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AssigneeThe Regents of the University of Michigan
InventorsBernhard O. Palsson, R. Douglas Armstrong, Michael F. Clarke, Stephen G. Emerson
Estimating the term…
Methods, including culture media conditions, which provide for in vitro human stem cell division and/or the optimization of human hematopoietic progenitor cell cultures and/or increasing the metabolism or GM-CSF secretion or IL-6 secretion of human stromal cells and/or a method for assaying the effect of a substance or condition on a human hematopoietic cell population, and/or depleting the malignant cell or T-cell and B-cell content of a human hematopoietic cell population are disclosed. The methods rely on culturing human stem cells and/or human hematopoietic progenitor cells and/or human stromal cells in a liquid culture medium which is replaced, preferably perfused, either continuously or periodically, at a rate of 1 ml of medium per ml of culture per about 24 to about 48 hour period, and removing metabolic products and replenishing depleted nutrients while maintaining the culture under physiologically acceptable conditions. Optionally, growth factors are added to the culture medium. The disclosed culture conditions afford improved methods for bone marrow transplantation.
A method for controlling the lineage development in an in vitro human tissue system, comprising culturing human stem and/or progenitor cells in a liquid culture medium which is replaced at a rate of about 1 ml of medium per 1 ml of culture per about 24 to about 48 hours, and removing metabolic products and replenishing depleted nutrients, while maintaining said culture under physiologically acceptable conditions, and adjusting the concentration of hematopoietic growth factors to select for enhanced production of a desired cell type.
A method for assaying the effect of a substance or physical condition on a human hematopoietic cell mass, comprising culturing a first portion of said human hematopoietic cell mass, including dividing human stem cells and progenitor cells, in a liquid culture medium which is replaced, either continuously, periodically, or intermittently, at a rate of about 1 ml of medium per ml of culture per about 24 to about 48 hour period in the presence of said substance, and removing metabolic products and replenishing depleted nutrients while maintaining said culture under physiologically acceptable conditions, and comparing the compositional profile of the human hematopoietic cell mass to the profile of a second portion of said human hematopoietic cell mass cultured identically but in the absence of said substance or physical condition.
A functioning in vitro human tissue system, comprising (i) a chamber containing human hematopoietic cells, including dividing human hematopoietic stem cells and progenitor cells cultured in a liquid culture medium, wherein said chamber contains a surface for the attachment of adherent cells (ii) means for replacing, either continuously or periodically, said liquid culture medium at a rate of about 1 ml of medium per ml of culture per about 24 to about 48 hour period, (iii) means for exposing said liquid culture medium to an oxygen-containing gas, and (iv) means for removing metabolic products and replenishing depleted nutrients while maintaining said culture under physiologically acceptable conditions to thereby maintain a functioning, reconstructed in vitro bone marrow tissue.
In a method of bone marrow transplantation, comprising obtaining a tissue sample from a donor, culturing said tissue sample, and implanting said tissue sample in a donee, wherein the improvement is said culturing comprises culturing said tissue, which comprises a mass of human stem cells, in a liquid culture medium which is replaced, either continuously or periodically, at a rate of about 1 ml of medium per ml of culture per about 24 to about 48 hour period, and removing metabolic products and replenishing depleted nutrients while maintaining said culture under physiologically acceptable conditions.
Dependencies are inferred from the claim text.