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Diabetology & Metabolic Syndrome
Published in: Diabetology & Metabolic Syndrome 1/2018

Open Access 01-12-2018 | Research

The metabolic syndrome modifies the mRNA expression profile of extracellular vesicles derived from porcine mesenchymal stem cells

Authors: Yu Meng, Alfonso Eirin, Xiang-Yang Zhu, Daniel R. O’Brien, Amir Lerman, Andre J. van Wijnen, Lilach O. Lerman

Published in: Diabetology & Metabolic Syndrome | Issue 1/2018

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Abstract

Background

Mesenchymal stem cells (MSCs) perform paracrine functions by releasing extracellular vesicles (EVs) containing microRNA, mRNA, and proteins. We investigated the mRNA content of EVs in metabolic syndrome (MetS) and tested hypothesis that comorbidities interfere with the paracrine functionality of MSCs.

Methods

Mesenchymal stem cells were collected from swine abdominal adipose tissue after 16 weeks of a low- (Lean) or high-calorie (MetS) diet (n = 5 each). We used next-generation mRNAs sequencing to identify mRNAs enriched and depleted in Lean- or MetS-EVs compared to the parent MSCs.

Results

We found 88 and 130 mRNAs enriched in Lean-EVs and MetS-EVs, respectively, of which only eight were common genes encoding proteins related to the nucleus, endoplasmic reticulum, and membrane fraction. Lean-EVs were enriched with mRNAs primarily involved in transcription regulation and the transforming growth factor (TGF)-β signaling pathway, but devoid of genes related to regulation of inflammation. In contrast, MetS-EVs contained mRNAs involved in translational regulation and modulation of inflammation mediated by chemokines and cytokines, but lacked mRNAs related to TGF-β signaling. mRNAs enriched in EVs have the potential to target a significant proportion of genes enriched in EVs, but only 4% microRNA target genes overlap between Lean- and MetS-EVs. Co-culture with MetS-EVs also increased renal tubular cell inflammation in-vitro.

