Sunday, November 18, 2007

HOLY GRAIL in THERAPEUTIC CLONING


-Top drawing : Taken from NYTimes.
- READ: SEMINAL PAPER of YAMANAKA, et al (Cell:/Nov/20/2007).
- SEE: Beating cardiomyocites derived from Human iPS cells.



Top: Teratoma derived from iPS cells. Several types of tissues. Down: generation of iPS cells. Introducing 4 factors (Oct3/4, Sox2, Klf4, and c-Myc) into mouse fibroblasts, pluripotent iPS cells are established. With 3 factors devoid of Sox2, nullipotent cells are generated.




We said in a previous article that cloning of the sheep Dolly and the recent of primates, had 2 hard obstacles a): require 278 and 302 intents (too many), respectively. And that some scientists rationalizing this misfortune, spoke of asynchronies among the generated eggs (modified genetically) and the uterine enviromments (and cycles), of female subrrogates animals, where they were implanted. b) to work with wrong ideas. But than lab asynchronies, the problem was of conception. It was thought outside of the target area (the own egg genetically modified, the same nucleus subject to a stressing and necessary reprogrammation). A biological theory, assures that all embryonic or mature differentiated cell (renal, liver, heart, neural, etc), are in principle, a clone of the stem cell that originate them. Except that to complete their specialized functions, some genes are silenced, other are not played and/or other genes are activated. The works of Shinya Yamanaka (45 years. Institute for Frontier Medical Sciences, Kyoto University/Japan), a former orthopedic surgeon specialized in genetic reprogramming has achieved by means of a simple and practical work, to place the scientific community, closer of human therapeutic clonatión (generation of tissues starting from the affected human's own cells), without the danger of immune rejection, useful tissues to replace deteriorated areas, aged or dead (in cases of Diabetes type 1, Parkinson´s disease, injuries to the spinal cord, heart inadequacy, burns, osteoporosis, etc), when restoring to the normality to those affected, prolonging his useful lives. In what we consider candidate number one to become the scientific breakthrough of the year, Yamanaka and his team reverted fibroblastic/differentiated mature cells of mice to their embryonic state. Using retrovirus to insert deliver genes in fibroblastic cells of mice, Yamanaka and his team selected 4 active genes (Oct3/4, Sox2, c-Myc, and Klf4, of a total of potentials 24), transforming the fibroblasts in stem cells (induced pluripotent stem cells: iPS) that exhibit genetic, growth and physical characteristics of typical embryonic stem cells. Yamanaka doesn't transfer nuclei, doesn't use human embryos, his technique is accepted socially and it doesn't fight with the world ethical committees. The work has been so overwhelming that forced immediately to Ian Wilmut (creator of the sheep Dolly), to abandon his projects (totally old fashioned), of creating human clones by means of simple nuclear transfer coming from differentiated cells to not fertilized eggs. Yamanaka has demonstrated that pluripotency usually reserved to embryonic stem cells is a démodé dogma. Before being rehearsed these techniques in human beings, obviously they should be improved, as long as the gene c-Myc, is implied in certain types of human cancers.

EXCELENCIA en CLONACION TERAPEUTICA.

Comentabamos en un articulo anterior que la clonación de la oveja Dolly y la reciente de primates, tenia 2 obstáculos insalvables a) : requerír 278 y 302 intentos (demasiados), respectivamente. Y, que algunos cientificos racionalizando la desventura, hablaban de asincronias entre los huevos generados (modificados genéticamente) y los ambientes (y ciclos), uterinos de las animales hembras subrrogadas, donde eran implantados. b) trabajar con ilaciones erróneas. Mas que asincronias laboratoriales, el problema era conceptual y de ilogicidad. Se conceptualizaba fuera del área implicada (el propio huevo genéticamente modificado, el mismo nucleo sujeto a una estresante y necesaria reprogramación). Una teoria biológica, asegura que toda celula diferenciada embrionaria o adulta (renal, hepática, cardiaca, neural, etc), es en principio, un clon de la celula madre que la origino. Excepto que para cumplir sus funciones especializadas, se silencian genes en unas, no se tocan en otras y/o se activan otros genes. Los trabajos de Shinya Yamanaka (45 años. Institute for Frontier Medical Sciences, Kyoto University/Japan), un ex cirujano ortopédico especializado en reprogramacion genética ha logrado mediante un trabajo sencillo y practico, colocar a la comunidad científica, a un paso de la clonación terapéutica (generación de tejidos a partir de las propias células del humano afectado), sin el peligro del rechazo inmune, tejidos utiles para reemplazar areas deterioradas, envejecidas o muertas (en casos de Diabetes tipo 1, enfermedad de Parkinson, injurias a la medula espinal, insuficiencia cardiaca, quemaduras, osteoporosis, etc), al restaurar a la normalidad a los afectados, prolongando sus vidas útiles. En lo que consideramos candidato de fuerza a evento (breakthrough), cientifico del año, Yamanaka y su equipo revirtieron células fibroblasticas/diferenciadas de ratones adultos a su estado embrionario. Empleando retrovirus para insertar genes en células fibroblasticas de ratones, Yamanaka y su equipo seleccionaron 4 genes activos (Oct3/4, Sox2, c-Myc, and Klf4, de un total de 24 potenciales), transformando los fibroblastos en células madre (induced pluripotent stem cells :iPS), que exhiben caracteristicas genéticas, físicas y de crecimiento, típicas de celulas madre embrionarias. Yamanaka no transfiere nucleos, no usa embriones humanos, su técnica es aceptada socialmente y no se pelea con los comités éticos mundiales. El trabajo ha sido tan contundente que obligó de inmediato a Ian Wilmut (creador de la oveja Dolly), a abandonar sus proyectos (totalmente anticuados,ya), de crear clones humanos mediante simples trasferencias nucleares de células diferenciadas a huevos no fertilizados. Yamanaka ha demostrado que la pluripotencia normalmente reservada a las células madre embrionarias es un dogma demode. Antes de ensayarse estas técnicas en humanos obviamente deben ser depuradas, en tanto el gene c-Myc, esta implicado en algunos ciertos cáceres humanos.

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