Abstract
Potential mechanisms involved in neural differentiation of adipocyte derived stem cells (ADSCs) are still unclear. In the present study, extracellular vesicles (EVs) were tested as a potential mechanism involved in the neuronal differentiation of stem cells. In order to address this, ADSCs and neurons (BRC) were established in primary culture and co-culture at three timepoints. Furthermore, we evaluated protein and transcript levels of differentiated ADSCs from the same timepoints, to confirm phenotype change to neuronal linage. Importantly, neuron-derived EVs cargo and EVs originated from co-culture were analyzed and tested in terms of function, such as gene expression and microRNA levels related to the adult neurogenesis process. Ideal neuron-like cells were identified and, therefore, we speculated the in vivo function of these cells in acute sciatic nerve injury. Overall, our data demonstrated that ADSCs in indirect contact with neurons differentiated into neuron-like cells. Neuron-derived EVs appear to play an important role in this process carrying SNAP25, miR-132 and miR-9. Additionally, in vivo neuron-like cells helped in microenvironment modulation probably preventing peripheral nerve injury degeneration. Consequently, our findings provide new insight of future methods of ADSC induction into neuronal linage to be applied in peripheral nerve (PN) injury.
Highlights
Interactions between cells can be studied through cell communication mediated by extracellular vesicles (EVs)[1]
In order to do so we looked at the cellular communication by small EVs4,25,26, measuring transcript levels of mRNA and microRNAs related with adult neurogenesis[27], in co-cultured differentiated Adipose-derived stem cells (ADSCs) induced by neurons, and in differentiated ADSCs induced only by neuron-derived EVs, to find the most neuron-like cells, which could be used in the in vivo study
We were not able to detect Snap[25] in ADSC-CCs on D3; we detected some transcripts on D7 and D14 (Fig. 1d)
Summary
Interactions between cells can be studied through cell communication mediated by extracellular vesicles (EVs)[1]. These exchanges can persuade physical and phenotypical changes, for example, inducing recipient cells to differentiate into additional cell types[2,3], being extremely useful for cellular therapies applied in nerve injury regeneration[4]. Www.nature.com/scientificreports epigenetic modifications[11,12], playing a key role in intercellular communication, proving useful in regenerative stem cell therapies[11,13,14,15]. ADSCs can be modulated by other cells to start its differentiation process[18] and can be an alternative cellular therapy to be used in nerve regeneration and microenvironment modulation after nerve injury[18,19,20,21]
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