Effect of glucagon-like peptide-1 on differentiation of adipose derived mesenchymal stem cells into cardiomyocytes

Özgür Tekin; Yiğit Uyanıkgil; Dilek Taşkıran

doi:10.19161/etd.1180666

Research Article

Effect of glucagon-like peptide-1 on differentiation of adipose derived mesenchymal stem cells into cardiomyocytes

Year 2022, Volume: 61 Issue: 4, 507 - 517, 12.12.2022

Özgür Tekin Yiğit Uyanıkgil Dilek Taşkıran

https://doi.org/10.19161/etd.1180666

Abstract

Aim: Mesenchymal stem cells can easily differentiate into cardiomyocytes in vitro conditions using
various protocols. However, the agents used in these protocols have been reported to have some
adverse effects on cell viability. Azacitidine is used to differentiate mesenchymal stem cells into cardiac
muscle cells. The aim of the present study was to investigate the effects of Exenatide a GLP-1 receptor
agonist, on differentiation and viability of human adipose tissue derived stem cells into cardiomyocytes.

Materials and Methods: The effects of Azacytidine and Exenatide on cell viability and proliferation of
human adipose tissue derived stem cells were analyzed with cytotoxicity assay. For differentiation
procedure, of human adipose tissue derived stem cells were incubated with Azacytidine and Exenatide
through four weeks. The morphological alterations of human adipose tissue derived stem cells were
monitored and the expressions of cardiomyogenic differentiation markers (cTnI, GATA4 ve MYH7) were
evaluated immunohistochemically. Also, cardiac troponin I (cTnI) levels in the cultures were measured
using enzyme-linked immunosorbent assay. Results were evaluated by one way analysis of variance
(ANOVA) and post-hoc test.

Results: Treatment of the human adipose tissue derived stem cells with Azacytidine significantly
decreased cell viability (54.4%) compared to control whereas treatment of cells with Azacytidine +
Exenatide prevented cell death in a dose-dependent manner. Cells treated with Azacytidine and
Exenatide showed significant morphological alterations consistent with cardiyomyogenic differentiation,
and increase in expression cardiomyogenic markers. cTnI levels were found significantly higher in
cultures treated separately and together with Azacytidine and Exenatide compared to control.

Conclusion: Overall, these findings suggested that GLP-1 receptor agonist Exenatide may have
beneficial effects on cardiomyogenic differention of human adipose tissue derived stem cells by
reducing cell damage caused by Azacytidine.

