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.
Chavez S.L., Meneses J.J., Nguyen H.N., Kim S.K., Pera R.A. (2008) Stem Cells Dev., 17, 535-546. Scholar google search
Li L., Baroja M.L., Majumdar A., Chadwick K., Rouleau A., Gallacher L., Ferber I., Lebkowski J., Martin T., Madrenas J., Bhatia M. (2004) Stem Cells, 22, 448-456. Scholar google search
Buzzard J.J., Gough N.M., Crook J.M., Colman A. (2004) Nat. Biotechnol., 22, 381-382. Scholar google search
Saksela E., Moorhead P.S. (1963) Proc. Natl. Acad. Sci. USA, 50, 390-395. Scholar google search
Draper J.S., Smith K., Gokhale P., Moore H.D., Maltby E., Johnson J., Meisner L., Zwaka T.P., Thomson J.A., Andrews P.W. (2004) Nat. Biotechnol., 22, 53-54. Scholar google search
Brimble S.N., Zeng X., Weiler D.A., Luo Y., Liu Y., Lyons I.G., Freed W.J., Robins A.J., Rao M.S., Schulz T.C. (2004) Stem Cells Dev., 13, 585-597. Scholar google search
Mitalipov S., Clepper L., Sritanaudomchai H., Fujimoto A., Wolf D. (2007) Stem Cells, 25, 581-588. Scholar google search
Allegrucci C., Wu Y.Z., Thurston A., Denning C.N., Priddle H., Mummery C.L., Ward-van Oostwaard D., Andrews P.W., Stojkovic M., Smith N., Parkin T., Jones M.E., Warren G., Yu L., Brena R.M., Plass C., Young L.E. (2007) Hum. Mol. Genet., 16, 1253-1268. Scholar google search
Min J.Y., Yang Y., Converso K.L., Liu L., Huang Q., Morgan J.P., Xiao Y.F. (2002) J. Appl. Physiol., 92, 288-296. Scholar google search
Singla DK., Hacker T.A., Ma L., Douglas P.S., Sullivan R., Lyons G.E., Kamp T.J. (2006) J. Mol. Cell. Cardiol., 40, 195-200. Scholar google search
Nussbaum J., Minami E., Laflamme M.A., Virag J.A.I., Ware C.B., Masino A., Muskheli V., Pabon L., Reinecke H., Murry C.E. (2007) FASEB J., 21, 1345-1357. Scholar google search
Kehat I., Kenyagin-Karsenti D., Snir M., Segev H., Amit M., Gepstein A., Livne E., Binah O., Itskovitz-Eldor J., Gepstein L. (2001) J. Clin. Invest., 108, 407-414. Scholar google search
Roy N.S., Cleren C., Singh S.K., Yang L., Beal M.F., Goldman S.A. (2006) Nat. Med., 12, 1259-1268. Scholar google search
Adewumi O., Aflatoonian B., Ahrlund-Richter L., Amit M., Andrews P.W., Beighton G., Bello P.A. et al. (2007) Nat. Biotechnol., 25, 803-816. Scholar google search
Cabrera C.M., Nieto A., Cortes J.L., Montes R.M., Catalina P., Cobo F., Barroso-Del-Jesus A., Concha A. (2007) Cell Biol. Int., 31, 1072-1078. Scholar google search
Drukker M., Katz G., Urbach A., Schuldiner M., Markel G., Itskovitz-Eldor J., Reubinoff B., Mandelboim O., Benvenisty N. (2002) Proc. Natl. Acad. Sci. USA, 99, 9864-9869. Scholar google search
Behfar A., Zingman L.V., Hodgson D.M., Rauzier J.M., Kane G.C., Terzic A., Puceat M. (2002) FASEB J., 16, 1558-1566. Scholar google search
Hodgson D.M., Behfar A., Zingman L.V., Kane G.C., Perez-Terzic C., Alekseev A.E., Puceat M., Terzic A. (2004) Am. J. Physiol., 287, H471-H479. Scholar google search
Drukker M., Katchman H., Katz G., Even-Tov Friedman S., Shezen E., Hornstein E., Mandelboim O., Reisner Y., Benvenisty N. (2006) Stem Cells, 24, 221-229. Scholar google search
Stojkovic M., Stojkovic P., Leary Hall V.J., Armstrong L., Herbert M., Nesbitt M., Lako M., Murdoch A. (2005) Reprod. Biomed. Online, 11, 226-231. Scholar google search
