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Cells2019; 8(2); 80; doi: 10.3390/cells8020080

Metformin Increases Proliferative Activity and Viability of Multipotent Stromal Stem Cells Isolated from Adipose Tissue Derived from Horses with Equine Metabolic Syndrome.

Abstract: In this study, we investigated the influence of metformin (MF) on proliferation and viability of adipose-derived stromal cells isolated from horses (EqASCs). We determined the effect of metformin on cell metabolism in terms of mitochondrial metabolism and oxidative status. Our purpose was to evaluate the metformin effect on cells derived from healthy horses (EqASC) and individuals affected by equine metabolic syndrome (EqASC). The cells were treated with 0.5 μM MF for 72 h. The proliferative activity was evaluated based on the measurement of BrdU incorporation during DNA synthesis, as well as population doubling time rate (PDT) and distribution of EqASCs in the cell cycle. The influence of metformin on EqASC viability was determined in relation to apoptosis profile, mitochondrial membrane potential, oxidative stress markers and / mRNA ratio. Further, we were interested in possibility of metformin affecting the Wnt3a signalling pathway and, thus, we determined mRNA and protein level of and β-catenin. Finally, using a two-tailed RT-qPCR method, we investigated the expression of , , , and . Obtained results indicate pro-proliferative and anti-apoptotic effects of metformin on EqASCs. In this study, MF significantly improved proliferation of EqASCs, which manifested in increased synthesis of DNA and lowered PDT value. Additionally, metformin improved metabolism and viability of cells, which correlated with higher mitochondrial membrane potential, reduced apoptosis and increased /β-catenin expression. Metformin modulates the miRNA expression differently in EqASC and EqASC. Metformin may be used as a preconditioning agent which stimulates proliferative activity and viability of EqASCs.
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Publication Date: 2019-01-22 PubMed ID: 30678275PubMed Central: PMC6406832DOI: 10.3390/cells8020080Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The article describes a study that investigated how the use of metformin influenced the growth and survival of certain stem cells derived from horse fat tissue. This research specifically looked at cells from healthy horses and those suffering from equine metabolic syndrome.

Objective of Research

  • The researchers aimed to understand the impact of the drug metformin on the proliferation (growth and reproduction) and viability (ability to survive or live successfully) of adipose-derived stromal cells isolated from horses, specifically referring to EqASCs which are derived from equine adipose tissue.

Methodology

  • The cells were treated with metformin for 72 hours, followed by evaluating their proliferative activity based on DNA synthesis and population doubling time rate (the time it takes for the cell population to double).
  • The researchers also studied the distribution of EqASCs in the cell cycle and their viability in relation to the apoptosis profile, mitochondrial membrane potential (an indicator of cell health), oxidative stress markers (measures of cell damage), and mRNA ratio (mRNA helps in protein synthesis within the cell).
  • Further, the impact of metformin on the Wnt3a signalling pathway was examined by determining mRNA and protein level.
  • The expression of multiple proteins was also investigated using a two-tailed RT-qPCR method.

Findings

  • The results showed that metformin had pro-proliferative and anti-apoptotic effects on EqASCs, meaning it enhanced cell growth and survival.
  • Metformin significantly improved the proliferation of EqASCs, as shown by an increase in DNA synthesis and a decrease in population doubling time.
  • The drug also improved cell metabolism and viability, corroborated by the increased mitochondrial membrane potential, reduced apoptosis, and increased expression in certain protein markers.
  • The study found that metformin modulates the expression of certain proteins differently in healthy and metabolic syndrome-affected horses.

Conclusion

  • The findings suggest that metformin may be used as a preconditioning agent, essentially preparing and enhancing the cells for better growth and survival.

Cite This Article

APA
Smieszek A, Kornicka K, Szłapka-Kosarzewska J, Androvic P, Valihrach L, Langerova L, Rohlova E, Kubista M, Marycz K. (2019). Metformin Increases Proliferative Activity and Viability of Multipotent Stromal Stem Cells Isolated from Adipose Tissue Derived from Horses with Equine Metabolic Syndrome. Cells, 8(2), 80. https://doi.org/10.3390/cells8020080

Publication

Cells
ISSN: 2073-4409
NlmUniqueID: 101600052
Country: Switzerland
Language: English
Volume: 8
Issue: 2
PII: 80

Researcher Affiliations

Smieszek, Agnieszka
  • Department of Experimental Biology, The Faculty of Biology and Animal Science, University of Environmental and Life Sciences, 50-375 Wroclaw, Poland. agnieszka.smieszek@upwr.edu.pl.
Kornicka, Katarzyna
  • Department of Experimental Biology, The Faculty of Biology and Animal Science, University of Environmental and Life Sciences, 50-375 Wroclaw, Poland. kornicka.katarzyna@gmail.com.
Szłapka-Kosarzewska, Jolanta
  • Department of Experimental Biology, The Faculty of Biology and Animal Science, University of Environmental and Life Sciences, 50-375 Wroclaw, Poland. jolanta.szlapka@upwr.edu.pl.
Androvic, Peter
  • Laboratory of Gene Expression, Institute of Biotechnology CAS, Biocev, 252 50 Vestec, Czech Republic. peter.androvic@ibt.cas.cz.
  • Laboratory of Growth Regulators, Faculty of Science, Palacky University, 78371 Olomouc, Czech Republic. peter.androvic@ibt.cas.cz.
Valihrach, Lukas
  • Laboratory of Gene Expression, Institute of Biotechnology CAS, Biocev, 252 50 Vestec, Czech Republic. lukas.valihrach@ibt.cas.cz.
Langerova, Lucie
  • Gene Core BIOCEV, Průmyslová 595, Vestec 252 50, Czech Republic. krzysztof.marycz@upwr.edu.pl.
Rohlova, Eva
  • Laboratory of Gene Expression, Institute of Biotechnology CAS, Biocev, 252 50 Vestec, Czech Republic. eva.rohlova@ibt.cas.cz.
  • Department of Anthropology and Human Genetics, Faculty of Science, Charles University, 128 43 Prague, Czech Republic. eva.rohlova@ibt.cas.cz.
Kubista, Mikael
  • Laboratory of Gene Expression, Institute of Biotechnology CAS, Biocev, 252 50 Vestec, Czech Republic. mikael.kubista@tataa.com.
  • TATAA Biocenter AB, 411 03 Gothenburg, Sweden. mikael.kubista@tataa.com.
Marycz, Krzysztof
  • Department of Experimental Biology, The Faculty of Biology and Animal Science, University of Environmental and Life Sciences, 50-375 Wroclaw, Poland. mikael.kubista@ibt.cas.cz.
  • Faculty of Veterinary Medicine, Equine Clinic-Equine Surgery, Justus-Liebig-University, 35392 Giessen, Germany. mikael.kubista@ibt.cas.cz.

