nach oben

Journal of Cardiovascular Translational Research

Erschienen in:

01.10.2018 | Original Article

Transplantation of Cardiac Mesenchymal Stem Cell-Derived Exosomes for Angiogenesis

verfasst von: Chengwei Ju, Youngjun Li, Yan Shen, Yutao Liu, Jingwen Cai, Naifeng Liu, Gengshan Ma, Yaoliang Tang

Erschienen in: Journal of Cardiovascular Translational Research | Ausgabe 5/2018

Einloggen, um Zugang zu erhalten

Abstract

We demonstrated the effects of exosomes secreted by cardiac mesenchymal stem cells (C-MSC-Exo) in protecting acute ischemic myocardium from reperfusion injury. To investigate the effect of exosomes from C-MSC on angiogenesis, we injected C-MSC-Exo or PBS intramuscularly into ischemic hind limb. Blood perfusion of limb was evaluated by laser Doppler Imaging. We observed that ischemic limb treated with C-MSC-Exo exhibits improved blood perfusion compared to ischemic limb treated with PBS at 2 weeks and 1 month after induction of limb ischemia. To explore the potential mechanisms underlying C-MSC-Exo’s angiogenetic effect, we performed microRNA array analysis and identify mmu-miR-7116-5p as the most abundant enriched miRNA detected in C-MSC-Exo. Bioinformatics’ analysis shows that miR-7116-5p negatively regulates protein polyubiquitination. In conclusion, our study demonstrated that intramuscular delivery of C-MSC-Exo after limb ischemia improves blood perfusion, and we identified the most abundant miRNAs that are preferentially enriched in C-MSC-Exo.

Gaziano, T. A., Bitton, A., Anand, S., Abrahams-Gessel, S., & Murphy, A. (2010). Growing epidemic of coronary heart disease in low- and middle-income countries. Current Problems in Cardiology, 35, 72–115. https://doi.org/10.1016/j.cpcardiol.2009.10.002.CrossRefPubMedPubMedCentral

Xin, M., Olson, E. N., & Bassel-Duby, R. (2013). Mending broken hearts: cardiac development as a basis for adult heart regeneration and repair. Nature Reviews. Molecular Cell Biology, 14, 529–541. https://doi.org/10.1038/nrm3619.CrossRefPubMedPubMedCentral

Steinhauser, M. L., & Lee, R. T. (2011). Regeneration of the heart. EMBO Mol Med, 3, 701–712. https://doi.org/10.1002/emmm.201100175.CrossRefPubMedPubMedCentral

Domenech, M., Polo-Corrales, L., Ramirez-Vick, J. E., & Freytes, D. O. (2016). Tissue Engineering Strategies for Myocardial Regeneration: Acellular Versus Cellular Scaffolds? Tissue Engineering. Part B, Reviews, 22, 438–458. https://doi.org/10.1089/ten.TEB.2015.0523.CrossRefPubMedPubMedCentral

Wang, Z., et al. (2018). Regenerative Therapy for Cardiomyopathies. Journal of Cardiovascular Translational Research. https://doi.org/10.1007/s12265-018-9807-z.

Foussas, S. G., & Tsiaousis, G. Z. (2008). Revascularization treatment in patients with coronary artery disease. Hippokratia, 12, 3–10.PubMedPubMedCentral

Loffler, A. I., & Bourque, J. M. (2016). Coronary Microvascular Dysfunction, Microvascular Angina, and Management. Current Cardiology Reports, 18, 1. https://doi.org/10.1007/s11886-015-0682-9.CrossRefPubMedPubMedCentral

Awada, H. K., Hwang, M. P., & Wang, Y. (2016). Towards comprehensive cardiac repair and regeneration after myocardial infarction: Aspects to consider and proteins to deliver. Biomaterials, 82, 94–112. https://doi.org/10.1016/j.biomaterials.2015.12.025.CrossRefPubMed

Djohan, A. H., Sia, C. H., Lee, P. S., & Poh, K. K. (2018). Endothelial Progenitor Cells in Heart Failure: an Authentic Expectation for Potential Future Use and a Lack of Universal Definition. Journal of Cardiovascular Translational Research. https://doi.org/10.1007/s12265-018-9810-4.

10.

Tang, Y. L., et al. (2013). Cardiac-derived stem cell-based therapy for heart failure: progress and clinical applications. Experimental Biology and Medicine (Maywood, N.J.), 238, 294–300. https://doi.org/10.1177/1535370213477982.CrossRef

11.

Ruan, X. F., et al. (2018). Exosomes from Suxiao Jiuxin pill-treated cardiac mesenchymal stem cells decrease H3K27 demethylase UTX expression in mouse cardiomyocytes in vitro. Acta Pharmacologica Sinica, 39, 579–586. https://doi.org/10.1038/aps.2018.18.CrossRefPubMedPubMedCentral

12.