French A.J., Adams C.A., Anderson L.S., Kitchen J.R., Hughes M.R., Wood S.H. (2008) Stem Cells, 26, 485- 493. Scholar google search
Lonergan P., Rizos D., Gutierrez-Adan A., Fair T., Boland M.R. (2003) Reprod. Domest. Anim., 38, 259-267. Scholar google search
Gao S., Chung Y.G., Williams J.W., Riley J., Moley K., Latham K.E. (2003) Biol. Reprod., 69, 48-56. Scholar google search
Tecirlioglu R.T., Cooney M.A., Lewis I.M., Korfiatis N.A., Hodgson R., Ruddock N.T., Vajta G., Downie S., Trounson A.O., Holland M.K., French A.J. (2005) Reprod. Fertil. Dev., 17, 573-585. Scholar google search
Ildstad S.T., Wren S.M., Bluestone J.A., Barbieri S.A., Sachs D.H. (1985) J. Exp. Med., 162, 231-244. Scholar google search
Burt R.K., Verda L., Kim D.A., Oyama Y., Luo K., Link C. (2004) J. Exp. Med., 199, 895-904. Scholar google search
Priddle H., Jones D.R., Burridge P.W., Patient R. (2006) Stem Cells, 24, 815-824. Scholar google search
Alexander S.I., Smith N., Hu M., Verran D., Shun A., Dorney S., Smith A., Webster B., Shaw P.J., Lammi A., Stormon M.O. (2008) N. Engl. J. Med., 358, 369-374. Scholar google search
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. Scholar google search
Joffre O., Santolaria T., Calise D., Al Saati T., Hudrisier D., Romagnoli P., van Meerwijk J.P. (2008) Nature Med., 14, 88-92. Scholar google search
Yamazaki S., Inaba K., Tarbell K.V., Steinman R.M. (2006) Immunol. Rev., 212, 314-329. Scholar google search
Lee M.K., Moore D.J., Jarrett B.P., Lian M.M., Deng S., Huang X., Markmann J.W., Chiaccio M., Barker C.F., Caton A.J., Markmann J.F. (2004) J. Immunol., 172, 6539-6544. Scholar google search
Cleland J.G., Coletta A.P., Abdellah A.T., Cullington D., Clark A.L., Rigby A.S. (2007) Eur. J. Heart Fail., 9, 102-108. Scholar google search
Orlic D., Kajstura J., Chimenti S., Jakoniuk I., Anderson S.M., Li B., Pickel J., McKay R., Nadal-Ginard B., Bodine D.M., Leri A., Anversa P. (2001) Nature, 410, 701-705. Scholar google search
Murry C.E., Soonpaa M.H., Reinecke H., Nakajima H., Nakajima H.O., Rubart M., Pasumarthi K.B., Virag J.I., Bartelmez S.H., Poppa V., Bradford G., Dowell J.D., Williams D.A., Field L.J. (2004) Nature, 428, 664-668. Scholar google search
Abdel-Latif A., Bolli R., Tleyjeh I.M., Montori V.M., Perin E.C., Hornung C.A., Zuba-Surma E.K., Al-Mallah M., Dawn B. (2007) Arch. Intern. Med., 167, 989-997. Scholar google search
Maherali N., Sridharan R., Xie W., Utikal J., Eminli S., Arnold K., Stadtfeld M., Yachechko R., Tchieu J., Jaenisch R., Plath K., Hochedlinger K. (2007) Cell Stem Cell, 1, 55. Scholar google search
Wernig M., Meissner A., Foreman R., Brambrink T., Ku M., Hochedlinger K., Bernstein B.E., Jaenisch R. (2007) Nature, 448, 318-324. Scholar google search
Takahashi K., Tanabe K., Ohnuki M., Narita M., Ichisaka T., Tomoda K., Yamanaka S. (2007) Cell, 131, 861-872. Scholar google search
Yu J., Vodyanik M.A., Smuga-Otto K., Antosiewicz-Bourget J., Frane J.L., Tian S., Nie J., Jonsdottir G.A., Ruotti V., Stewart R., Slukvin I.I., Thomson J.A. (2007) Science, 318, 1917-1920. CrossRef Scholar google search
Park I.H., Zhao R., West J.A., Yabuuchi A., Huo H., Ince T.A., Lerou P.H., Lensch M.W., Daley G.Q. (2008) Nature, 451, 141-146. Scholar google search