Exosomes Shown to Induce Stem Cell Differentiation

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Despite being extensively studied as vehicles controlling cell-to-cell communication, exosomes -small vesicles secreted by all cell types and range in diameter from 30-50 nm – have not yet been reported as being involves in stem cell differentiation.

Last week, a new paper from the lab of Dr. Qiaobing Xu, assistant professor of biomedical engineering at Tufts School of Engineering, described a new paradigm for the role of exosomes in regenerative medicine by describing the utility of exosomes as inducers of differentiation of human stem cells.

In the paper, titled Neuronal Differentiation of Human Mesenchymal Stem Cells Using Exosomes Derived from Differentiating Neuronal Cells, and published in PLoS One, the authors used exosomes from PC12 cells (neuron-like progenitor cells derived from rats) and showed that they could, at various stages of their own differentiation could, in turn, cause bone marrow-derived hMSCs to become neuron-like cells.

The authors used hMSCs at passage 4, which they treated with PC12 exosomes for 1 week, which were growing in DMEM medium with the addition of bFGF.

After 7 days of culture, extracted mRNA expression of neuronal markers was analyzed by qPCR. The results demonstrated that expression of neuronal markers such as miR-221 and 222 was upregulated in the hMSC that successfully differentiated into neuronal lineages.

The table below shows miRNAs enriched in PC12 exosomes and upregulated after NGF treatment as reported in the paper. The hypothesis is that the exosomes acted be delivering miRNA into the stem cells.




While early, the study is the first example describing exosomes as a new paradigm for differentiation of stem cells, thereby setting the stage for further studies into the development of exosomal RNA that might direct differentiation.

At Akron, such differentiation of hMSCs is promoted by our integrated development of growth factors and media – from research to GMP grade – that supports the cells differentiation pathways.



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