Keywords

Adipose tissue derived mesenchymal stem cell, cardiomyocyte, GLP-1

References

Karantalis V, Hare JM. Use of mesenchymal stem cells for therapy of cardiac disease. Circ Res. 2015;116(8):1413-30.
Kim J, Shapiro L, Flynn A. The clinical application of mesenchymal stem cells and cardiac stem cells as a therapy for cardiovascular disease. Pharmacol Ther. 2015;151:8-15.
Sanina C, Hare JM. Mesenchymal Stem Cells as a Biological Drug for Heart Disease: Where Are We With Cardiac Cell-Based Therapy? Circ Res. 2015;117(3):229-33.
Razeghian E, Margiana R, Chupradit S, Bokov DO, Abdelbasset WK, Marofi F, et al. Mesenchymal Stem/Stromal Cells as a Vehicle for Cytokine Delivery: An Emerging Approach for Tumor Immunotherapy. Front Med (Lausanne). 2021;8:721174.
Friedenstein AJ, Chailakhjan RK, Lalykina KS. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet. 1970;3(4):393-403.
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143-7.
Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13(12):4279-95.
De Ugarte DA, Morizono K, Elbarbary A, Alfonso Z, Zuk PA, Zhu M, et al. Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs. 2003;174(3):101-9.
Kassis I, Zangi L, Rivkin R, Levdansky L, Samuel S, Marx G, et al. Isolation of mesenchymal stem cells from G-CSF-mobilized human peripheral blood using fibrin microbeads. Bone Marrow Transplant. 2006;37(10):967-76.
Park YM, Lee M, Jeon S, Hruzova D. In vitro effects of conditioned medium from bioreactor cultured human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on skin-derived cell lines. Regen Ther. 2021;18:281-91.
Antonitsis P, Ioannidou-Papagiannaki E, Kaidoglou A, Papakonstantinou C. In vitro cardiomyogenic differentiation of adult human bone marrow mesenchymal stem cells. The role of 5-azacytidine. Interact Cardiovasc Thorac Surg. 2007;6(5):593-7.
Song K, Wang Z, Li W, Zhang C, Lim M, Liu T. In vitro culture, determination, and directed differentiation of adult adipose-derived stem cells towards cardiomyocyte-like cells induced by angiotensin II. Appl Biochem Biotechnol. 2013;170(2):459-70.
Khajeniazi S, Solati M, Yazdani Y, Soleimani M, Kianmehr A. Synergistic induction of cardiomyocyte differentiation from human bone marrow mesenchymal stem cells by interleukin 1beta and 5-azacytidine. Biol Chem. 2016;397(12):1355-64.
Shi S, Wu X, Wang X, Hao W, Miao H, Zhen L, et al. Differentiation of Bone Marrow Mesenchymal Stem Cells to Cardiomyocyte-Like Cells Is Regulated by the Combined Low Dose Treatment of Transforming Growth Factor-beta1 and 5-Azacytidine. Stem Cells Int. 2016;2016:3816256.
Gasiuniene M, Valatkaite E, Navakauskaite A, Navakauskiene R. The Effect of Angiotensin II, Retinoic Acid, EGCG, and Vitamin C on the Cardiomyogenic Differentiation Induction of Human Amniotic FluidDerived Mesenchymal Stem Cells. Int J Mol Sci. 2020;21(22).
Sorm F, Piskala A, Cihak A, Vesely J. 5-Azacytidine, a new, highly effective cancerostatic. Experientia. 1964;20(4):202-3.
Viegas-Pequignot E, Dutrillaux B. Segmentation of human chromosomes induced by 5-ACR (5- azacytidine). Hum Genet. 1976;34(3):247-54.
Landolph JR, Jones PA. Mutagenicity of 5-azacytidine and related nucleosides in C3H/10T 1/2 clone 8 and V79 cells. Cancer Res. 1982;42(3):817-23.
Makino S, Fukuda K, Miyoshi S, Konishi F, Kodama H, Pan J, et al. Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest. 1999;103(5):697-705.
Joshi J, Brennan D, Beachley V, Kothapalli CR. Cardiomyogenic differentiation of human bone marrowderived mesenchymal stem cell spheroids within electrospun collagen nanofiber mats. J Biomed Mater Res A. 2018;106(12):3303-12.
Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007;87(4):1409-39.
Qian W, Liu F, Yang Q. Effect of glucagon-like peptide-1 receptor agonists in subjects with type 2 diabetes mellitus: A meta-analysis. J Clin Pharm Ther. 2021.
Yun JS, Ko SH. Current trends in epidemiology of cardiovascular disease and cardiovascular risk management in type 2 diabetes. Metabolism. 2021;123:154838.
During MJ, Cao L, Zuzga DS, Francis JS, Fitzsimons HL, Jiao X, et al. Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med. 2003;9(9):1173-9.
Liu J, Wang H, Wang Y, Yin Y, Du Z, Liu Z, et al. The stem cell adjuvant with Exendin-4 repairs the heart after myocardial infarction via STAT3 activation. J Cell Mol Med. 2014;18(7):1381-91.
Zhang H, Xiong Z, Wang J, Zhang S, Lei L, Yang L, et al. Glucagon-like peptide-1 protects cardiomyocytes from advanced oxidation protein product-induced apoptosis via the PI3K/Akt/Bad signaling pathway. Mol Med Rep. 2016;13(2):1593-601.
Sidhu MCAAHBETKS. Role of the Glucagon-like Peptide-1 receptor agonist in maintaining pluripotency in human embryonic stem cells. The Open Stem Cell Journal. 2011;3:11-22.
Lee HM, Joo BS, Lee CH, Kim HY, Ock JH, Lee YS. Effect of Glucagon-like Peptide-1 on the Differentiation of Adipose-derived Stem Cells into Osteoblasts and Adipocytes. J Menopausal Med. 2015;21(2):93-103.