MeSH Terms

  • Adipose Tissue / cytology
  • Animals
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Cell Separation
  • Cell Survival / drug effects
  • Cells, Cultured
  • Horses
  • Membrane Potential, Mitochondrial / drug effects
  • Metabolic Syndrome / drug therapy
  • Metabolic Syndrome / pathology
  • Metabolic Syndrome / veterinary
  • Metformin / pharmacology
  • Metformin / therapeutic use
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Multipotent Stem Cells / cytology
  • Oxidation-Reduction
  • Wnt3A Protein / metabolism
  • beta Catenin / metabolism

Conflict of Interest Statement

M.K has shares in TATAA Biocenter. The authors declare no conflict of interest

References

This article includes 83 references
  1. Pagan JD, Martin OA, Crowley NL. Relationship Between Body Condition and Metabolic Parameters in Sport Horses, Pony Hunters and Polo Ponies. J. Equine Vet. Sci. 2009;29:418–420.
    doi: 10.1016/j.jevs.2009.04.117google scholar: lookup
  2. Basinska K, Marycz K, Śieszek A, Nicpoń J. The production and distribution of IL-6 and TNF-a in subcutaneous adipose tissue and their correlation with serum concentrations in Welsh ponies with equine metabolic syndrome.. J Vet Sci 2015;16(1):113-20.
    doi: 10.4142/jvs.2015.16.1.113pmc: PMC4367141pubmed: 25269712google scholar: lookup
  3. Marycz K, Kornicka K, Basinska K, Czyrek A. 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.
    doi: 10.1155/2016/4710326pmc: PMC4670679pubmed: 26682006google scholar: lookup
  4. Marycz K, Weiss C, Śmieszek A, Kornicka K. Evaluation of Oxidative Stress and Mitophagy during Adipogenic Differentiation of Adipose-Derived Stem Cells Isolated from Equine Metabolic Syndrome (EMS) Horses.. Stem Cells Int 2018;2018:5340756.
    doi: 10.1155/2018/5340756pmc: PMC6011082pubmed: 29977307google scholar: lookup
  5. Marycz K, Kornicka K, Grzesiak J, Śmieszek A, Szłapka J. Macroautophagy and Selective Mitophagy Ameliorate Chondrogenic Differentiation Potential in Adipose Stem Cells of Equine Metabolic Syndrome: New Findings in the Field of Progenitor Cells Differentiation.. Oxid Med Cell Longev 2016;2016:3718468.
    doi: 10.1155/2016/3718468pmc: PMC5178365pubmed: 28053691google scholar: lookup
  6. Ranera B, Remacha AR, Álvarez-Arguedas S, Romero A, Vázquez FJ, Zaragoza P, Martín-Burriel I, Rodellar C. Effect of hypoxia on equine mesenchymal stem cells derived from bone marrow and adipose tissue.. BMC Vet Res 2012 Aug 22;8:142.
    doi: 10.1186/1746-6148-8-142pmc: PMC3483288pubmed: 22913590google scholar: lookup
  7. Del Bue M, Riccò S, Ramoni R, Conti V, Gnudi G, Grolli S. Equine adipose-tissue derived mesenchymal stem cells and platelet concentrates: their association in vitro and in vivo.. Vet Res Commun 2008 Sep;32 Suppl 1:S51-5.
    doi: 10.1007/s11259-008-9093-3pubmed: 18683070google scholar: lookup
  8. Nicpoń J, Marycz K, Grzesiak J. Therapeutic effect of adipose-derived mesenchymal stem cell injection in horses suffering from bone spavin.. Pol J Vet Sci 2013;16(4):753-4.
    doi: 10.2478/pjvs-2013-0107pubmed: 24597313google scholar: lookup
  9. Marycz K, Toker NY, Grzesiak J, Wrzeszcz K. The Therapeutic Effect of Autogenic Adipose Derived Stem Cells Combined with Autogenic Platelet Rich Plasma in Tendons Disorders in Horses In Vitro and In Vivo Research. J. Anim. Vet. Adv. 2012;11:4324–4331.
  10. Gnecchi M, Zhang Z, Ni A, Dzau VJ. Paracrine mechanisms in adult stem cell signaling and therapy.. Circ Res 2008 Nov 21;103(11):1204-19.
    doi: 10.1161/CIRCRESAHA.108.176826pmc: PMC2667788pubmed: 19028920google scholar: lookup
  11. de Aro AA, Carneiro GD, Teodoro LFR, da Veiga FC, Ferrucci DL, Simões GF, Simões PW, Alvares LE, de Oliveira ALR, Vicente CP, Gomes CP, Pesquero JB, Esquisatto MAM, de Campos Vidal B, Pimentel ER. Injured Achilles Tendons Treated with Adipose-Derived Stem Cells Transplantation and GDF-5.. Cells 2018 Aug 31;7(9).
    doi: 10.3390/cells7090127pmc: PMC6162699pubmed: 30200326google scholar: lookup
  12. Marędziak M, Marycz K, Lewandowski D, Siudzińska A, Śmieszek A. Static magnetic field enhances synthesis and secretion of membrane-derived microvesicles (MVs) rich in VEGF and BMP-2 in equine adipose-derived stromal cells (EqASCs)-a new approach in veterinary regenerative medicine.. In Vitro Cell Dev Biol Anim 2015 Mar;51(3):230-40.