Ruan, X. F., et al. (2018). Suxiao Jiuxin pill promotes exosome secretion from mouse cardiac mesenchymal stem cells in vitro. Acta Pharmacologica Sinica, 39, 569–578. https://doi.org/10.1038/aps.2018.19.CrossRefPubMedPubMedCentral

13.

Chen, L., et al. (2012). The role of notch 1 activation in cardiosphere derived cell differentiation. Stem Cells and Development, 21, 2122–2129. https://doi.org/10.1089/scd.2011.0463.CrossRefPubMedPubMedCentral

14.

Chen, L., et al. (2014). Infrared fluorescent protein 1.4 genetic labeling tracks engrafted cardiac progenitor cells in mouse ischemic hearts. PloS One, 9, e107841. https://doi.org/10.1371/journal.pone.0107841.CrossRefPubMedPubMedCentral

15.

Klimczak, A., & Kozlowska, U. (2016). Mesenchymal Stromal Cells and Tissue-Specific Progenitor Cells: Their Role in Tissue Homeostasis. Stem Cells International, 2016, 4285215. https://doi.org/10.1155/2016/4285215.CrossRefPubMed

16.

Tang, Y. L., et al. (2004). Autologous mesenchymal stem cell transplantation induce VEGF and neovascularization in ischemic myocardium. Regulatory Peptides, 117, 3–10.CrossRefPubMed

17.

Tang, Y. L., et al. (2005). Paracrine action enhances the effects of autologous mesenchymal stem cell transplantation on vascular regeneration in rat model of myocardial infarction. Ann Thorac Surg, 80, 229–236; discussion 236-227. https://doi.org/10.1016/j.athoracsur.2005.02.072.CrossRefPubMed

18.

Zhang, L., et al. (2014). Inhibition of stearoyl-coA desaturase selectively eliminates tumorigenic Nanog-positive cells: improving the safety of iPS cell transplantation to myocardium. Cell Cycle, 13, 762–771. https://doi.org/10.4161/cc.27677.CrossRefPubMedPubMedCentral

19.

Chen, L., et al. (2013). Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury. Biochemical and Biophysical Research Communications, 431, 566–571. https://doi.org/10.1016/j.bbrc.2013.01.015.CrossRefPubMedPubMedCentral

20.

Li, P., et al. (2018). Serum Exosomes Attenuate H2O2-Induced Apoptosis in Rat H9C2 Cardiomyocytes via ERK1/2. Journal of Cardiovascular Translational Research. https://doi.org/10.1007/s12265-018-9791-3.

21.

Sahoo, S., et al. (2011). Exosomes from human CD34(+) stem cells mediate their proangiogenic paracrine activity. Circ Res, 109, 724–728. https://doi.org/10.1161/CIRCRESAHA.111.253286.CrossRefPubMedPubMedCentral

22.

Khan, M., et al. (2015). Embryonic stem cell-derived exosomes promote endogenous repair mechanisms and enhance cardiac function following myocardial infarction. Circulation Research, 117, 52–64. https://doi.org/10.1161/CIRCRESAHA.117.305990.CrossRefPubMedPubMedCentral

23.

Kishore, R., & Khan, M. (2016). More Than Tiny Sacks: Stem Cell Exosomes as Cell-Free Modality for Cardiac Repair. Circulation Research, 118, 330–343. https://doi.org/10.1161/CIRCRESAHA.115.307654.CrossRefPubMedPubMedCentral

24.

Kishore, R., & Khan, M. (2017). Cardiac cell-derived exosomes: changing face of regenerative biology. European Heart Journal, 38, 212–215. https://doi.org/10.1093/eurheartj/ehw324.CrossRefPubMed

25.

Lu, M., et al. (2018). The Exosome-Derived Biomarker in Atherosclerosis and Its Clinical Application. Journal of Cardiovascular Translational Research. https://doi.org/10.1007/s12265-018-9796-y.

26.

Chen, L., et al. (2013). Two-step protocol for isolation and culture of cardiospheres. Methods in molecular biology (Clifton, N.J.), 1036, 75–80. https://doi.org/10.1007/978-1-62703-511-8_6.CrossRef

27.

Tang, Y. L., et al. (2009). Hypoxic preconditioning enhances the benefit of cardiac progenitor cell therapy for treatment of myocardial infarction by inducing CXCR4 expression. Circulation Research, 104, 1209–1216. https://doi.org/10.1161/CIRCRESAHA.109.197723.CrossRefPubMedPubMedCentral

28.

Wang, Y., et al. (2015). Exosomes/microvesicles from induced pluripotent stem cells deliver cardioprotective miRNAs and prevent cardiomyocyte apoptosis in the ischemic myocardium. International Journal of Cardiology, 192, 61–69. https://doi.org/10.1016/j.ijcard.2015.05.020.CrossRefPubMed

29.

