Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs

By T. Chen, R. C. Lai, M. Lee, A. Choo, C. Lee, S. Lim. Nucleic Acids Research, 2009

625 citations recorded by the source corpus.

Intercellular exchange of protein and RNA-containing microparticles is an increasingly important mode of cell–cell communication. Here we investigate if mesenchymal stem cells (MSCs) known for secreting therapeutic paracrine factors also secrete RNA-containing microparticles. We observed that human embryonic stem cell (hESC)-derived MSC conditioned medium contained small RNAs (less than 300 nt) encapsulated in cholesterol-rich phospholipid vesicles as evidenced by their RNase sensitivity only in the presence of a sodium dodecyl sulfate-based cell lysis buffer, phospholipase A2 and a chelator of cholesterol, cyclodextrin and the restoration of their lower than expected density by detergent or phospholipase A2 treatment. MicroRNAs (miRNAs) such as hsa-let-7b and hsa-let-7g were present in a high precursor (pre)- to mature miRNA ratio by microarray analysis and quantitative reverse transcription–polymerase chain reaction. The pre-miRNAs were cleaved to mature miRNA by RNase III in vitro. High performance liquid chromatography-purified RNA-containing vesicles have a hydrodynamic radius of 55–65 nm and were readily taken up by H9C2 cardiomyocytes. This study suggests that MSCs could facilitate miRNA-mediated intercellular communication by secreting microparticles enriched for pre-miRNA.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c68f31ae4fedc189032eaff20deb88694cdc264f

How researchers see this paper

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In Cancer Research

1. C. Théry
2. Marina Colombo
3. A. Llorente
4. G. Raposo
5. W. Stoorvogel
6. M. Wood
7. S. El Andaloussi
8. Jan Lötvall

In Molecular Biology

1. C. Théry
2. G. Raposo
3. Marina Colombo
4. A. Llorente
5. W. Stoorvogel
6. María Yáñez-Mó
7. Zoraida Andreu
8. M. Wood

Citations in the corpus

• Microvesicles Derived from Adult Human Bone Marrow and Tissue Specific Mesenchymal Stem Cells Shuttle Selected Pattern of miRNAs (2010, background): “However, recent studies [18,44] as well as the present results suggest a selective mechanism of RNA packaging into MVs.”
• Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury. (2013, background): “More specifically, we have also demonstrated that MSC-derived exosomes are taken up by H9C2 cardiomyocytes (Chen et al., 2010).”
• Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. (2010, background): “We also recently demonstrated that the MSC-derived exosomes described here also contained miRNAs and these miRNAs were predominantly in the precursor form (Chen et al., 2010).”
• Exosomes Derived from Mesenchymal Stem Cells (2014, background): “It has been found that miRNAs encapsulated in MSC-derived microparticles are predominantly in their precursor form [51].”
• Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. (2014, background): “A cardiomyocytic cell line captures mesenchymal-derived EVs (Chen et al. 2010).”
• Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy. (2012, background): “Similarly, MSC-derived exosomes were also able to provide protection against myocardial ischaemia (91) and to treat myocardial infarction (92) through the expression of higher levels of precursor forms of hsa-let-7b and hsa-let-7g miRNAs (93).”
• Biological properties of extracellular vesicles and their physiological functions (2015, background): “While cellular mRNA varies in size from 400 to 12,000 nucleotides (nt), RNA detected in EVs has a predominant size of B700 nt (158,159).”
• Circulating microRNAs are new and sensitive biomarkers of myocardial infarction (2010, background): “It has been recently shown that exosomes and microparticles containing miRNAs can be released into the extracellular environment and then be internalized by other cells.(10,11) Therefore, future studies will need to establish whether, following an acute MI, miRNAs in the bloodstream are contained in”
• Review of the Isolation, Characterization, Biological Function, and Multifarious Therapeutic Approaches of Exosomes (2019, background): “Several miRNAs, such as miR210, miR126, miR132, and miR21, loaded in exosomes from mesenchymal stem/stromal cells (MSCs), play significant roles in angiogenesis [135].”
• Exosomes in Cancer Development, Metastasis and Drug Resistance: A Comprehensive Review (2013, positive): “Chen and colleagues have suggested that miRNAs in exosomes secreted by mesenchymal stem cells (MSC) are predominantly pre- and not mature miRNAs [115].”
• Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSC (2011, background): “Furthermore, MSC can secrete micro vesicles which contain certain pre-microRNAs [135].”