    doi: 10.1007/s11626-014-9828-0pmc: PMC4368852pubmed: 25428200google scholar: lookup
  13. Kornicka K, Marycz K, Tomaszewski KA, Marędziak M, Śmieszek A. The Effect of Age on Osteogenic and Adipogenic Differentiation Potential of Human Adipose Derived Stromal Stem Cells (hASCs) and the Impact of Stress Factors in the Course of the Differentiation Process.. Oxid Med Cell Longev 2015;2015:309169.
    doi: 10.1155/2015/309169pmc: PMC4515302pubmed: 26246868google scholar: lookup
  14. Nawrocka D, Kornicka K, Szydlarska J, Marycz K. Basic Fibroblast Growth Factor Inhibits Apoptosis and Promotes Proliferation of Adipose-Derived Mesenchymal Stromal Cells Isolated from Patients with Type 2 Diabetes by Reducing Cellular Oxidative Stress.. Oxid Med Cell Longev 2017;2017:3027109.
    pmc: PMC5267085pubmed: 28168007doi: 10.1155/2017/3027109google scholar: lookup
  15. Wu W, Niklason L, Steinbacher DM. The effect of age on human adipose-derived stem cells.. Plast Reconstr Surg 2013 Jan;131(1):27-37.
    doi: 10.1097/PRS.0b013e3182729cfcpubmed: 22965240google scholar: lookup
  16. Liu M, Lei H, Dong P, Fu X, Yang Z, Yang Y, Ma J, Liu X, Cao Y, Xiao R. Adipose-Derived Mesenchymal Stem Cells from the Elderly Exhibit Decreased Migration and Differentiation Abilities with Senescent Properties.. Cell Transplant 2017 Sep;26(9):1505-1519.
    doi: 10.1177/0963689717721221pmc: PMC5680952pubmed: 29113467google scholar: lookup
  17. Geburek F, Roggel F, van Schie HTM, Beineke A, Estrada R, Weber K, Hellige M, Rohn K, Jagodzinski M, Welke B, Hurschler C, Conrad S, Skutella T, van de Lest C, van Weeren R, Stadler PM. Effect of single intralesional treatment of surgically induced equine superficial digital flexor tendon core lesions with adipose-derived mesenchymal stromal cells: a controlled experimental trial.. Stem Cell Res Ther 2017 Jun 5;8(1):129.
    doi: 10.1186/s13287-017-0564-8pmc: PMC5460527pubmed: 28583184google scholar: lookup
  18. De Mattos Carvalho A, Alves ALG, de Oliveira PGG, Cisneros Álvarez LE, Amorim RL, Hussni CA, Deffune E. Use of Adipose Tissue-Derived Mesenchymal Stem Cells for Experimental Tendinitis Therapy in Equines. J. Equine Vet. Sci. 2011;31:26–34.
    doi: 10.1016/j.jevs.2010.11.014google scholar: lookup
  19. Kornicka K, Śmieszek A, Węgrzyn AS, Röcken M, Marycz K. Immunomodulatory Properties of Adipose-Derived Stem Cells Treated with 5-Azacytydine and Resveratrol on Peripheral Blood Mononuclear Cells and Macrophages in Metabolic Syndrome Animals.. J Clin Med 2018 Oct 24;7(11).
    doi: 10.3390/jcm7110383pmc: PMC6262510pubmed: 30356025google scholar: lookup
  20. Kornicka K, Szłapka-Kosarzewska J, Śmieszek A, Marycz K. 5-Azacytydine and resveratrol reverse senescence and ageing of adipose stem cells via modulation of mitochondrial dynamics and autophagy.. J Cell Mol Med 2019 Jan;23(1):237-259.
    doi: 10.1111/jcmm.13914pmc: PMC6307768pubmed: 30370650google scholar: lookup
  21. Marycz K, Tomaszewski KA, Kornicka K, Henry BM, Wroński S, Tarasiuk J, Maredziak M. Metformin Decreases Reactive Oxygen Species, Enhances Osteogenic Properties of Adipose-Derived Multipotent Mesenchymal Stem Cells In Vitro, and Increases Bone Density In Vivo.. Oxid Med Cell Longev 2016;2016:9785890.
    doi: 10.1155/2016/9785890pmc: PMC4852347pubmed: 27195075google scholar: lookup
  22. Śmieszek A, Stręk Z, Kornicka K, Grzesiak J, Weiss C, Marycz K. Antioxidant and Anti-Senescence Effect of Metformin on Mouse Olfactory Ensheathing Cells (mOECs) May Be Associated with Increased Brain-Derived Neurotrophic Factor Levels-An Ex Vivo Study.. Int J Mol Sci 2017 Apr 20;18(4).
    doi: 10.3390/ijms18040872pmc: PMC5412453pubmed: 28425952google scholar: lookup
  23. Qi T, Chen Y, Li H, Pei Y, Woo SL, Guo X, Zhao J, Qian X, Awika J, Huo Y, Wu C. A role for PFKFB3/iPFK2 in metformin suppression of adipocyte inflammatory responses.. J Mol Endocrinol 2017 Jul;59(1):49-59.
    doi: 10.1530/JME-17-0066pmc: PMC5512603pubmed: 28559290google scholar: lookup
  24. Kim EK, Lee SH, Jhun JY, Byun JK, Jeong JH, Lee SY, Kim JK, Choi JY, Cho ML. Metformin Prevents Fatty Liver and Improves Balance of White/Brown Adipose in an Obesity Mouse Model by Inducing FGF21.. Mediators Inflamm 2016;2016:5813030.
    doi: 10.1155/2016/5813030pmc: PMC4745345pubmed: 27057099google scholar: lookup
