MiR-133b promotes neural plasticity and functional recovery after treatment of stroke with multipotent mesenchymal stromal cells in rats via transfer of exosome-enriched extracellular particles

By Hongqi Xin, Yi Li, Zhongwu Liu, Xinli Wang, Xia Shang, Yisheng Cui, Z. Zhang, Michael Chopp. Stem Cells, 2013

687 citations recorded by the source corpus.

To test, in vivo, the hypothesis that exosomes from multipotent mesenchymal stromal cells (MSCs) mediate microRNA 133b (miR‐133b) transfer which promotes neurological recovery from stroke, we used knockin and knockdown technologies to upregulate or downregulate the miR‐133b level in MSCs (miR‐133b+MSCs or miR‐133b−MSCs) and their corresponding exosomes, respectively. Rats were subjected to middle cerebral artery occlusion (MCAo) and were treated with naïve MSCs, miR‐133b+MSCs, or miR‐133b−MSC at 1 day after MCAo. Compared with controls, rats receiving naïve MSC treatment significantly improved functional recovery and exhibited increased axonal plasticity and neurite remodeling in the ischemic boundary zone (IBZ) at day 14 after MCAo. The outcomes were significantly enhanced with miR‐133b+MSC treatment, and were significantly decreased with miR‐133b−MSC treatment, compared to naïve MSC treatment. The miR‐133b level in exosomes collected from the cerebral spinal fluid was significantly increased after miR‐133b+MSC treatment, and was significantly decreased after miR‐133b−MSC treatment at day 14 after MCAo, compared to naïve MSC treatment. Tagging exosomes with green fluorescent protein demonstrated that exosomes‐enriched extracellular particles were released from MSCs and transferred to adjacent astrocytes and neurons. The expression of selective targets for miR‐133b, connective tissue growth factor and ras homolog gene family member A, was significantly decreased in the IBZ after miR‐133b+MSC treatment, while their expression remained at similar elevated levels after miR‐133b−MSC treatment, compared to naïve MSC treatment. Collectively, our data suggest that exosomes from MSCs mediate the miR‐133b transfer to astrocytes and neurons, which regulate gene expression, subsequently benefit neurite remodeling and functional recovery after stroke. STEM Cells 2013;31:2737–2746

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3938b85a292b85401e19dcee05c257cbbba9839b

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. C. Théry
2. A. Llorente
3. W. Stoorvogel
4. P. Vader
5. Jan Lötvall
6. Edit I. Buzás
7. María Yáñez-Mó
8. Ramesh C. Gupta

In Molecular Biology

1. C. Théry
2. A. Llorente
3. W. Stoorvogel
4. María Yáñez-Mó
5. Zoraida Andreu
6. P. Vader
7. Jan Lötvall
8. Edit I. Buzás

Citations in the corpus

• Mesenchymal stem cell-derived extracellular vesicles: novel frontiers in regenerative medicine (2018, background): “They also demonstrated that MSC-EVs through transfer of miR-133b to neuron cells and astrocytes enhanced neurite remodeling and improved functional recovery in the rat stroke model [57].”
• Applying extracellular vesicles based therapeutics in clinical trials – an ISEV position paper (2015, background): “ery following ischaemic stroke in a rat model (204) and miR-22 for the MSC-EV mediated anti-apoptotic effects”
• Biological properties of extracellular vesicles and their physiological functions (2015, background): “EVs that enter the CNS from the periphery may also exhibit regenerative functions: MSC-EVs were shown to transfer neuroregenerative miRNAs to astrocytes and neurons in a rat model of stroke (596).”
• Mechanisms of mesenchymal stem/stromal cell function (2016, background): “and recovery by virtue of transfer of miR-133b [170, 171].”