Embryonic Stem Cells

The early mammalian embryo is composed of cells that have the potential to contribute to all tissue types in the body, a property termed pluripotency. As the embryo develops to blastocyst stage, it forms an outer cell layer and an inner cluster of cells referred to as the inner cell mass (ICM). The outer cells become the trophectoderm and ultimately the placenta. The ICM cells create all tissues in the body, as well as nontrophoblast structures that support the embryo. Embryonic stem cells are derived in vitro from the ICM. ES cells were successfully developed from mouse blastocysts in 1981.[4,5] ES cells contribute to all three germ layers in the developing fetus, proving that they are pluripotent, but ES cells fail to contribute to the trophectoderm, revealing that they are not totipotent. ES cells, when removed from feeder layers, begin to differentiate into multilayered differentiated structures called embryoid bodies. In addition to blastocyst injection, the in vivo developmental potential of ES cells can be tested by injecting ES cells into severe combined immunodeficient (SCID) mice.[6] Benign ter-atomas form where the cells are injected and contain tumors representing all three germ layers.

Embryonic stem cell criteria

Pluripotent cells do not all possess the same characteristics. Listed below are defining properties of mouse ES cells:

Stable diploid karyotype Clonogenic property

Ability to recover after freezing and thawing Ability to survive and proliferate in vivo indefinitely High telomerase activity Teratoma and embryoid body formation Chimera formation and germ line colonization Undifferentiated state

Adult Animal

Fetus

Blastocyst Stage Embryo

Adult Animal

Fetus

Blastocyst Stage Embryo

Embryonic Milk Line

Developmental studies Cell differentiation Toxicology testing

Cell and tissue therapy, transplantation

Tissue engineering

Cancer

Disease models

Enhanced prolificacy/reproduction Increased disease resistance Increased feed utilization and growth Bio-pharmaceuticals

Improved carcass composition Biomedical models

Increased milk production Xenotransplantation

Developmental studies Cell differentiation Toxicology testing

Cell and tissue therapy, transplantation

Tissue engineering

Cancer

Disease models

Enhanced prolificacy/reproduction Increased disease resistance Increased feed utilization and growth Bio-pharmaceuticals

Improved carcass composition Biomedical models

Increased milk production Xenotransplantation

Fig. 1 Sources and applications of stem cells. (View this art in color at www.dekker.com.)

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