  25. Schosserer M, Grillari J, Wolfrum C, Scheideler M. Age-Induced Changes in White, Brite, and Brown Adipose Depots: A Mini-Review.. Gerontology 2018;64(3):229-236.
    doi: 10.1159/000485183pubmed: 29212073google scholar: lookup
  26. Rendle DI, Rutledge F, Hughes KJ, Heller J, Durham AE. Effects of metformin hydrochloride on blood glucose and insulin responses to oral dextrose in horses.. Equine Vet J 2013 Nov;45(6):751-4.
    doi: 10.1111/evj.12068pubmed: 23600690google scholar: lookup
  27. Durham AE, Rendle DI, Newton JE. The effect of metformin on measurements of insulin sensitivity and beta cell response in 18 horses and ponies with insulin resistance.. Equine Vet J 2008 Jul;40(5):493-500.
    doi: 10.2746/042516408X273648pubmed: 18482898google scholar: lookup
  28. Tinworth KD, Edwards S, Noble GK, Harris PA, Sillence MN, Hackett LP. Pharmacokinetics of metformin after enteral administration in insulin-resistant ponies.. Am J Vet Res 2010 Oct;71(10):1201-6.
    doi: 10.2460/ajvr.71.10.1201pubmed: 20919907google scholar: lookup
  29. Tinworth KD, Boston RC, Harris PA, Sillence MN, Raidal SL, Noble GK. The effect of oral metformin on insulin sensitivity in insulin-resistant ponies.. Vet J 2012 Jan;191(1):79-84.
    doi: 10.1016/j.tvjl.2011.01.015pubmed: 21349749google scholar: lookup
  30. Barzilai N, Crandall JP, Kritchevsky SB, Espeland MA. Metformin as a Tool to Target Aging.. Cell Metab 2016 Jun 14;23(6):1060-1065.
    doi: 10.1016/j.cmet.2016.05.011pmc: PMC5943638pubmed: 27304507google scholar: lookup
  31. Androvic P, Valihrach L, Elling J, Sjoback R, Kubista M. Two-tailed RT-qPCR: a novel method for highly accurate miRNA quantification.. Nucleic Acids Res 2017 Sep 6;45(15):e144.
    doi: 10.1093/nar/gkx588pmc: PMC5587787pubmed: 28911110google scholar: lookup
  32. Subramaniam N, Sherman MH, Rao R, Wilson C, Coulter S, Atkins AR, Evans RM, Liddle C, Downes M. Metformin-mediated Bambi expression in hepatic stellate cells induces prosurvival Wnt/β-catenin signaling.. Cancer Prev Res (Phila) 2012 Apr;5(4):553-61.
    doi: 10.1158/1940-6207.CAPR-12-0053pmc: PMC3324648pubmed: 22406377google scholar: lookup
  33. Nawrocka D, Kornicka K, Śmieszek A, Marycz K. Spirulina platensis Improves Mitochondrial Function Impaired by Elevated Oxidative Stress in Adipose-Derived Mesenchymal Stromal Cells (ASCs) and Intestinal Epithelial Cells (IECs), and Enhances Insulin Sensitivity in Equine Metabolic Syndrome (EMS) Horses.. Mar Drugs 2017 Aug 3;15(8).
    doi: 10.3390/md15080237pmc: PMC5577592pubmed: 28771165google scholar: lookup
  34. Marędziak M, Marycz K, Smieszek A, Lewandowski D, Toker NY. The influence of static magnetic fields on canine and equine mesenchymal stem cells derived from adipose tissue.. In Vitro Cell Dev Biol Anim 2014 Jun;50(6):562-71.
    doi: 10.1007/s11626-013-9730-1pmc: PMC4062816pubmed: 24477562google scholar: lookup
  35. Marycz K, Krzak-Roś J, Donesz-Sikorska A, Śmieszek A. The morphology, proliferation rate, and population doubling time factor of adipose-derived mesenchymal stem cells cultured on to non-aqueous SiO2, TiO2, and hybrid sol-gel-derived oxide coatings.. J Biomed Mater Res A 2014 Nov;102(11):4017-26.
    doi: 10.1002/jbm.a.35072pubmed: 24408867google scholar: lookup
  36. Nowak U, Marycz K, Nicpoń J, Śmieszek A. Chondrogenic potential of canine articular cartilage derived cells (cACCs). Open Life Sci. 2016;11:151–165.
    doi: 10.1515/biol-2016-0021google scholar: lookup
  37. Marycz K, Michalak I, Kocherova I, Marędziak M, Weiss C. The Cladophora glomerata Enriched by Biosorption Process in Cr(III) Improves Viability, and Reduces Oxidative Stress and Apoptosis in Equine Metabolic Syndrome Derived Adipose Mesenchymal Stromal Stem Cells (ASCs) and Their Extracellular Vesicles (MV's).. Mar Drugs 2017 Dec 8;15(12).
    doi: 10.3390/md15120385pmc: PMC5742845pubmed: 29292726google scholar: lookup
  38. Marycz K, Sobierajska P, Smieszek A, Maredziak M, Wiglusz K, Wiglusz RJ. Li(+) activated nanohydroxyapatite doped with Eu(3+) ions enhances proliferative activity and viability of human stem progenitor cells of adipose tissue and olfactory ensheathing cells. Further perspective of nHAP:Li(+), Eu(3+) application in theranostics.. Mater Sci Eng C Mater Biol Appl 2017 Sep 1;78:151-162.
    doi: 10.1016/j.msec.2017.04.041pubmed: 28575969google scholar: lookup