Conclusions

Metabolic syndrome may affect immunomodulatory function of porcine MSCs by modifying mRNA profiles of the EVs that they produce and post-transcriptional regulation. These observations may have important implications for cell-based therapy, and support development of strategies to improve the efficacy of MSCs and their EVs.
Appendix
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Literature
1.
Dominici M, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315–7.CrossRefPubMed
2.
Majka M, et al. Concise review: mesenchymal stem cells in cardiovascular regeneration: emerging research directions and clinical applications. Stem Cells Transl Med. 2017;6(10):1859–67.CrossRefPubMed
3.
Alagesan S, Griffin MD. Autologous and allogeneic mesenchymal stem cells in organ transplantation: what do we know about their safety and efficacy? Curr Opin Organ Transplant. 2014;19(1):65–72.CrossRefPubMed
4.
5.
Nargesi AA, Lerman LO, Eirin A. Mesenchymal stem cell-derived extracellular vesicles for kidney repair: current status and looming challenges. Stem Cell Res Ther. 2017;8(1):273.CrossRef
6.
7.
8.
Eirin A, et al. MicroRNA and mRNA cargo of extracellular vesicles from porcine adipose tissue-derived mesenchymal stem cells. Gene. 2014;551(1):55–64.CrossRefPubMedPubMedCentral
9.
Eirin A, et al. Glomerular hyperfiltration in obese African American hypertensive patients is associated with elevated urinary mitochondrial-DNA copy number. Am J Hypertens. 2017;30:1112–9.CrossRefPubMed
10.
Eirin A, et al. Comparative proteomic analysis of extracellular vesicles isolated from porcine adipose tissue-derived mesenchymal stem/stromal cells. Sci Rep. 2016;6:36120.CrossRefPubMedPubMedCentral
11.
Kornicka K, Houston J, Marycz K. Dysfunction of mesenchymal stem cells isolated from metabolic syndrome and type 2 diabetic patients as result of oxidative stress and autophagy may limit their potential therapeutic use. Stem Cell Rev. 2018;14(3):337–45.CrossRefPubMedPubMedCentral
12.
Marycz K, et al. Equine metabolic syndrome affects viability, senescence, and stress factors of equine adipose-derived mesenchymal stromal stem cells: new insight into EqASCs isolated from EMS horses in the context of their aging. Oxid Med Cell Longev. 2016;2016:4710326.PubMed
13.
Meng Y, et al. Obesity-induced mitochondrial dysfunction in porcine adipose tissue-derived mesenchymal stem cells. J Cell Physiol. 2018;233(8):5926–36.CrossRefPubMed
14.
Pawar AS, et al. Adipose tissue remodeling in a novel domestic porcine model of diet-induced obesity. Obesity (Silver Spring). 2015;23(2):399–407.CrossRef
15.
16.
Eirin A, et al. Adipose tissue-derived mesenchymal stem cells improve revascularization outcomes to restore renal function in swine atherosclerotic renal artery stenosis. Stem Cells. 2012;30(5):1030–41.CrossRefPubMedPubMedCentral
17.
Eirin A, et al. Renal vein cytokine release as an index of renal parenchymal inflammation in chronic experimental renal artery stenosis. Nephrol Dial Transplant. 2014;29(2):274–82.CrossRefPubMed
18.
Meng Y, et al. The metabolic syndrome alters the miRNA signature of porcine adipose tissue-derived mesenchymal stem cells. Cytometry Part A. 2017;93:93–103.CrossRef
19.
20.
Eirin A, et al. Integrated transcriptomic and proteomic analysis of the molecular cargo of extracellular vesicles derived from porcine adipose tissue-derived mesenchymal stem cells. PLoS ONE. 2017;12(3):e0174303.CrossRefPubMedPubMedCentral
21.
22.
Kalari KR, et al. MAP-RSeq: mayo analysis pipeline for RNA sequencing. BMC Bioinform. 2014;15:224.CrossRef
23.
Robinson MD, McCarthy DJ, Smyth GK. edgeR: a bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010;26(1):139–40.CrossRefPubMed
24.
Dudakovic A, et al. High-resolution molecular validation of self-renewal and spontaneous differentiation in clinical-grade adipose-tissue derived human mesenchymal stem cells. J Cell Biochem. 2014;115(10):1816–28.CrossRefPubMedPubMedCentral
25.
Conley SM, et al. Metabolic syndrome alters expression of insulin signaling-related genes in swine mesenchymal stem cells. Gene. 2018;644:101–6.CrossRefPubMed
26.
Meng Y, et al. The metabolic syndrome alters the miRNA signature of porcine adipose tissue-derived mesenchymal stem cells. Cytometry Part A. 2018;93(1):93–103.CrossRef
27.
Martinez FO, et al. Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol. 2006;177(10):7303–11.CrossRefPubMed
28.
Zhu XY, et al. Mesenchymal stem cells and endothelial progenitor cells decrease renal injury in experimental swine renal artery stenosis through different mechanisms. Stem Cells. 2013;31(1):117–25.CrossRefPubMedPubMedCentral
