Abstract: Human embrional stem cells (hESC) are able to maintain pluripotency in culture, to proliferate indefinitely and to differentiate into any somatic cell type. Due to these unique properties, hESC may become an exceptional source of tissues for transplantation and have great potencial for the therapy of incurable diseases. Here, we review new developments in the area of embrional stem cells and discuss major challenges - standartization of protocols for cell derivation and cultivation, identification of specific molecular markers, development of new aprouches for directed differentiation etc. - which remain to be settled, prior to safe and successful clinical application of stem cells. We appraise several potential approaches of hESC therapy including derivation of autologous cells via therapeutic cloning (1), generation of immune tolerance to allogenic donor cells via hematopoetic chimerism (2), and development of the banks of hESC lines (3). In addition, we discuss brifly induced pluripotent cells, which are derived via genetic modification of autologous somatic cells and are analogous to ESC. Our analysis demonstrates that uncontrollable differentiation in vivo and teratogenic potential of hESC are critical limitations of their application in clinic. Therefore, the major direction of hESC use is derivation of a specific differentiated progeny, which has lower proliferative potential and immune privilege, yet poses fewer risks. Finally, cell therapy is far more complex and resource-consuming process as compared to drug-based medicine; pluripotent stem cell biology and technology is in need of further investigation and development before these cells can be used in clinics.
Reference: Borisenko G.G., The prospect of pluripotent stem cell-based therapy, Biomeditsinskaya khimiya, 2009, vol:
74. Kawai T., Cosimi A.B., Spitzer T.R., Tolkoff-Rubin N., Suthanthiran M., Saidman S.L., Shaffer J., Preffer F.I., Ding R., Sharma V., Fishman J.A., Dey B., Ko D.S., Hertl M., Goes N.B., Wong W., Williams W.W. Jr., Colvin R.B., Sykes M., Sachs D.H. (2008) N. Engl. J. Med., 358, 353-361.
75. Joffre O., Santolaria T., Calise D., Al Saati T., Hudrisier D., Romagnoli P., van Meerwijk J.P. (2008) Nature Med., 14, 88-92.