Canine Embryonic Stem Cells
The establishment of embryonic stem (ES) cell lines has brought great promise and opportunities for regenerative medicine and pharmaceutical research. Embryonic stem cells are derived from embryonic sources and are pluripotent i.e. they possess the capability of developing into a wide variety of different cell types, and tissues and organs.
Procedures for the development of embryonic stem cell lines for different species poses challenges due to differences in the pattern of embryonic development in different species. Different strategies are required in order to prepare embryonic stem cells from a particular species. Pluripotent embryonic stem cell lines have been derived from preimplantation embryos of mice. Pluripotent embryonic stem cell lines have also been described for primates and humans. To date, there have been no reports for the establishment of canine embryonic cells or cell lines.
Our researchers were able to define conditions for isolation of embryos and stem cells from canines and for establishing canine embryonic stem cells and cell lines. More particularly, our researchers identified appropriate culture conditions and determined embryonic developmental stages that enable maintenance and expansion of canine embryonic stem cells.
This invention provides cells exhibiting a canine embryonic stem cell phenotype, and cell lines comprising cells exhibiting a canine embryonic stem cell phenotype.
This provides a purified preparation comprised or enriched for canine embryonic stem cells that are capable of indefinite proliferation in vitro in an undifferentiated state. A preparation of canine embryonic stem cells may also be characterized by being immunoreactive with markers for embryonic stem cells, preferably canine embryonic stem cells. These stem cells express genetic markers of canine embryonic stem cells, including but not limited to Oct-4, SSEA-4, SSEA-1, TRA-1-60, and alkaline phosphatase.
Cells from the cell preparations may be introduced into a blastocyst or aggregated with an early stage embryo to produce chimeric conceptuses. A chimeric conceptus may be allowed to grow to term, or sacrificed during gestation to observe the contribution of the stem cell line. The conceptuses can be engineered to carry selectable markers or genetic alterations. Cells of the invention may be used to repopulate an embryo of the same species thus giving rise to a chimeric animal, particularly a chimeric animal in which some or all of the germ cells are derived from the cultured cells. The embryonic stem cells may have been genetically modified or selected for genetic modification in culture.
The invention can provide for the derivation of canine embryonic stem cells from embryos carrying a particular genetic background or specific mutations. For example, the embryos can be derived from high-pedigree canines.
The cells, cell lines, cell preparations, chimeric conceptuses, embryos and chimeric animals of the invention may be used to screen for potential therapeutics that modulate development or activity e.g. proliferation. The cells and cell preparations of the invention may be used to prepare model systems of disease conditions.
The technology may be used to produce additional copies of essential genes to allow augmented expression by cells of certain gene products in vivo. These genes can be, for example, hormones, matrix proteins, cell membrane proteins, cytokines, adhesion molecules, or "rebuilding" proteins important in tissue repair.
The cell preparations and compositions can be used in a variety of methods (e.g. transplantation) and they have numerous uses in the field of medicine. They may be used for the replacement of body tissues, organs, components or structures which are missing or damaged due to trauma, age, metabolic or toxic injury, disease, idiopathic loss, or any other cause.
Patent applications have been filed in the United States, Canada, Europe and Japan.
The Innovations Group is looking for a licensing partner (Animal Health or Pharma/Biotech) with expertise in exploiting embryonic stem cell technologies.
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