a first gas permeable membrane configured to permit a first gas to flow therethrough to the first fluid in the first chamber, and a gassing chamber operably linked to the first chamber, wherein the gassing chamber provides gas that flows through the first gas permeable membrane.
Providing the ex vivo generated matrix of cells to the patient for therapeutic benefit
Providing the ex vivo generated matrix of cells to the patient to provide a therapeutic benefit thereto.
Harvesting released cultured cells and providing harvested cells to the patient
Harvesting the cells which are released into the culture medium and providing the harvested cultured cells to the patient to provide a therapeutic benefit thereto.
Both independent claims cover therapeutic methods that generate an ex vivo cell-matrix in a bioreactor such that cells arrange on a matrix material to mimic at least one phenotype of naturally occurring mammalian tissue, using a fluid-flow chamber and a gas-permeable membrane operably linked to a gassing chamber for gas delivery to the first fluid. One claim provides the ex vivo generated matrix of cells to the patient, while the other additionally requires harvesting released cultured cells from the culture medium prior to providing them to the patient.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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