Improving the repairing capacity of tissues could have obvious implications for regenerative medicine, including the treatment of
multiple pathologies and degenerative processes associated with ageing.
According to a recent research, a team from the Spanish National Cancer Research Center (CNIO) has shown that tissue damage is a relevant factor for cells to go back to an embryonic state.
‘The expression of the OSKM genes (OCT4, SOX2, KLF4 and MYC)) results in damage to the cells; accordingly, they secrete interlukin-6; the presence of this molecule induces the reprogramming of some neighboring cells.’
Published in the journal Science
, the technique is based on introducing a combination of four genes known as OSKM (for the initials of the genes, OCT4, SOX2, KLF4 and MYC), reverts adult cells to an embryonic-like state, and transforms them into pluripotent cells. However, there are several limitations to this process, such as a very low efficiency and the emergence of a particular type of tumor (known as teratoma), which make cell reprogramming incompatible with its potential clinical use.
Manuel Serrano and the Tumor Suppression Group at the CNIO have been working in this field for years. Their innovative approach led them to achieve cell reprogramming within a living organism (in this case, a mouse) in 2013, whereas,until then, reprogramming had been only reported using explanted cells out of the organism.
The team analyzed what happens in living tissues, when reprogramming is induced using OSKM. "The Yamanaka genes are inefficient inducing reprogramming or pluripotency in the highly specialized cells that constitute adult tissues," explained Lluc Mosteiro.
Her observations indicate that tissue damage plays a critical role by complementing the activity of the OSKM genes. This relationship between damage and reprogramming is mediated by a proinflammatory molecule, interleukin-6 (IL6). Without its presence, the OSKM genes are far less efficient inducing the reprogramming process.
These findings suggest the following sequence of events: the expression of the OSKM genes results in damage to the cells; accordingly, they secrete IL6; the presence of this molecule induces the reprogramming of some neighboring cells.
Having identified the essential role of IL6, Serrano, Mosteiro and the rest of the team are now working on various pharmacological approaches to enhance the reprogramming efficiency, which could help to improve the regeneration of damaged tissue even in the absence of the Yamanaka genes.