Neuronal Differentiation of Human Mesenchymal Stem Cells Using Exosomes Derived from Differentiating Neuronal Cells

TL;DR

This study shows that exosomes from neuronal cells can help human stem cells turn into neuron-like cells by delivering specific microRNAs.

Contribution

The study demonstrates that miR-125b in neuronal exosomes promotes stem cell neuronal differentiation.

Findings

MSCs treated with PC12-derived exosomes showed neuron-like morphology and upregulated neuronal markers.

miR-125b was significantly more abundant in PC12-derived exosomes compared to melanoma-derived exosomes.

Exosome-delivered miRNAs may be a key mechanism for inducing neuronal differentiation in stem cells.

Abstract

Exosomes deliver functional proteins and genetic materials to neighboring cells, and have potential applications for tissue regeneration. One possible mechanism of exosome-promoted tissue regeneration is through the delivery of microRNA (miRNA). In this study, we hypothesized that exosomes derived from neuronal progenitor cells contain miRNAs that promote neuronal differentiation. We treated mesenchymal stem cells (MSCs) daily with exosomes derived from PC12 cells, a neuronal cell line, for 1 week. After the treatment with PC12-derived exosomes, MSCs developed neuron-like morphology, and gene and protein expressions of neuronal markers were upregulated. Microarray analysis showed that the expression of miR-125b, which is known to play a role in neuronal differentiation of stem cells, was much higher in PC12-derived exosomes than in exosomes from B16-F10 melanoma cells. These results suggest that the delivery of miRNAs contained in PC12-derived exosomes is a possible mechanism explaining the neuronal differentiation of MSC.

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