Monday, July 20, 2015

The microRNA in tissue regeneration

I found a very interesting article that provides a concise literature review with 80 papers about original research in translational medicine .

The polymeric molecules that are the subject of discussion today are the microRNAs ( miRNA ). They are perfect complements to the target messengerRNA ( mRNA ) in plant cells , but they slightly mismatch in base pairing inside animal cells . The gene regulation using the complex micro RNA - m RNA triggers a wide variety of cellular mechanisms .

The cellular mechanisms that achieve organ regeneration , in a spatiotemporally controlled manner , are the differentiation , the dedifferentiation , the transdifferentiation , and the cellular proliferation . They alter the cellular plasticity .

The researchers learn from the invertebrates , the lower vertebrates , and the mammals how to activate the pluripotent stem cells in order to regrow parts or the entire organism . The trigger for the chain of events in the regeneration process is either the under - or the over - expression for the specific microRNA . The article provides a list for the microRNAs that regulate the human mesenchymal , and the human pluripotent ( the human embryonic , the human induced pluripotent ) stem cells .

The modulation of the regeneration process using microRNAs may be done by varying the modulators , the delivery method , or the cellular strategy ( figure 1 ) . The target cells are either the implanted or the endogeneous cells . The scientist may apply a modulation strategy on the endogenous ( stem ) cells , on the implanted cells prior to implantation , or on both the endogenous cells and the implanted cells . The modulators are either the cells themselves , the synthetic oligonucleotides , or the level of expression . The paper presents four delivery methods for the microRNAs : through direct injection , with viruses , with synthetic nanoparticles , and with cells as delivery vehicles .

Figure 1 . The technique variations for the micro - RNA signaling in the process of tissue regeneration .
Copyright ( 2014 ) AlphaMed Press

The heart has a limited potential for endogenous regeneration . The neonatal heart has a different response to myocardial infarction than the adult heart . The underexpressed microRNAs that trigger the proliferation of the cardiomyocytes are the miR - 15 family , the miR - 17 - 92 cluster , the miR - 199a and the miR - 590 families . They may help in the differentiation for the stem cells , for the cellular lineage commitment , and in the direct reprogramming process of the fibroblasts to generate cardiomyocytes . They are critical components in the signalling network for the adult cellular proliferation .

The microRNAs have a complex behaviour that is still not yet fully understood . The modulation strategy varies with the target organ that requires regeneration , and the research application .

References :

Frith J . E . , Porrello E . R . , Cooper - White J . J . ( 2014 )" Concise review : new frontiers in MicroRNA - based tissue regeneration " , Stem Cells Translational Medicine , 3 ( 8 ) , 969 - 976 .