29.
Barbagallo I, et al. Diabetic human adipose tissue-derived mesenchymal stem cells fail to differentiate in functional adipocytes. Exp Biol Med (Maywood). 2017;242(10):1079–85.CrossRef
30.
Saleh F, et al. Adipose-derived mesenchymal stem cells in the treatment of obesity: a systematic review of longitudinal studies on preclinical evidence. Curr Stem Cell Res Ther. 2018;13(6):466–75.CrossRefPubMed
31.
Andaloussi SELA, et al. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov. 2013;12(5):347–57.CrossRef
32.
Shim EK, et al. Autogenous mesenchymal stem cells from the vertebral body enhance intervertebral disc regeneration by paracrine interaction: an in vitro pilot study. Cell Transplant. 2016;25:1819–32.CrossRefPubMed
33.
Otabe K, et al. Transcription factor Mohawk controls tenogenic differentiation of bone marrow mesenchymal stem cells in vitro and in vivo. J Orthop Res. 2015;33(1):1–8.CrossRefPubMed
34.
Kokabu S, et al. BMP3 suppresses osteoblast differentiation of bone marrow stromal cells via interaction with Acvr2b. Mol Endocrinol. 2012;26(1):87–94.CrossRefPubMed
35.
Rao C, et al. Crosstalk between canonical TGF-beta/Smad and Wnt/beta-catenin signaling pathway. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2013;42(5):591–6.PubMed
36.
Li C, et al. Apc deficiency alters pulmonary epithelial cell fate and inhibits Nkx2.1 via triggering TGF-beta signaling. Dev Biol. 2013;378(1):13–24.CrossRefPubMed
37.
Wang Y, et al. Predictive role of multilocus genetic polymorphisms in cardiovascular disease and inflammation-related genes on chronic kidney disease in Type 2 diabetes—an 8-year prospective cohort analysis of 1163 patients. Nephrol Dial Transplant. 2012;27(1):190–6.CrossRefPubMed
38.
Luk AO, et al. Predictive role of polymorphisms in interleukin-5 receptor alpha-subunit, lipoprotein lipase, integrin A2 and nitric oxide synthase genes on ischemic stroke in type 2 diabetes—an 8-year prospective cohort analysis of 1327 Chinese patients. Atherosclerosis. 2011;215(1):130–5.CrossRefPubMed
39.
Yurdagul A Jr, et al. alpha5beta1 integrin signaling mediates oxidized low-density lipoprotein-induced inflammation and early atherosclerosis. Arterioscler Thromb Vasc Biol. 2014;34(7):1362–73.CrossRefPubMedPubMedCentral
40.
Peters MA, et al. The loss of alpha2beta1 integrin suppresses joint inflammation and cartilage destruction in mouse models of rheumatoid arthritis. Arthritis Rheum. 2012;64(5):1359–68.CrossRefPubMed
41.
Huang JB, et al. Inhibition of the PI3K/AKT pathway reduces tumor necrosis factor-alpha production in the cellular response to wear particles in vitro. Artif Organs. 2013;37(3):298–307.CrossRefPubMed
42.
Wang J, Maldonado MA. The ubiquitin-proteasome system and its role in inflammatory and autoimmune diseases. Cell Mol Immunol. 2006;3(4):255–61.PubMed
43.
Zhou H, et al. High EGFR_1 inside-out activated inflammation-induced motility through SLC2A1-CCNB2-HMMR-KIF11-NUSAP1-PRC1-UBE2C. J Cancer. 2015;6(6):519–24.CrossRefPubMedPubMedCentral
44.
Mazumdar T, et al. Regulation of NF-kappaB activity and inducible nitric oxide synthase by regulatory particle non-ATPase subunit 13 (Rpn13). Proc Natl Acad Sci USA. 2010;107(31):13854–9.CrossRefPubMed
45.
46.
47.
Filipczak PT, et al. HSPA2 overexpression protects V79 fibroblasts against bortezomib-induced apoptosis. Biochem Cell Biol. 2012;90(2):224–31.CrossRefPubMed
48.
Walther N, et al. Differentiation-specific action of orphan nuclear receptor NR5A1 (SF-1): transcriptional regulation in luteinizing bovine theca cells. Reprod Biol Endocrinol. 2006;4:64.CrossRefPubMedPubMedCentral
49.
Der-Boghossian AH, et al. Role of insulin on jejunal PepT1 expression and function regulation in diabetic male and female rats. Can J Physiol Pharmacol. 2010;88(7):753–9.CrossRefPubMed
50.
51.
Noer A, et al. Stable CpG hypomethylation of adipogenic promoters in freshly isolated, cultured, and differentiated mesenchymal stem cells from adipose tissue. Mol Biol Cell. 2006;17(8):3543–56.CrossRefPubMedPubMedCentral
Metadata
Title
The metabolic syndrome modifies the mRNA expression profile of extracellular vesicles derived from porcine mesenchymal stem cells
Authors
Yu Meng
Alfonso Eirin
Xiang-Yang Zhu
Daniel R. O’Brien
Amir Lerman
Andre J. van Wijnen
Lilach O. Lerman
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Diabetology & Metabolic Syndrome / Issue 1/2018
Electronic ISSN: 1758-5996
DOI
https://doi.org/10.1186/s13098-018-0359-9

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