Mesenchymal Stromal Cells Nanovesicles Carry microRNA with Nephroprotective Proprieties Regardless of Aging


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Abstract

Containing information molecules from their parent cells and inclining to fuse with targeted cells, bone marrow mesenchymal stromal cells-derived extracellular vesicles (MSCs- EV) are valuable in nanomedicine.

Background:The effects of aging on the paracrine mechanism and in the production and action of MSCs-EV and their cargos of miR-26a and siRNA-26a for the treatment of tubular renal cells under nephrotoxicity injury remain unelucidated.

Objective:The purpose of this study was to evaluate MSCs-EV of different ages and their ability to deliver the cargos of miR-26a and siRNA-26ª to target renal tubular cells affected by nephrotoxicity injury.

Methods:In a model of gentamicin-induced nephrotoxicity, renal tubular cells treated with MSCs-EV expressing or not expressing microRNA-26a were analyzed. Western blotting was utilized to evaluate cell cycle markers, and MTT assay was utilized to evaluate auto-renovation capacity.

Results:Tubular cells under nephrotoxicity injury showed decreased proliferative capacity, but the treatment in the tubular renal cells under nephrotoxicity injury with MSCs-EV expressing microRNA-26a showed nephroprotective effects, regardless of EV age. While the treatment with EV-mediated siRNA-26a failed to preserve the nephroprotective effects equally, regardless of age.

Conclusion:Mesenchymal stromal cell nanovesicles carry microRNA with nephroprotective proprieties regardless of aging.