  39. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.. Anal Biochem 1987 Apr;162(1):156-9.
    doi: 10.1016/0003-2697(87)90021-2pubmed: 2440339google scholar: lookup
  40. Lis-Bartos A, Smieszek A, Frańczyk K, Marycz K, Lis-Bartos A, Smieszek A, Frańczyk K, Marycz K. Fabrication, Characterization, and Cytotoxicity of Thermoplastic Polyurethane/Poly(lactic acid) Material Using Human Adipose Derived Mesenchymal Stromal Stem Cells (hASCs). Polymers 2018;10:1073.
    doi: 10.3390/polym10101073google scholar: lookup
  41. Marycz K, Kornicka K, Szlapka-Kosarzewska J, Weiss C. Excessive Endoplasmic Reticulum Stress Correlates with Impaired Mitochondrial Dynamics, Mitophagy and Apoptosis, in Liver and Adipose Tissue, but Not in Muscles in EMS Horses.. Int J Mol Sci 2018 Jan 6;19(1).
    doi: 10.3390/ijms19010165pmc: PMC5796114pubmed: 29316632google scholar: lookup
  42. Marycz K, Kornicka K, Marędziak M, Golonka P, Nicpoń J. Equine metabolic syndrome impairs adipose stem cells osteogenic differentiation by predominance of autophagy over selective mitophagy.. J Cell Mol Med 2016 Dec;20(12):2384-2404.
    doi: 10.1111/jcmm.12932pmc: PMC5134411pubmed: 27629697google scholar: lookup
  43. Marycz K, Marędziak M, Grzesiak J, Lis A, Śmieszek A, Marycz K, Marędziak M, Grzesiak J, Lis A, Śmieszek A. Biphasic Polyurethane/Polylactide Sponges Doped with Nano-Hydroxyapatite (nHAp) Combined with Human Adipose-Derived Mesenchymal Stromal Stem Cells for Regenerative Medicine Applications. Polymers 2016;8:339.
    doi: 10.3390/polym8100339google scholar: lookup
  44. Dzamba D, Valihrach L, Kubista M, Anderova M. The correlation between expression profiles measured in single cells and in traditional bulk samples.. Sci Rep 2016 Nov 16;6:37022.
    doi: 10.1038/srep37022pmc: PMC5111061pubmed: 27848982google scholar: lookup
  45. Pivonkova H, Hermanova Z, Kirdajova D, Awadova T, Malinsky J, Valihrach L, Zucha D, Kubista M, Galisova A, Jirak D, Anderova M. The Contribution of TRPV4 Channels to Astrocyte Volume Regulation and Brain Edema Formation.. Neuroscience 2018 Dec 1;394:127-143.
    doi: 10.1016/j.neuroscience.2018.10.028pubmed: 30367945google scholar: lookup
  46. 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 Rep 2018 Jun;14(3):337-345.
    doi: 10.1007/s12015-018-9809-xpmc: PMC5960487pubmed: 29611042google scholar: lookup
  47. Gallagher D, Kelley DE, Yim JE, Spence N, Albu J, Boxt L, Pi-Sunyer FX, Heshka S. Adipose tissue distribution is different in type 2 diabetes.. Am J Clin Nutr 2009 Mar;89(3):807-14.
    pmc: PMC2714397pubmed: 19158213doi: 10.3945/ajcn.2008.26955google scholar: lookup
  48. Lee MJ, Wu Y, Fried SK. Adipose tissue heterogeneity: implication of depot differences in adipose tissue for obesity complications.. Mol Aspects Med 2013 Feb;34(1):1-11.
    doi: 10.1016/j.mam.2012.10.001pmc: PMC3549425pubmed: 23068073google scholar: lookup
  49. Dev R, Bruera E, Dalal S. Insulin resistance and body composition in cancer patients.. Ann Oncol 2018 Feb 1;29(suppl_2):ii18-ii26.
    doi: 10.1093/annonc/mdx815pubmed: 29506229google scholar: lookup
  50. Śmieszek A, Basińska K, Chrząstek K, Marycz K. In Vitro and In Vivo Effects of Metformin on Osteopontin Expression in Mice Adipose-Derived Multipotent Stromal Cells and Adipose Tissue.. J Diabetes Res 2015;2015:814896.
    doi: 10.1155/2015/814896pmc: PMC4430663pubmed: 26064989google scholar: lookup
  51. Baer PC, Geiger H. Adipose-derived mesenchymal stromal/stem cells: tissue localization, characterization, and heterogeneity.. Stem Cells Int 2012;2012:812693.
    doi: 10.1155/2012/812693pmc: PMC3345279pubmed: 22577397google scholar: lookup
  52. Schäfer R, Spohn G, Baer PC. Mesenchymal Stem/Stromal Cells in Regenerative Medicine: Can Preconditioning Strategies Improve Therapeutic Efficacy?. Transfus Med Hemother 2016 Jul;43(4):256-267.
    doi: 10.1159/000447458pmc: PMC5040900pubmed: 27721701google scholar: lookup
  53. Gimble JM, Bunnell BA, Frazier T, Rowan B, Shah F, Thomas-Porch C, Wu X. Adipose-derived stromal/stem cells: a primer.. Organogenesis 2013 Jan-Mar;9(1):3-10.
    doi: 10.4161/org.24279pmc: PMC3674038pubmed: 23538753google scholar: lookup
  54. Baer PC, Overath JM, Urbschat A, Schubert R, Koch B, Bohn AA, Geiger H. Effect of Different Preconditioning Regimens on the Expression Profile of Murine Adipose-Derived Stromal/Stem Cells.. Int J Mol Sci 2018 Jun 10;19(6).
