Somatic stem cells and the origin of cancer.

Most human cancers derive from a single cell targeted by genetic and epigenetic alterations that initiate malignant transformation. Progressively, these early cancer cells give rise to different generations of daughter cells that accumulate additional mutations, acting in concert to drive the full neoplastic phenotype. As we have currently deciphered many of the gene pathways disrupted in cancer, our knowledge about the nature of the normal cells susceptible to transformation upon mutation has remained more elusive. Adult stem cells are those that show long-term replicative potential, together with the capacities of self-renewal and multi-lineage differentiation. These stem cell properties are tightly regulated in normal development, yet their alteration may be a critical issue for tumorigenesis. This concept has arisen from the striking degree of similarity noted between somatic stem cells and cancer cells, including the fundamental abilities to self-renew and differentiate. Given these shared attributes, it has been proposed that cancers are caused by transforming mutations occurring in tissue-specific stem cells. This hypothesis has been functionally supported by the observation that among all cancer cells within a particular tumor, only a minute cell fraction has the exclusive potential to regenerate the entire tumor cell population; these cells with stem-like properties have been termed cancer stem cells. Cancer stem cells can originate from mutation in normal somatic stem cells that deregulate their physiological programs. Alternatively, mutations may target more committed progenitor cells or even mature cells, which become reprogrammed to acquire stem-like functions. In any case, mutated genes should promote expansion of stem/progenitor cells, thus increasing their predisposition to cancer development by expanding self-renewal and pluripotency over their normal tendency towards relative quiescency and proper differentiation.

Células madre adultas / Mature stem cells

Uno de los campos de la medicina que más expectativas ha levantado en los últimos años es la terapia celular con células madre. El aislamiento de células embrionarias humanas, la aparente e inesperada potencialidad de las células madre adultas y el desarrollo de la terapia génica nos lleva a imaginar un futuro esperanzador para un número importante de enfermedades actualmente incurables. A lo largo de las siguientes páginas vamos a tratar de dibujar el panorama de la investigación con células madre, con la descripción de los principales logros en este campo así como con algunas de las preguntas pendientes de responder. A pesar de las grandes expectativas, es fundamental que mantengamos un espíritu crítico y realista a la hora de analizar los avances científicos en esta área.

Células madre adultas / Mature stem cells

Uno de los campos de la medicina que más expectativas ha levantado en los últimos años es la terapia celular con células madre. El aislamiento de células embrionarias humanas, la aparente e inesperada potencialidad de las células madre adultas y el desarrollo de la terapia génica nos lleva a imaginar un futuro esperanzador para un número importante de enfermedades actualmente incurables. A lo largo de las siguientes páginas vamos a tratar de dibujar el panorama de la investigación con células madre, con la descripción de los principales logros en este campo así como con algunas de las preguntas pendientes de responder. A pesar de las grandes expectativas, es fundamental que mantengamos un espíritu crítico y realista a la hora de analizar los avances científicos en esta área. (AU)