About the authors

Marcia Convento

Nephrology Division, Department of Medicine, Federal University of Sao Paulo

Author for correspondence.
Email: info@benthamscience.net

Andréia de Oliveira

Nephrology Division, Department of Medicine, Federal University of Sao Paulo

Email: info@benthamscience.net

Mirian Boim

Nephrology Division, Department of Medicine, Federal University of Sao Paulo

Email: info@benthamscience.net

Fernanda Borges

Nephrology Division, Department of Medicine, Federal University of Sao Paulo

Email: info@benthamscience.net

References

  1. Mennan C, Wright K, Bhattacharjee A, Balain B, Richardson J, Roberts S. Isolation and characterisation of mesenchymal stem cells from different regions of the human umbilical cord. BioMed Res Int 2013; 2013: 1-8. doi: 10.1155/2013/916136 PMID: 23984420
  2. Borges FT, Convento MB, Schor N. Bone marrow-derived mesenchymal stromal cell: What next? Stem Cells Cloning 2018; 11: 77-83. doi: 10.2147/SCCAA.S147804 PMID: 30510433
  3. Jones TF, Bekele S, O’Dwyer MJ, Prowle JR. MicroRNAs in acute kidney injury. Nephron J 2018; 140(2): 124-8. doi: 10.1159/000490204 PMID: 29870986
  4. Wang L, Wei J, Da Fonseca Ferreira A, et al. Rejuvenation of senescent endothelial progenitor cells by extracellular vesicles derived from mesenchymal stromal cells. JACC Basic Transl Sci 2020; 5(11): 1127-41. doi: 10.1016/j.jacbts.2020.08.005 PMID: 33294742
  5. Prattichizzo F, Micolucci L, Cricca M, et al. Exosome-based immunomodulation during aging: A nano-perspective on inflammaging. Mech Ageing Dev 2017; 168: 44-53. doi: 10.1016/j.mad.2017.02.008 PMID: 28259747
  6. Takahashi A, Okada R, Nagao K, et al. Publisher Correction: Exosomes maintain cellular homeostasis by excreting harmful DNA from cells. Nat Commun 2018; 9(1): 4109. doi: 10.1038/s41467-018-06613-3 PMID: 30294002
  7. Pernod C, Lamblin A, Cividjian A, Gerome P, Pierre-François W. Use of gentamicin for sepsis and septic shock in anaesthesia-intensive care unit: A clinical practice evaluation. Turk J Anaesthesiol Reanim 2020; 48(5): 399-405. doi: 10.5152/TJAR.2019.57255 PMID: 33103145
  8. Pessoa EA, Convento MB, Silva RG, Oliveira AS, Borges FT, Schor N. Gentamicin-induced preconditioning of proximal tubular LLC-PK1 cells stimulates nitric oxide production but not the synthesis of heat shock protein. Braz J Med Biol Res 2009; 42(7): 614-20. doi: 10.1590/S0100-879X2009005000005 PMID: 19466282
  9. Marques RG, Morales MM, Petroianu A. Brazilian law for scientific use of animals. Acta Cir Bras 2009; 24(1): 69-74. doi: 10.1590/S0102-86502009000100015 PMID: 19169547
  10. Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8(4): 315-7. doi: 10.1080/14653240600855905 PMID: 16923606
  11. Pessoa EA, Convento MB, Castino B, et al. Beneficial effects of isoflavones in the kidney of obese rats are mediated by PPAR-Gamma expression. Nutrients 2020; 12(6): 1624. doi: 10.3390/nu12061624 PMID: 32492810
  12. Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65(1-2): 55-63. doi: 10.1016/0022-1759(83)90303-4 PMID: 6606682
  13. Luiz RS, Rampaso RR, Santos AAC, et al. BM-MSC-derived small extracellular vesicles (sEV) from trained animals presented nephroprotective potential in unilateralureteral obstruction model. J Venom Anim Toxins Incl Trop Dis 2021; 27: e20200187. doi: 10.1590/1678-9199-jvatitd-2020-0187 PMID: 34925478
  14. Lowry O, Rosebrough N, Farr AL, Randall R. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193(1): 265-75. doi: 10.1016/S0021-9258(19)52451-6 PMID: 14907713
  15. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). Method Methods 2001; 25(4): 402-8. doi: 10.1006/meth.2001.1262 PMID: 11846609
  16. Paunesku T, Mittal S, Protić M. et al. Proliferating cell nuclear antigen (PCNA): Ringmaster of the genome. Int J Radiat Biol 2001; 77(10): 1007-21. doi: 10.1080/09553000110069335 PMID: 11682006
  17. Strzalka W, Ziemienowicz A. Proliferating cell nuclear antigen (PCNA): A key factor in DNA replication and cell cycle regulation. Ann Bot 2011; 107(7): 1127-40. doi: 10.1093/aob/mcq243 PMID: 21169293
  18. Théry C, Witwer KW, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the international society for extracellular vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles 2018; 7(1): 1535750. doi: 10.1080/20013078.2018.1535750 PMID: 30637094
  19. Canaud G, Bonventre JV. Cell cycle arrest and the evolution of chronic kidney disease from acute kidney injury. Nephrol Dial Transplant 2015; 30(4): 575-83. doi: 10.1093/ndt/gfu230 PMID: 25016609
  20. Nadasdy T, Laszik Z, Blick KE, Johnson LD, Silva FG. Proliferative activity of intrinsic cell populations in the normal human kidney. J Am Soc Nephrol 1994; 4(12): 2032-9. doi: 10.1681/ASN.V4122032 PMID: 7919156
  21. Witzgall R, Brown D, Schwarz C, Bonventre JV. Localization of proliferating cell nuclear antigen, vimentin, c-Fos, and clusterin in the postischemic kidney. Evidence for a heterogenous genetic response among nephron segments, and a large pool of mitotically active and dedifferentiated cells. J Clin Invest 1994; 93(5): 2175-88. doi: 10.1172/JCI117214 PMID: 7910173
  22. Wu YS, Liang S, Li DY, Wen JH, Tang JX, Liu HF. Cell cycle dysregulation and renal fibrosis. Front Cell Dev Biol 2021; 9: 714320. doi: 10.3389/fcell.2021.714320 PMID: 34900982
  23. Li X, Pan X, Fu X, Yang Y, Chen J, Lin W. MicroRNA-26a: An emerging regulator of renal biology and disease. Kidney Blood Press Res 2019; 44(3): 287-97. doi: 10.1159/000499646 PMID: 31163420
  24. Zhang A, Wang H, Wang B, Yuan Y, Klein JD, Wang XH. Exogenous miR‐26a suppresses muscle wasting and renal fibrosis in obstructive kidney disease. FASEB J 2019; 33(12): 13590-601. doi: 10.1096/fj.201900884R PMID: 31593640
  25. Groot M, Lee H. Sorting mechanisms for MicroRNAs into extracellular vesicles and their associated diseases. Cells 2020; 9(4): 1044. doi: 10.3390/cells9041044 PMID: 32331346
  26. Li R, Hannon GJ, Beach D, Stillman B. Subcellular distribution of p21 and PCNA in normal and repair-deficient cells following DNA damage. Curr Biol 1996; 6(2): 189-99. doi: 10.1016/S0960-9822(02)00452-9 PMID: 8673466
  27. Cayrol C, Knibiehler M, Ducommun B. p21 binding to PCNA causes G1 and G2 cell cycle arrest in p53-deficient cells. Oncogene 1998; 16(3): 311-20. doi: 10.1038/sj.onc.1201543 PMID: 9467956
  28. Koyano T, Namba M, Kobayashi T, et al. The p21 dependent G2 arrest of the cell cycle in epithelial tubular cells links to the early stage of renal fibrosis. Sci Rep 2019; 9(1): 12059. doi: 10.1038/s41598-019-48557-8 PMID: 31427681
  29. Megyesi J, Safirstein RL, Price PM. Induction of p21WAF1/CIP1/SDI1 in kidney tubule cells affects the course of cisplatin-induced acute renal failure. J Clin Invest 1998; 101(4): 777-82. doi: 10.1172/JCI1497 PMID: 9466972
  30. Ju SM, Kim MS, Jo YS, et al. Licorice and its active compound glycyrrhizic acid ameliorates cisplatin-induced nephrotoxicity through inactivation of p53 by scavenging ROS and overexpression of p21 in human renal proximal tubular epithelial cells. Eur Rev Med Pharmacol Sci 2017; 21(4): 890-9. PMID: 28272690
  31. Price PM, Yu F, Kaldis P, et al. Dependence of cisplatin-induced cell death in vitro and in vivo on cyclin-dependent kinase 2. J Am Soc Nephrol 2006; 17(9): 2434-42. doi: 10.1681/ASN.2006020162 PMID: 16914540
  32. Zhu XY, Ebrahimi B, Eirin A, et al. Renal vein levels of MicroRNA-26a are lower in the poststenotic kidney. J Am Soc Nephrol 2015; 26(6): 1378-88. doi: 10.1681/ASN.2014030248 PMID: 25270070
  33. Duan Y, Luo Q, Wang Y, et al. Adipose mesenchymal stem cellderived extracellular vesicles containing microRNA-26a-5p target TLR4 and protect against diabetic nephropathy. J Biol Chem 2020; 295(37): 12868-84. doi: 10.1074/jbc.RA120.012522 PMID: 32580945

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