    doi: 10.3390/ijms19061719pmc: PMC6032282pubmed: 29890767google scholar: lookup
  55. . The Pleiotropic Effects of Metformin: Time for Prospective Studies. Cardiovascular Diabetology .
    doi: 10.1186/s12933-015-0273-5google scholar: lookup
  56. Fatt M, Hsu K, He L, Wondisford F, Miller FD, Kaplan DR, Wang J. Metformin Acts on Two Different Molecular Pathways to Enhance Adult Neural Precursor Proliferation/Self-Renewal and Differentiation.. Stem Cell Reports 2015 Dec 8;5(6):988-995.
    doi: 10.1016/j.stemcr.2015.10.014pmc: PMC4682208pubmed: 26677765google scholar: lookup
  57. Śmieszek A, Szydlarska J, Mucha A, Chrapiec M, Marycz K. Enhanced cytocompatibility and osteoinductive properties of sol-gel-derived silica/zirconium dioxide coatings by metformin functionalization.. J Biomater Appl 2017 Nov;32(5):570-586.
    doi: 10.1177/0885328217738006pubmed: 29113566google scholar: lookup
  58. Cortizo AM, Sedlinsky C, McCarthy AD, Blanco A, Schurman L. Osteogenic actions of the anti-diabetic drug metformin on osteoblasts in culture.. Eur J Pharmacol 2006 Apr 24;536(1-2):38-46.
    doi: 10.1016/j.ejphar.2006.02.030pubmed: 16564524google scholar: lookup
  59. Molinuevo MS, Schurman L, McCarthy AD, Cortizo AM, Tolosa MJ, Gangoiti MV, Arnol V, Sedlinsky C. Effect of metformin on bone marrow progenitor cell differentiation: in vivo and in vitro studies.. J Bone Miner Res 2010 Feb;25(2):211-21.
    doi: 10.1359/jbmr.090732pubmed: 19594306google scholar: lookup
  60. Smieszek A, Tomaszewski KA, Kornicka K, Marycz K. Metformin Promotes Osteogenic Differentiation of Adipose-Derived Stromal Cells and Exerts Pro-Osteogenic Effect Stimulating Bone Regeneration.. J Clin Med 2018 Nov 26;7(12).
    doi: 10.3390/jcm7120482pmc: PMC6306720pubmed: 30486321google scholar: lookup
  61. Śmieszek A, Czyrek A, Basinska K, Trynda J, Skaradzińska A, Siudzińska A, Marędziak M, Marycz K. Effect of Metformin on Viability, Morphology, and Ultrastructure of Mouse Bone Marrow-Derived Multipotent Mesenchymal Stromal Cells and Balb/3T3 Embryonic Fibroblast Cell Line.. Biomed Res Int 2015;2015:769402.
    doi: 10.1155/2015/769402pmc: PMC4430655pubmed: 26064951google scholar: lookup
  62. Kheirandish M, Mahboobi H, Yazdanparast M, Kamal W, Kamal MA. Anti-cancer Effects of Metformin: Recent Evidences for its Role in Prevention and Treatment of Cancer.. Curr Drug Metab 2018;19(9):793-797.
    doi: 10.2174/1389200219666180416161846pubmed: 29663879google scholar: lookup
  63. Gomes LC, Di Benedetto G, Scorrano L. During autophagy mitochondria elongate, are spared from degradation and sustain cell viability.. Nat Cell Biol 2011 May;13(5):589-98.
    doi: 10.1038/ncb2220pmc: PMC3088644pubmed: 21478857google scholar: lookup
  64. Wang GY, Bi YG, Liu XD, Zhao Y, Han JF, Wei M, Zhang QY. Autophagy was involved in the protective effect of metformin on hyperglycemia-induced cardiomyocyte apoptosis and Connexin43 downregulation in H9c2 cells.. Int J Med Sci 2017;14(7):698-704.
    doi: 10.7150/ijms.19800pmc: PMC5562122pubmed: 28824303google scholar: lookup
  65. He X, Yao MW, Zhu M, Liang DL, Guo W, Yang Y, Zhao RS, Ren TT, Ao X, Wang W, Zeng CY, Liang HP, Jiang DP, Yu J, Xu X. Metformin induces apoptosis in mesenchymal stromal cells and dampens their therapeutic efficacy in infarcted myocardium.. Stem Cell Res Ther 2018 Nov 8;9(1):306.
    doi: 10.1186/s13287-018-1057-0pmc: PMC6225675pubmed: 30409193google scholar: lookup
  66. Kim JA, Choi HK, Kim TM, Leem SH, Oh IH. Regulation of mesenchymal stromal cells through fine tuning of canonical Wnt signaling.. Stem Cell Res 2015 May;14(3):356-68.
    doi: 10.1016/j.scr.2015.02.007pubmed: 25863444google scholar: lookup
  67. Visweswaran M, Pohl S, Arfuso F, Newsholme P, Dilley R, Pervaiz S, Dharmarajan A. Multi-lineage differentiation of mesenchymal stem cells - To Wnt, or not Wnt.. Int J Biochem Cell Biol 2015 Nov;68:139-47.
    doi: 10.1016/j.biocel.2015.09.008pubmed: 26410622google scholar: lookup
  68. Zhou JY, Xu B, Li L. A New Role for an Old Drug: Metformin Targets MicroRNAs in Treating Diabetes and Cancer.. Drug Dev Res 2015 Sep;76(6):263-9.
    doi: 10.1002/ddr.21265pubmed: 26936407google scholar: lookup