Wang K, Hu W. Oxypaeoniflorin improves myocardial ischemia/reperfusion injury by activating the Sirt1/Foxo1 signaling pathway. Acta Biochim Pol. 2020;67(2):239-45.
Chen JG, Xu XM, Ji H, Sun B. Inhibiting miR-155 protects against myocardial ischemia/reperfusion injury via targeted regulation of HIF-1alpha in rats. Iran J Basic Med Sci. 2019;22(9):1050-8.
Al-Magsoosi MJN, Lambert DW, Ali Khurram S, Whawell SA. Oral cancer stem cells drive tumourigenesis through activation of stromal fibroblasts. Oral Dis. 2021;27(6):1383-93.
Morabito CJ, Kattan J, Bristow J. Mechanisms of embryonic coronary artery development. Curr Opin Cardiol. 2002;17(3):235-41.
Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. 2003;114(6):763-76.
Wagers AJ, Weissman IL. Plasticity of adult stem cells. Cell. 2004;116(5):639-48.
Fraser JK, Schreiber RE, Zuk PA, Hedrick MH. Adult stem cell therapy for the heart. Int J Biochem Cell Biol. 2004;36(4):658-66.
Markmee R, Aungsuchawan S, Tancharoen W, Narakornsak S, Pothacharoen P. Differentiation of cardiomyocyte-like cells from human amniotic fluid mesenchymal stem cells by combined induction with human platelet lysate and 5-azacytidine. Heliyon. 2020;6(9):e04844.
Hassan SSMNH. Combine effect of 5-azacytidine and tgf- β in differentiation of mesenchymal stem cells towards cardiomyocytes. Journal of Stem Cell Research & Therapeutics. 2017;3(1).
Kakkar A, Nandy SB, Gupta S, Bharagava B, Airan B, Mohanty S. Adipose tissue derived mesenchymal stem cells are better respondents to TGFbeta1 for in vitro generation of cardiomyocyte-like cells. Mol Cell Biochem. 2019;460(1-2):53-66.
Perrino C, Rockman HA. GATA4 and the two sides of gene expression reprogramming. Circ Res. 2006;98(6):715-6.
Eden A, Gaudet F, Waghmare A, Jaenisch R. Chromosomal instability and tumors promoted by DNA hypomethylation. Science. 2003;300(5618):455.
De Smet C, Loriot A, Boon T. Promoter-dependent mechanism leading to selective hypomethylation within the 5' region of gene MAGE-A1 in tumor cells. Mol Cell Biol. 2004;24(11):4781-90.
Jackson-Grusby L, Laird PW, Magge SN, Moeller BJ, Jaenisch R. Mutagenicity of 5-aza-2'-deoxycytidine is mediated by the mammalian DNA methyltransferase. Proc Natl Acad Sci U S A. 1997;94(9):4681-5.
Marzioni M, Alpini G, Saccomanno S, Candelaresi C, Venter J, Rychlicki C, et al. Exendin-4, a glucagonlike peptide 1 receptor agonist, protects cholangiocytes from apoptosis. Gut. 2009;58(7):990-7.
Qin Z, Sun Z, Huang J, Hu Y, Wu Z, Mei B. Mutated recombinant human glucagon-like peptide-1 protects SH-SY5Y cells from apoptosis induced by amyloid-beta peptide (1-42). Neurosci Lett. 2008;444(3):217- 21.
Liu JH, Yin F, Guo LX, Deng XH, Hu YH. Neuroprotection of geniposide against hydrogen peroxide induced PC12 cells injury: involvement of PI3 kinase signal pathway. Acta Pharmacol Sin. 2009;30(2):159- 65.
Cunha DA, Ladriere L, Ortis F, Igoillo-Esteve M, Gurzov EN, Lupi R, et al. Glucagon-like peptide-1 agonists protect pancreatic beta-cells from lipotoxic endoplasmic reticulum stress through upregulation of BiP and JunB. Diabetes. 2009;58(12):2851-62.
Blandino-Rosano M, Perez-Arana G, Mellado-Gil JM, Segundo C, Aguilar-Diosdado M. Anti-proliferative effect of pro-inflammatory cytokines in cultured beta cells is associated with extracellular signal-regulated kinase 1/2 pathway inhibition: protective role of glucagon-like peptide -1. J Mol Endocrinol. 2008;41(1):35- 44.
Khalilnezhad A, Taskiran D. The investigation of protective effects of glucagon-like peptide-1 (GLP-1) analogue exenatide against glucose and fructose-induced neurotoxicity. Int J Neurosci. 2019;129(5):481- 91.
Timmers L, Henriques JP, de Kleijn DP, Devries JH, Kemperman H, Steendijk P, et al. Exenatide reduces infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury. J Am Coll Cardiol. 2009;53(6):501-10.
Lonborg J, Vejlstrup N, Kelbaek H, Botker HE, Kim WY, Mathiasen AB, et al. Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction. Eur Heart J. 2012;33(12):1491-9.
Ussher JR, Drucker DJ. Cardiovascular actions of incretin-based therapies. Circ Res. 2014;114(11):1788- 803.
Basalay MV, Mastitskaya S, Mrochek A, Ackland GL, Del Arroyo AG, Sanchez J, et al. Glucagon-like peptide-1 (GLP-1) mediates cardioprotection by remote ischaemic conditioning. Cardiovasc Res. 2016;112(3):669-76.
Wright EJ, Hodson NW, Sherratt MJ, Kassem M, Lewis AL, Wallrapp C, et al. Combined MSC and GLP-1 Therapy Modulates Collagen Remodeling and Apoptosis following Myocardial Infarction. Stem Cells Int. 2016;2016:7357096.
Fukuda K. Molecular characterization of regenerated cardiomyocytes derived from adult mesenchymal stem cells. Congenit Anom (Kyoto). 2002;42(1):1-9.
Liu Y, Song J, Liu W, Wan Y, Chen X, Hu C. Growth and differentiation of rat bone marrow stromal cells: does 5-azacytidine trigger their cardiomyogenic differentiation? Cardiovasc Res. 2003;58(2):460-8.
Lee WC, Sepulveda JL, Rubin JP, Marra KG. Cardiomyogenic differentiation potential of human adipose precursor cells. Int J Cardiol. 2009;133(3):399-401.

