Riken Centre LogoJust last week we presented an investigation claiming human embryonic stem (ES) cells and reprogrammed cells to be identical. Experts from the RIKEN Center for Developmental Biology supposedly uncover the reason for ES cells and induced pluripotent stem (iPS) cells to go through programmed cell death (apoptosis) when cultured in isolation. It has been suggested that understanding the benefits of cell therapy techniques can lead to potential treatments for debilitating degenerative diseases.

During procedures like subcloning a technique called cell dissociation for isolating cells is triggered. However, this technique possibly faces a major obstacle of effective stem cell research due to its damaging effects on human ES cells. Experts claim that 99% of human ES cells cultured in this way are destroyed due to an extensive apoptotic response which is not present in mouse ES cells.

Prior analysis revealed the inhibition of a protein termed as the Rho-associated kinase (ROCK) can decrease this rate of cell death by 30%. But mechanisms involved in this were probably not known. In order to determine the possible mechanism, scientists applied live-cell imaging. Imaging was supposedly put to use in the early phase of dissociation in human and mouse ES cells.

The outcome was that the mouse ES cells barely appeared to move and the human ES cells skipped about in a so-called ‘death dance.’ These cells seemed to quickly sprout finger-shaped bulges, called as blebs that continued to grow till the cells burst and died. This early-onset blebbing was apparently observed by the researchers. It is believed that the duration and severity of blebbing was not known before as to the hyperactivation of myosin, which is a type of protein causing cell motility.

The investigators affirmed this myosin hyperactivation, mediated by activation of the ROCK kinase to be the direct cause of apoptosis in dissociated human ES cells, and not the blebbing. Another protein known for its role in cell motility, Rac, was ascertained to get along with ROCK activation for influencing myosin hyperactivation resulting to cell death. The research seemingly reveals a comprehensive explanation of mechanisms controlling dissociation-induced apoptosis in human ES cells. The scientists also claim to have suggested a safer and more effective cellular therapy treatment for a range of debilitating degenerative diseases.

The research is published in Cell Stem Cell.