Method to manufacture a cell preparation and such manufactured cell preparations
OwnerJoerg Gerlachinventor
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Abstract
This invention pertains to a method for the manufacturing of a cell preparation as well as such manufactured cell preparations. As a special form of such a cell preparation it also pertains to methods of generating organ/cell transplants and such a generated organ/cell transplants as well as subsequent applications. Such cell preparations are of interest for extracorporeal support systems, such as liver support, or transplants/cell implants that are transferred into organs, for instance the liver, or are placed in various other areas of an organism.
Claims86
Method to manufacture cell preparations thereby characterized that an unfractionated cell mixture of an organ or tissue is generated and the cells with a predetermined degree of maturity and/or differentiation are selectively and/or partially damaged.
Method according to above described claim thereby characterized that the damaging of the matured, highly differentiated cells occurs before, simultaneously with, or after the generation of the unfractionated cell mixture.
Method according to one of afore described claims thereby characterized that cells with a pre-determined degree of impairment and/or a predetermined degree of maturation and/or—differentiation are extracted from the cell preparation.
Method according to one of afore described claims thereby characterized that the cell preparation is maintained under culture conditions for proliferation, differentiation, and/or maintenance.
Method according to one of afore described claims thereby characterized that the cells are taken into co-culture with other differentiated cells of the same and/or another defined organ- and/or tissue type (of an organ and/or tissue) of the same and/or another organism before, simultaneously with, or subsequent to selective and/or partial damage.
Method for the production of a cell preparation thereby characterized that one or several stem cells are cultivated in co-culture with other differentiated cells of a pre-determined organ and/or tissue.
Method according to one of afore described claims thereby characterized that the stem cells are maintained in co-culture under culture conditions with other differentiated cells of the same and/or another pre-determined organ, and/or pre-determined tissue type (of an organ, and/or tissue) of the same and/or another organism for proliferation, differentiation, and/or maintenance.
Method according to afore claim thereby characterized that a barrier is used that is permeable or semi-permeable for active agents, mediators, and/or metabolic products of cells.
Method according to one of the two afore described claims thereby characterized that a membrane not permeable for cells, for example a hollow fiber or flat membrane, is used as barrier.
Method according to above described claim thereby characterized that a membrane is used that exhibits pores which facilitate cell-cell communication.
Method according to one of afore described claims thereby characterized that following the selective and/or partial damage of the cells, non-parenchymal and/or mesenchymal cells of the same and/or another organ and/or tissue type of the same and/or another organism are added.
Method according to one of afore described claims thereby characterized that bio-matrix proteins, e.g. collagens or fibronectin, are added to the cell preparation.
Method according to one of afore described claims thereby characterized that the cell preparation is cultivated before, simultaneously with, and/or after the selective and/or partial damage in an organ- and/or tissue specific environment.
Method according to one of afore described claims thereby characterized that the cell preparation is cultivated in a module. The module consists of an outer casing, and at least three independent membrane systems, whereby at least two independent membrane systems are designed as hollow fiber membranes and are arranged in the interior of the module. These hollow fiber membranes form a tightly packed network. The cells are arranged inside the hollow spaces of the network and/or adhere to the hollow fiber membranes (3). This network, consisting of intersecting and/or overlaying hollow fiber membranes, is constructed in such a way that the cells have almost identical substrate supply and removal conditions from anywhere inside the module (1).
Method according to one of afore described claims thereby characterized that the cell preparation is cultivated inside a module, consisting of a body made of porous material whose pores communicate with each other, and at least one channel like hollow pathway system whose hollow pathways intersect and/or overlay each other, penetrate the body, and is arranged inside a water-/germ tight container.
Method according to one of the afore described claims thereby characterized that the cell preparation is cultivated in at least one bioreactor in the form of a perfuseable organ copy consisting of an immunological inactive porous body, whose pores communicate with each other, and organ specific hollow structures.
Method according to one of afore described claims thereby characterized that the stem cell preparation is stored cooled or frozen.
Method according to one of afore described claims thereby characterized that before and/or after selective and/or partial damage, the regeneration, proliferation and/or differentiation of the cells is stimulated through the addition of active agents, growth factors, and/or differentiation factors.
Cell preparation containing an unfractionated cell mixture of an organ and/or tissue thereby characterized that the cells with a predetermined degree of maturity and/or differentiation are selectively and/or partially damaged.
Cell preparation according to afore described claim thereby characterized that the cells were damaged before, simultaneously with, or after the generation of the unfractionated cell mixture.
Cell preparation according to one of the two afore described claims thereby characterized that the cells with a predetermined degree of damage and/or a predetermined degree of maturity and/or degree of differentiation are separated and extracted from the cell preparation.
Cell preparation containing a culture of stem cells thereby characterized that it contains additional differentiated cells of a predetermined organ and/or tissue.
Cell preparation according to afore claim thereby characterized that it contains other additional differentiated cells of the same and/or another specific organ and/or tissue type of an organ and/or tissue of the same and/or another organism.
Cell preparation according to afore described claim thereby characterized that the barrier is permeable or semi-permeable for active agents and/or metabolic products of cells.
Cell preparation according to one of the two afore described claims thereby characterized that the barrier is a membrane not permeable for cells.
Utilization of a process or a cell preparation according to one of afore described claims for the production of a stem cell culture, a progenitor cell culture, or a stem cell culture of a mammal or a human.
Utilization according to afore described claim for the generation of a culture of somatic stem cells.
Utilization according to one of the two afore described claims for the generation of a stem cell culture of an organ and/or tissue.
Utilization according to afore described claim for the generation of an organ specific stem cell culture from liver, bone marrow, lymph nodes, thymus, spleen, kidney, pancreas, pancreatic islet organ, mucosa membrane, thyroid gland, parathyroid gland, adrenal gland, bone, gonads, uterus, placenta, ovaries, blood vessels, heart, lungs, muscle, intestinal wall, bladder, heart muscle, brain, neural tissue, and/or other mammalian organs.
Method, according to afore described claims, for the production of an autologous organ transplant for transplantation into a patient thereby characterized that a homologous organ transplant is infused with the patient's own cells, and the original cells of the organ transplant are selectively and/or partially damaged.
Method according to afore described claim thereby characterized that the patient's own cells consist of an unfractionated cell mixture.
Method according to afore described claims thereby characterized that the original material stems from fetal cells, including human fetal cells.
Method according to afore described claims thereby characterized that the original material stems from stem cell lines or embryonal stem cells, including human embryonal cells.
Dependencies are inferred from the claim text.