University of Michigan

Yale University

Stephen G Emerson

Bernhard O Palsson

Michael F Clarke

R Douglas Armstrong

Mark Jay Shlomchik

Warren D Shlomchik

Russell S Taichman

The invention includes compositions and methods for depleting antigen presenting cells, or for impairing the biological function of antigen presenting cells, which compositions are useful for treatment of graft versus host disease and other immune diseases.

Prevention of immunoreactivity by depleting or inhibiting antigen presenting cells

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.

METHODS FOR REGULATING THE SPECIFIC LINEAGES OF CELLS PRODUCED IN A HUMAN HEMATOPOIETIC CELL CULTURE, METHODS FOR ASSAYING THE EFFECT OF SUBSTANCES ON LINEAGE-SPECIFIC CELL PRODUCTION, AND CELL COMPOSITIONS PRODUCED BY THESE CULTURES

Methods, including culture media conditions, which provide for ex vivo 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 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.

Methods and compositions for the ex vivo replication of stem cells, for the optimization of hematopoietic progenitor cell cultures, and for increasing the metabolism, GM-CSF secretion and/or IL-6 secretion of human stromal cells

Methods, compositions and devices are provided for the growth of human stem and/or hematopoietic cells in culture. Bioreactors are provided in which diverse cell types are simultaneously-cultured in the presence of appropriate levels of nutrients and growth factors substantially continuously maintained in the bioreactor while removing undesirable metabolic products. This simultaneous culture of multiple cell types successfully reconstructs hematopoietic tissue ex vivo. Optionally, at least one growth factor is provided through excretion by transfected stromal cells, particularly heterologous cells. The invention also allows for the separate maintenance of stromal and hematopoietic cells, and to allow for harvesting of both the adherent and non-adherent cells.

Devices for maintaining and growing human stem and/or hematopoietics

Methods, compositions and devices for maintaining and growing human stem

Processes, compositions and uses of hematopoietic cells are disclosed. Hematopoietic cells are cells which can differentiate into mature blood cells when co-cultured with osteoblasts. Specifically, a process for propagating and maintaining the immature morphology of a hematopoietic cell by co-culturing with osteoblasts is disclosed. The osteoblasts provide cytokines and/or a microenvironment which propagates and maintains the immature morphology of a hematopoietic cell. Hematopoietic cells are useful in the treatment of certain blood related disorders and are useful for treatment of patients in need of hematopoietic cells.

Hematopoietic cells: compositions and methods

Compositions containing cultured mitotic human stem cells

Methods, including culture media conditions, which provide for ex vivo human stem cell division and stable genetic transformation 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 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.

Methods and compositions for the ex vivo replication of human

Methods for the ex vivo replication of human stem cells and/or expansion

Methods for regulating the specific lineages of cells produced in a

Methods, compositions and devices are provided for the growth of hematopoietic cells in culture. Bioreactors are provided in which diverse cell types are simultaneously cultured in the presence of appropriate levels of nutrients and growth factors substantially continuously maintained in the bioreactor while removing undesirable metabolic products. This simultaneous culture of multiple cell types is required for the successful reconstruction of hematopoietic tissue ex vivo. At least one growth factor is provided through excretion by transfected stromal cells, particularly heterologous cells. Means are provided for maintaining the stromal cells and hematopoietic cells separately, to allow for early removal of the hematopoietic cells.

Methods, compositions and devices for growing human hematopoietic cells

Devices are provided for the growth of human stem and/or hematopoietic cells in culture. Bioreactors are provided in which diverse cell types are simultaneously-cultured in the presence of appropriate levels of nutrients and growth factors substantially continuously maintained in the bioreactor while removing undesirable metabolic products. This simultaneous culture of multiple cell types successfully reconstructs hematopoietic tissue ex vivo. Optionally, at least one growth factor is provided through excretion by transfected stromal cells, particularly heterologous cells. The stromal cells and hematopoietic cells are maintained separately and both the adherent and non-adherent cells are harvested.

Growing community of inventors

Ann Arbor, MI, United States of America

Stephen G Emerson