Establishment of ES Cell Lines and Regenerative Medicine

Abstract

Stem cells are divided into three types. ES cells show most potent activities. It can be differentiate into many types of organs, such as liver, lung etc. Then umblical stem cells are known. It will support the growth of tissue and organs. The bone marrow stem cells can be differentiated to form many types of blood cells, and also be used for leukemia therapy. Even though stem cells and somatic cells are presenting different function, their genome structure should be the same. But gene action are most probably different at each steps. Then stem cell research provides further genetic and molecular biology research and also will open a evolutionary frontier clinical medicine. Establishment of human embryonic stem (ES) cell lines has opened great potential and expectation for regenerative medicine and tissue engineering, because many types of human cells could be produced by their unlimited growth and differentiation in culture. ES cell lines have been established from mouse blastocysts and used for gene targeting studies to produce mouse strains with specific genetic alterations. Such pluripotent stem cells show extensive ability to differentiate into many types of functional cells and thy also enable the production of chimeric mice, in which they can contribute to all tissues and organs including germ cells. Primate and human ES cell lines have been established from blastocysts of monkey and surplus human blastocysts from fertility clinics. They showed several differences compared to mouse ES cells, including a tendency to produce the trophectoderm lineage and a different expression pattern of surface antigens. This may reflect species-specific differences, or these primate ES cells could represent earlier stages of pluripotent cell development than mouse ES cells. Also, they show no response to the LIF and gp130 signals, which are widely used to repress spontaneous differentiation of mouse ES cell colonies. We have established several ES cell lines from blastocysts of the cynomolgus monkey. They can be maintained in culture as stem cell colonies, and also, they produce several differentiated cell types in culture. When such ES cells were transplanted into SCID mice, they produced teratomas containing many differentiated tissues (Suemori H, Tada T, Torii R, Hosoi Y, Kobayashi K, Imahie H, Kondo Y, Iritani A, and Nakatsuji N. Establishment of embryonic stem cell lines from cynomolgus monkey blastocysts produced by IVF or ICSI. Dev. Dynamics, 222, 273-279, 2001). The unlimited proliferation capacity of ES cells in culture and subsequent differentiation into various types of functional cells could be used for cell transplantation therapy. Promising results have been obtained so far, mostly by using mouse ES cells for cell types such as neuron, glia, cardiac muscle, hematopoietic cells, endothelial cells and insulin-producing pancreatic cells. Combination of these ES-derived cells and various aspects of the tissue engineering should greatly expand the therapeutic scope in the future.