Glukagon benzeri peptit-1'in yağ doku kaynaklı mezenkimal kök hücrelerinin kardiyomiyositlere dönüşmesi üzerindeki etkisi

Year 2022, Volume: 61 Issue: 4, 507 - 517, 12.12.2022

Özgür Tekin Yiğit Uyanıkgil Dilek Taşkıran

https://doi.org/10.19161/etd.1180666

Abstract

Amaç: Mezenkimal kök hücreler, çeşitli protokoller kullanılarak in vitro koşullarda kolaylıkla
kardiyomiyositlere farklılaşabilir. Ancak bu protokollerde kullanılan ajanların hücre canlılığı üzerinde bazı
olumsuz etkileri olduğu bildirilmiştir. Azasitidin mezenkimal kök hücreleri kalp kası hücrelerine
farklandırmak için kullanılmaktadır. Bu çalışmanın amacı, bir GLP-1 reseptör agonisti olan Eksenatid'in
insan yağ dokusu kaynaklı kök hücrelerinin kardiyomiyositlere farklılaşması ve canlılığı üzerindeki
etkilerini araştırmaktır.

Gereç ve Yöntem: Azasitidin ve Eksenatid'in insan yağ doku kaynaklı mezenkimal kök hücreler
üzerinde hücre canlılığı ve proliferasyonu üzerindeki etkileri ile sitotoksisite testleri yapıldı. Farklılanma
protokolü için, hücreler dört hafta boyunca Azasitidin ve Eksenatid ile inkübe edildi. Hücrelerin morfolojik
değişiklikleri izlendi ve kardiyomiyojenik farklılaşma belirteçlerinin (cTnI, GATA4 ve MYH7)
ekspresyonları immünohistokimyasal olarak değerlendirildi. Ayrıca kültürlerdeki kardiyak troponin I
(cTnI) seviyeleri enzime bağlı immünosorbent testi kullanılarak ölçüldü. Veriler, tek yönlü varyans analizi
(ANOVA) ve post-hoc testi ile değerlendirildi.

Bulgular: İnsan yağ doku kaynaklı mezenkimal kök hücreler üzerine Azasitidin uygulaması, kontrole
grubuna kıyasla hücre canlılığını önemli ölçüde azaltırken (%54.4) hücrelerin Azasitidin+Eksenatid ile
uygulaması doza bağlı bir şekilde hücre ölümünü önledi. Azasitidin ve Eksenatid uygulanan hücreler,
kardiyomiyojenik farklılaşma ile uyumlu önemli morfolojik değişiklikler ve kardiyomiyojenik belirteçlerde
artış gösterdi. Ayrı ayrı ve birlikte uygulama yapılan gruplarda cTnI seviyeleri kontrole göre anlamlı
derecede yüksek bulundu.

Sonuç: Bu bulgular GLP-1 reseptör agonisti Eksenatid'in, Azasitidin uygulamasının neden olduğu hücre
hasarını azaltarak İnsan yağ doku kaynaklı mezenkimal kök hücrelerin kardiyomiyojenik farklılaşması
üzerinde faydalı etkileri olabileceğini düşündürmektedir.

Keywords

Yağ doku kaynaklı mezenkimal kök hücre, kardiyomiyosit, GLP-1.

