This work, by Sílvia Magalhães-Novais and led by Paulo Oliveira and Ignacio Vega-Naredo (former CNC researcher and currently professor at the University of Oviedo), was published in scientific journal Autophagy, one of the most renowned in the area. The main goal of the study was to try to understand how the autophagy (“recycling of cell components”) and apoptosis (“programmed cell death”), responsible for the quality control in numerous tissues, could increase stem cell competence, which have a crucial function in originate various cells in our body. This study might have a big impact in regenerative medicine, since it suggests strategies to keep the stem cells in our tissues healthy for longer.
“All our tissues have a pool of stem cells, that is gradually lost during aging. These cells have to possess a quality control system and resistance against unfavorable conditions, so they keep being viable and with the ability to replace differentiated cells that are gradually lost”, refers Paulo Oliveira, CNC researcher. “As we age, these pools empty out, as they also lose their ability to generate correct differentiated cells, accumulating errors in the process. If we understand how these stem cells keep their quality, namely, the recycling of the accumulated debris, or a healthy metabolism, we may preserve their tissue regenerative function. We wanted to understand how we could minimize the transmission of damage for the next cells, and guarantee a perfect copy”, describes.
In this study, initiated in 2009, the researchers used embryonic carcinoma stem cells as a study model. These cells have the ability to differentiate in many cell types, from cardiac to neuronal cells. Researchers used two cell populations: one population had its stemness kept, while the other was differentiated chemically induced. They observed that as cells differentiated – similarly to aging – they lost their recycling processes, accumulating harmful debris.
“This cell line is some sort of “dark side of the force” of stem cells, as it is derived from an embryonic carcinoma, but that allows us to observe the differentiation process in detail. When we observed these events in both populations, we saw higher accumulation of debris in cells, and more defected components, as mitochondria, our powerplants, in differentiated cells”, refers Paulo Oliveira. “When we stopped this recycling in non-differentiated cells, we saw that they would differentiate alone. We could understand that the quality control processes in these cells are more primed, and these quality control processes (by both autophagy and apoptosis) have a necessary role in metabolism and cell functions. In the future we would like to evaluate how other of these quality processes in cells are affected with differentiation, and how this other knowledge could be applied in regenerative medicine. Another path is doing this same evaluation in tumor cells, as these also possess great similarities with the stem cells we used in our study”, concludes.
Future studies will then try to evaluate if the detection and error correction of DNA is also lost in the differentiation, and how this could be applied to increase the tissue pools of stem cells. To understand how these processes will be similar to tumor cells, explaining their resistance to chemotherapeutic agents, is another future goal of these researchers.
Other than Sílvia Magalhães-Novais, Paulo Oliveira e Ignacio Vega-Naredo, the team of CNC researchers also had the participation of Rute Loureiro, Kátia Mesquita e Inês Baldeiras.
This study was financed by the Portuguese Funding Agency for Science and Technology (FCT), the European Fund for Regional Development (FEDER) COMPETE 2020, in the Cancel Stem project, by Instuto de Salud Carlos III and by Instuto de Investigación Sanitaria del Princiopado de Asturias (both from Spain). This study may be read wholly in: https://doi.org/10.1080/15548627.2019.1607694