Chen, Z., et al. (2017). Isolation of Extracellular Vesicles from Stem Cells. Methods in Molecular Biology (Clifton, N.J.), 1660, 389–394. https://doi.org/10.1007/978-1-4939-7253-1_32.CrossRef

30.

Helwa, I., et al. (2017). A Comparative Study of Serum Exosome Isolation Using Differential Ultracentrifugation and Three Commercial Reagents. PloS One, 12, e0170628. https://doi.org/10.1371/journal.pone.0170628.CrossRefPubMedPubMedCentral

31.

Zhang, J., et al. (2015). Exosome and exosomal microRNA: trafficking, sorting, and function. Genomics Proteomics Bioinformatics, 13, 17–24. https://doi.org/10.1016/j.gpb.2015.02.001.CrossRefPubMedPubMedCentral

32.

Pathan, M., et al. (2017). A novel community driven software for functional enrichment analysis of extracellular vesicles data. Journal of Extracellular Vesicles, 6, 1321455. https://doi.org/10.1080/20013078.2017.1321455.CrossRefPubMedPubMedCentral

33.

He, Q., Wang, Q., Yuan, C., & Wang, Y. (2017). Downregulation of miR-7116-5p in microglia by MPP(+) sensitizes TNF-alpha production to induce dopaminergic neuron damage. Glia, 65, 1251–1263. https://doi.org/10.1002/glia.23153.CrossRefPubMed

34.

Ni, J., Sun, Y., & Liu, Z. (2018). The Potential of Stem Cells and Stem Cell-Derived Exosomes in Treating Cardiovascular Diseases. Journal of Cardiovascular Translational Research. https://doi.org/10.1007/s12265-018-9799-8.

35.

Campbell, C. R., Berman, A. E., Weintraub, N. L., & Tang, Y. L. (2016). Electrical stimulation to optimize cardioprotective exosomes from cardiac stem cells. Medical Hypotheses, 88, 6–9. https://doi.org/10.1016/j.mehy.2015.12.022.CrossRefPubMedPubMedCentral

36.

Pigati, L., et al. (2010). Selective release of microRNA species from normal and malignant mammary epithelial cells. PloS One, 5, e13515. https://doi.org/10.1371/journal.pone.0013515.CrossRefPubMedPubMedCentral

37.

Villarroya-Beltri, C., et al. (2013). Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nature Communications, 4, 2980. https://doi.org/10.1038/ncomms3980.CrossRefPubMed

38.

Santangelo, L., et al. (2016). The RNA-Binding Protein SYNCRIP Is a Component of the Hepatocyte Exosomal Machinery Controlling MicroRNA Sorting. Cell Reports, 17, 799–808. https://doi.org/10.1016/j.celrep.2016.09.031.CrossRefPubMed

39.

Liu, X., Yuan, W., Yang, L., Li, J., & Cai, J. (2018). miRNA Profiling of Exosomes from Spontaneous Hypertensive Rats Using Next-Generation Sequencing. Journal of Cardiovascular Translational Research. https://doi.org/10.1007/s12265-017-9784-7.

Titel: Transplantation of Cardiac Mesenchymal Stem Cell-Derived Exosomes for Angiogenesis
verfasst von: Chengwei Ju
Youngjun Li
Yan Shen
Yutao Liu
Jingwen Cai
Naifeng Liu
Gengshan Ma
Yaoliang Tang
Publikationsdatum: 01.10.2018
Verlag: Springer US
Erschienen in: Journal of Cardiovascular Translational Research / Ausgabe 5/2018
Print ISSN: 1937-5387
Elektronische ISSN: 1937-5395
DOI: https://doi.org/10.1007/s12265-018-9824-y

Neu im Fachgebiet Kardiologie

Screening-Mammografie offenbart erhöhtes Herz-Kreislauf-Risiko

26.04.2024 Mammografie Nachrichten

Routinemäßige Mammografien helfen, Brustkrebs frühzeitig zu erkennen. Anhand der Röntgenuntersuchung lassen sich aber auch kardiovaskuläre Risikopatientinnen identifizieren. Als zuverlässiger Anhaltspunkt gilt die Verkalkung der Brustarterien.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Adipositas-Medikament auch gegen Schlafapnoe wirksam

24.04.2024 Adipositas Nachrichten

Der als Antidiabetikum sowie zum Gewichtsmanagement zugelassene Wirkstoff Tirzepatid hat in Studien bei adipösen Patienten auch schlafbezogene Atmungsstörungen deutlich reduziert, informiert der Hersteller in einer Vorab-Meldung zum Studienausgang.

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 5/2018

The Application of Induced Pluripotent Stem Cells in Cardiac Disease Modeling and Drug Testing

Regenerative Therapy for Cardiomyopathies

Exosome-Derived Dystrophin from Allograft Myogenic Progenitors Improves Cardiac Function in Duchenne Muscular Dystrophic Mice

Stem Cell Homing: a Potential Therapeutic Strategy Unproven for Treatment of Myocardial Injury