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

**Authors:** Yuji S. Takeda, Qiaobing Xu

PMC · DOI: 10.1371/journal.pone.0135111 · 2015-08-06

## 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.

## Key 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.

## Linked entities

- **Genes:** MIR125B (microRNA mir-125b) [NCBI Gene 100314821]

## Full-text entities

- **Genes:** Mir760 (microRNA 760) [NCBI Gene 100314118] {aka rno-mir-760}, Eno2 (enolase 2) [NCBI Gene 24334] {aka NSE, RNEN3}, Ngf (nerve growth factor) [NCBI Gene 310738] {aka Ngfb, beta-NGF}, Mir182 (microRNA 182) [NCBI Gene 100314172] {aka rno-mir-182}, Mir702 (microRNA 702) [NCBI Gene 100526603] {aka rno-mir-702}, Eno2 (enolase 2, gamma neuronal) [NCBI Gene 13807] {aka D6Ertd375e, Eno-2, NSE}, Dnase1 (deoxyribonuclease 1) [NCBI Gene 25633], Mir133b (microRNA 133b) [NCBI Gene 100314078] {aka rno-mir-133b}, Mir1188 (microRNA 1188) [NCBI Gene 100526588] {aka rno-mir-1188}, Fgf2 (fibroblast growth factor 2) [NCBI Gene 54250] {aka Fgf-2, Fgf2a, bFGF}, Mir222 (microRNA 222) [NCBI Gene 100314059] {aka rno-mir-222}, Map2 (microtubule-associated protein 2) [NCBI Gene 25595] {aka MAP2R, Mtap2}, Map2 (microtubule-associated protein 2) [NCBI Gene 17756] {aka G1-397-34, MAP-2, Mtap-2, Mtap2, repro4}, Gapdh (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 24383] {aka BARS-38, Gapd}, MIR125B1 (microRNA 125b-1) [NCBI Gene 406911] {aka MIRN125B1, mir-125b-1}, Mir125b1 (microRNA 125b-1) [NCBI Gene 100314156] {aka Mir125b-1, rno-mir-125b-1}
- **Diseases:** paralysis (MESH:D010243), stroke (MESH:D020521), spinal injury (MESH:D013124), spinal nerve injury (MESH:D061227), tumor (MESH:D009369), sciatic nerve injury (MESH:D020426), peripheral nerve injury (MESH:D059348), traumatic brain injury (MESH:D000070642), glioma (MESH:D005910), melanoma (MESH:D008545), entrapment neuropathy (MESH:D009408), neurodegeneration (MESH:D019636), peripheral nerve (MESH:D010523), Spinal cord injuries (MESH:D013119),  (MESH:D008546)
- **Chemicals:** formalin (MESH:D005557), Bis-Tris (MESH:C026272), DMEM (-), methanol (MESH:D000432), PVDF (MESH:C024865), Triton X-100 (MESH:D017830), Essential Amino Acids (MESH:D000601), SYBR Green I (MESH:C098022), DAPI (MESH:C007293)
- **Species:** Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** B16-F10 — Mus musculus (Mouse), Mouse melanoma, Cancer cell line (CVCL_0159), SH-SY5Y — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0019), PC12 — Rattus norvegicus (Rat), Rat adrenal gland pheochromocytoma, Cancer cell line (CVCL_0481), D9 — Mus musculus (Mouse), Hybridoma (CVCL_C4ST), hMSCs — Homo sapiens (Human), Somatic stem cell (CVCL_WG60)

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC4527703/full.md

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Source: https://tomesphere.com/paper/PMC4527703