Introduction: One of the key factors that may influence the therapeutic potential of mesenchymal stem/stromal cells (MSCs) is their metabolism. The switch between mitochondrial respiration and glycolysis can be affected by many factors, including the oxygen concentration and the spatial form of culture. This study compared the metabolic features of adipose-derived mesenchymal stem/stromal cells (ASCs) and dedifferentiated fat cells (DFATs) cultivated as monolayer or spheroid culture under 5% O2 concentration (physiological normoxia) and their impact on MSCs therapeutic abilities. Results: We observed that the cells cultured as spheroids had a slightly lower viability and a reduced proliferation rate but a higher expression of the stemness-related transcriptional factors compared to the cells cultured in monolayer. The three-dimensional culture form increased mtDNA content, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), especially in DFATs-3D population. The DFATs spheroids also demonstrated increased levels of Complex V proteins and higher rates of ATP production. Moreover, increased reactive oxygen species and lower intracellular lactic acid levels were also found in 3D culture. Conclusion: Our results may suggest that metabolic reconfiguration accompanies the transition from 2D to 3D culture and the processes of both mitochondrial respiration and glycolysis become more active. Intensified metabolism might be associated with the increased demand for energy, which is needed to maintain the expression of pluripotency genes and stemness state.

Currently, the number of stem-cell based experimental therapies in neurological injuries and neurodegenerative disorders has been massively increasing. Despite the fact that we still have not obtained strong evidence of mesenchymal stem/stromal cells’ neurogenic effectiveness in vivo, research may need to focus on more appropriate sources that result in more therapeutically promising cell populations. In this study, we used dedifferentiated fat cells (DFAT) that are proven to demonstrate more pluripotent abilities in comparison with standard adipose stromal cells (ASCs). We used the ceiling culture method to establish DFAT cells and to optimize culture conditions with the use of a physioxic environment (5% O2). We also performed neural differentiation tests and assessed the neurogenic and neuroprotective capability of both DFAT cells and ASCs. Our results show that DFAT cells may have a better ability to differentiate into oligodendrocytes, astrocytes, and neuron-like cells, both in culture supplemented with N21 and in co-culture with oxygen–glucose-deprived (OGD) hippocampal organotypic slice culture (OHC) in comparison with ASCs. Results also show that DFAT cells have a different secretory profile than ASCs after contact with injured tissue. In conclusion, DFAT cells constitute a distinct subpopulation and may be an alternative source in cell therapy for the treatment of nervous system disorders.

Rapid developments in stem cell research in recent years have provided a solid foundation for their use in medicine. Over the last few years, hundreds of clinical trials have been initiated in a wide panel of indications. Disorders and injuries of the nervous system still remain a challenge for the regenerative medicine. Neural stem cells (NSCs) are the optimal cells for the central nervous system restoration as they can differentiate into mature cells and, most importantly, functional neurons and glial cells. However, their application is limited by multiple factors such as difficult access to source material, limited cells number, problematic, long and expensive cultivation in vitro, and ethical considerations. On the other hand, according to the available clinical databases, most of the registered clinical trials involving cell therapies were carried out with the use of mesenchymal stem/stromal/signalling cells (MSCs) obtained from afterbirth or adult human somatic tissues. MSCs are the multipotent cells which can also differentiate into neuron-like and glia-like cells under proper conditions in vitro; however, their main therapeutic effect is more associated with secretory and supportive properties. MSCs, as a natural component of cell niche, affect the environment through immunomodulation as well as through the secretion of the trophic factors. In this review, we discuss various therapeutic strategies and activated mechanisms related to bilateral MSC–NSC interactions, differentiation of MSCs towards the neural cells (subpopulation of crest-derived cells) under the environmental conditions, bioscaffolds, or co-culture with NSCs by recreating the conditions of the neural cell niche.

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