  69. Avci CB, Harman E, Dodurga Y, Susluer SY, Gunduz C. Therapeutic potential of an anti-diabetic drug, metformin: alteration of miRNA expression in prostate cancer cells.. Asian Pac J Cancer Prev 2013;14(2):765-8.
    doi: 10.7314/APJCP.2013.14.2.765pubmed: 23621234google scholar: lookup
  70. Tan K, Peng YT, Guo P. MiR-29a promotes osteogenic differentiation of mesenchymal stem cells via targeting HDAC4.. Eur Rev Med Pharmacol Sci 2018 Jun;22(11):3318-3326.
    pubmed: 29917181doi: 10.26355/eurrev_201806_15151google scholar: lookup
  71. Guo L, Zhao RC, Wu Y. The role of microRNAs in self-renewal and differentiation of mesenchymal stem cells.. Exp Hematol 2011 Jun;39(6):608-16.
    doi: 10.1016/j.exphem.2011.01.011pubmed: 21288479google scholar: lookup
  72. Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. miR-15 and miR-16 induce apoptosis by targeting BCL2.. Proc Natl Acad Sci U S A 2005 Sep 27;102(39):13944-9.
    doi: 10.1073/pnas.0506654102pmc: PMC1236577pubmed: 16166262google scholar: lookup
  73. Zeng YL, Zheng H, Chen QR, Yuan XH, Ren JH, Luo XF, Chen P, Lin ZY, Chen SZ, Wu XQ, Xiao M, Chen YQ, Chen ZZ, Hu JD, Yang T. Bone marrow-derived mesenchymal stem cells overexpressing MiR-21 efficiently repair myocardial damage in rats.. Oncotarget 2017 Apr 25;8(17):29161-29173.
    doi: 10.18632/oncotarget.16254pmc: PMC5438721pubmed: 28418864google scholar: lookup
  74. Sun Y, Xu L, Huang S, Hou Y, Liu Y, Chan KM, Pan XH, Li G. mir-21 overexpressing mesenchymal stem cells accelerate fracture healing in a rat closed femur fracture model.. Biomed Res Int 2015;2015:412327.
    doi: 10.1155/2015/412327pmc: PMC4386680pubmed: 25879024google scholar: lookup
  75. Sugatani T, Vacher J, Hruska KA. A microRNA expression signature of osteoclastogenesis.. Blood 2011 Mar 31;117(13):3648-57.
    doi: 10.1182/blood-2010-10-311415pmc: PMC3072882pubmed: 21273303google scholar: lookup
  76. Mei Y, Bian C, Li J, Du Z, Zhou H, Yang Z, Zhao RC. miR-21 modulates the ERK-MAPK signaling pathway by regulating SPRY2 expression during human mesenchymal stem cell differentiation.. J Cell Biochem 2013 Jun;114(6):1374-84.
    doi: 10.1002/jcb.24479pubmed: 23239100google scholar: lookup
  77. Zhou Y, Liu Y, Cheng L. miR-21 expression is related to particle-induced osteolysis pathogenesis.. J Orthop Res 2012 Nov;30(11):1837-42.
    doi: 10.1002/jor.22128pubmed: 22508494google scholar: lookup
  78. Zhang Y, Zhou S. MicroRNA-29a inhibits mesenchymal stem cell viability and proliferation by targeting Roundabout 1.. Mol Med Rep 2015 Oct;12(4):6178-84.
    doi: 10.3892/mmr.2015.4183pubmed: 26252416google scholar: lookup
  79. Fráguas MS, Eggenschwiler R, Hoepfner J, Schiavinato JLDS, Haddad R, Oliveira LHB, Araújo AG, Zago MA, Panepucci RA, Cantz T. MicroRNA-29 impairs the early phase of reprogramming process by targeting active DNA demethylation enzymes and Wnt signaling.. Stem Cell Res 2017 Mar;19:21-30.
    doi: 10.1016/j.scr.2016.12.020pubmed: 28038351google scholar: lookup
  80. Sun DG, Xin BC, Wu D, Zhou L, Wu HB, Gong W, Lv J. miR-140-5p-mediated regulation of the proliferation and differentiation of human dental pulp stem cells occurs through the lipopolysaccharide/toll-like receptor 4 signaling pathway.. Eur J Oral Sci 2017 Dec;125(6):419-425.
    doi: 10.1111/eos.12384pubmed: 29130547google scholar: lookup
  81. Da Costa Santos H, Hess T, Bruemmer J, Splan R. Possible Role of MicroRNA in Equine Insulin Resistance: A Pilot Study. J. Equine Vet. Sci. 2018;63:74–79.
    doi: 10.1016/j.jevs.2017.10.024google scholar: lookup
  82. Raitoharju E, Seppälä I, Oksala N, Lyytikäinen LP, Raitakari O, Viikari J, Ala-Korpela M, Soininen P, Kangas AJ, Waldenberger M, Klopp N, Illig T, Leiviskä J, Loo BM, Hutri-Kähönen N, Kähönen M, Laaksonen R, Lehtimäki T. Blood microRNA profile associates with the levels of serum lipids and metabolites associated with glucose metabolism and insulin resistance and pinpoints pathways underlying metabolic syndrome: the cardiovascular risk in Young Finns Study.. Mol Cell Endocrinol 2014 Jun 25;391(1-2):41-9.
    doi: 10.1016/j.mce.2014.04.013pubmed: 24784704google scholar: lookup
  83. van der Kolk JH, Pacholewska A, Gerber V. The role of microRNAs in equine medicine: a review.. Vet Q 2015 Jun;35(2):88-96.
    doi: 10.1080/01652176.2015.1021186pubmed: 25695624google scholar: lookup

Citations

This article has been cited 16 times.
  1. Data K, Marcinkowska K, Buś K, Valihrach L, Pawlak E, Śmieszek A. β-Lactoglobulin affects the oxidative status and viability of equine endometrial progenitor cells via lncRNA-mRNA-miRNA regulatory associations.. J Cell Mol Med 2023 Apr;27(7):927-938.
    doi: 10.1111/jcmm.17694pubmed: 36860157google scholar: lookup
  2. Sikora M, Krajewska K, Marcinkowska K, Raciborska A, Wiglusz RJ, Śmieszek A. Comparison of Selected Non-Coding RNAs and Gene Expression Profiles between Common Osteosarcoma Cell Lines.. Cancers (Basel) 2022 Sep 19;14(18).
    doi: 10.3390/cancers14184533pubmed: 36139691google scholar: lookup
  3. Zhang YL, Liu F, Li ZB, He XT, Li X, Wu RX, Sun HH, Ge SH, Chen FM, An Y. Metformin combats high glucose-induced damage to the osteogenic differentiation of human periodontal ligament stem cells via inhibition of the NPR3-mediated MAPK pathway.. Stem Cell Res Ther 2022 Jul 15;13(1):305.
    doi: 10.1186/s13287-022-02992-zpubmed: 35841070google scholar: lookup
  4. Morawska-Kochman M, Śmieszek A, Marcinkowska K, Marycz KM, Nelke K, Zub K, Zatoński T, Bochnia M. Expression of Apoptosis-Related Biomarkers in Inflamed Nasal Sinus Epithelium of Patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)-Evaluation at mRNA and miRNA Levels.. Biomedicines 2022 Jun 13;10(6).
    doi: 10.3390/biomedicines10061400pubmed: 35740420google scholar: lookup
  5. Smieszek A, Marcinkowska K, Pielok A, Sikora M, Valihrach L, Carnevale E, Marycz K. Obesity Affects the Proliferative Potential of Equine Endometrial Progenitor Cells and Modulates Their Molecular Phenotype Associated with Mitochondrial Metabolism.. Cells 2022 Apr 24;11(9).
    doi: 10.3390/cells11091437pubmed: 35563743google scholar: lookup
  6. Chinnapaka S, Yang KS, Flowers Q, Faisal M, Nerone WV, Rubin JP, Ejaz A. Metformin Improves Stemness of Human Adipose-Derived Stem Cells by Downmodulation of Mechanistic Target of Rapamycin (mTOR) and Extracellular Signal-Regulated Kinase (ERK) Signaling.. Biomedicines 2021 Nov 27;9(12).
    doi: 10.3390/biomedicines9121782pubmed: 34944598google scholar: lookup
  7. Le Pelletier L, Mantecon M, Gorwood J, Auclair M, Foresti R, Motterlini R, Laforge M, Atlan M, Fève B, Capeau J, Lagathu C, Bereziat V. Metformin alleviates stress-induced cellular senescence of aging human adipose stromal cells and the ensuing adipocyte dysfunction.. Elife 2021 Sep 21;10.
    doi: 10.7554/eLife.62635pubmed: 34544550google scholar: lookup
  8. Marycz K, Śmieszek A, Kornicka-Garbowska K, Pielok A, Janeczek M, Lipińska A, Nikodem A, Filipiak J, Sobierajska P, Nedelec JM, Wiglusz RJ. Novel Nanohydroxyapatite (nHAp)-Based Scaffold Doped with Iron Oxide Nanoparticles (IO), Functionalized with Small Non-Coding RNA (miR-21/124) Modulates Expression of Runt-Related Transcriptional Factor 2 and Osteopontin, Promoting Regeneration of Osteoporotic Bone in Bilateral Cranial Defects in a Senescence-Accelerated Mouse Model (SAM/P6). PART 2.. Int J Nanomedicine 2021;16:6049-6065.
    doi: 10.2147/IJN.S316240pubmed: 34511905google scholar: lookup
  9. Ribot J, Denoeud C, Frescaline G, Landon R, Petite H, Pavon-Djavid G, Bensidhoum M, Anagnostou F. Experimental Type 2 Diabetes Differently Impacts on the Select Functions of Bone Marrow-Derived Multipotent Stromal Cells.. Cells 2021 Jan 29;10(2).
    doi: 10.3390/cells10020268pubmed: 33572905google scholar: lookup
  10. Jiang LL, Liu L. Effect of metformin on stem cells: Molecular mechanism and clinical prospect.. World J Stem Cells 2020 Dec 26;12(12):1455-1473.
    doi: 10.4252/wjsc.v12.i12.1455pubmed: 33505595google scholar: lookup
  11. Smieszek A, Seweryn A, Marcinkowska K, Sikora M, Lawniczak-Jablonska K, Witkowski BS, Kuzmiuk P, Godlewski M, Marycz K. Titanium Dioxide Thin Films Obtained by Atomic Layer Deposition Promotes Osteoblasts' Viability and Differentiation Potential While Inhibiting Osteoclast Activity-Potential Application for Osteoporotic Bone Regeneration.. Materials (Basel) 2020 Oct 28;13(21).
    doi: 10.3390/ma13214817pubmed: 33126628google scholar: lookup
  12. Gui W, Zhu WF, Zhu Y, Tang S, Zheng F, Yin X, Lin X, Li H. LncRNAH19 improves insulin resistance in skeletal muscle by regulating heterogeneous nuclear ribonucleoprotein A1.. Cell Commun Signal 2020 Oct 28;18(1):173.
    doi: 10.1186/s12964-020-00654-2pubmed: 33115498google scholar: lookup
  13. Baer PC. Adipose-Derived Stromal/Stem Cells.. Cells 2020 Aug 30;9(9).
    doi: 10.3390/cells9091997pubmed: 32872606google scholar: lookup
  14. Seweryn A, Pielok A, Lawniczak-Jablonska K, Pietruszka R, Marcinkowska K, Sikora M, Witkowski BS, Godlewski M, Marycz K, Smieszek A. Zirconium Oxide Thin Films Obtained by Atomic Layer Deposition Technology Abolish the Anti-Osteogenic Effect Resulting from miR-21 Inhibition in the Pre-Osteoblastic MC3T3 Cell Line.. Int J Nanomedicine 2020;15:1595-1610.
    doi: 10.2147/IJN.S237898pubmed: 32210554google scholar: lookup
  15. Smieszek A, Marcinkowska K, Pielok A, Sikora M, Valihrach L, Marycz K. The Role of miR-21 in Osteoblasts-Osteoclasts Coupling In Vitro.. Cells 2020 Feb 19;9(2).
    doi: 10.3390/cells9020479pubmed: 32093031google scholar: lookup
  16. Yao D, Zhan X, Zhan X, Kwoh CK, Sun Y. ncRNA2MetS: a manually curated database for non-coding RNAs associated with metabolic syndrome.. PeerJ 2019;7:e7909.
    doi: 10.7717/peerj.7909pubmed: 31637139google scholar: lookup
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