References

Karantalis V, Hare JM. Use of mesenchymal stem cells for therapy of cardiac disease. Circ Res. 2015;116(8):1413-30.
Kim J, Shapiro L, Flynn A. The clinical application of mesenchymal stem cells and cardiac stem cells as a therapy for cardiovascular disease. Pharmacol Ther. 2015;151:8-15.
Sanina C, Hare JM. Mesenchymal Stem Cells as a Biological Drug for Heart Disease: Where Are We With Cardiac Cell-Based Therapy? Circ Res. 2015;117(3):229-33.
Razeghian E, Margiana R, Chupradit S, Bokov DO, Abdelbasset WK, Marofi F, et al. Mesenchymal Stem/Stromal Cells as a Vehicle for Cytokine Delivery: An Emerging Approach for Tumor Immunotherapy. Front Med (Lausanne). 2021;8:721174.
Friedenstein AJ, Chailakhjan RK, Lalykina KS. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet. 1970;3(4):393-403.
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143-7.
Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13(12):4279-95.
De Ugarte DA, Morizono K, Elbarbary A, Alfonso Z, Zuk PA, Zhu M, et al. Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs. 2003;174(3):101-9.
Kassis I, Zangi L, Rivkin R, Levdansky L, Samuel S, Marx G, et al. Isolation of mesenchymal stem cells from G-CSF-mobilized human peripheral blood using fibrin microbeads. Bone Marrow Transplant. 2006;37(10):967-76.
Park YM, Lee M, Jeon S, Hruzova D. In vitro effects of conditioned medium from bioreactor cultured human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on skin-derived cell lines. Regen Ther. 2021;18:281-91.
Antonitsis P, Ioannidou-Papagiannaki E, Kaidoglou A, Papakonstantinou C. In vitro cardiomyogenic differentiation of adult human bone marrow mesenchymal stem cells. The role of 5-azacytidine. Interact Cardiovasc Thorac Surg. 2007;6(5):593-7.
Song K, Wang Z, Li W, Zhang C, Lim M, Liu T. In vitro culture, determination, and directed differentiation of adult adipose-derived stem cells towards cardiomyocyte-like cells induced by angiotensin II. Appl Biochem Biotechnol. 2013;170(2):459-70.
Khajeniazi S, Solati M, Yazdani Y, Soleimani M, Kianmehr A. Synergistic induction of cardiomyocyte differentiation from human bone marrow mesenchymal stem cells by interleukin 1beta and 5-azacytidine. Biol Chem. 2016;397(12):1355-64.
Shi S, Wu X, Wang X, Hao W, Miao H, Zhen L, et al. Differentiation of Bone Marrow Mesenchymal Stem Cells to Cardiomyocyte-Like Cells Is Regulated by the Combined Low Dose Treatment of Transforming Growth Factor-beta1 and 5-Azacytidine. Stem Cells Int. 2016;2016:3816256.
Gasiuniene M, Valatkaite E, Navakauskaite A, Navakauskiene R. The Effect of Angiotensin II, Retinoic Acid, EGCG, and Vitamin C on the Cardiomyogenic Differentiation Induction of Human Amniotic FluidDerived Mesenchymal Stem Cells. Int J Mol Sci. 2020;21(22).
Sorm F, Piskala A, Cihak A, Vesely J. 5-Azacytidine, a new, highly effective cancerostatic. Experientia. 1964;20(4):202-3.
Viegas-Pequignot E, Dutrillaux B. Segmentation of human chromosomes induced by 5-ACR (5- azacytidine). Hum Genet. 1976;34(3):247-54.
Landolph JR, Jones PA. Mutagenicity of 5-azacytidine and related nucleosides in C3H/10T 1/2 clone 8 and V79 cells. Cancer Res. 1982;42(3):817-23.
Makino S, Fukuda K, Miyoshi S, Konishi F, Kodama H, Pan J, et al. Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest. 1999;103(5):697-705.
Joshi J, Brennan D, Beachley V, Kothapalli CR. Cardiomyogenic differentiation of human bone marrowderived mesenchymal stem cell spheroids within electrospun collagen nanofiber mats. J Biomed Mater Res A. 2018;106(12):3303-12.
Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007;87(4):1409-39.
Qian W, Liu F, Yang Q. Effect of glucagon-like peptide-1 receptor agonists in subjects with type 2 diabetes mellitus: A meta-analysis. J Clin Pharm Ther. 2021.
Yun JS, Ko SH. Current trends in epidemiology of cardiovascular disease and cardiovascular risk management in type 2 diabetes. Metabolism. 2021;123:154838.
During MJ, Cao L, Zuzga DS, Francis JS, Fitzsimons HL, Jiao X, et al. Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med. 2003;9(9):1173-9.
Liu J, Wang H, Wang Y, Yin Y, Du Z, Liu Z, et al. The stem cell adjuvant with Exendin-4 repairs the heart after myocardial infarction via STAT3 activation. J Cell Mol Med. 2014;18(7):1381-91.
Zhang H, Xiong Z, Wang J, Zhang S, Lei L, Yang L, et al. Glucagon-like peptide-1 protects cardiomyocytes from advanced oxidation protein product-induced apoptosis via the PI3K/Akt/Bad signaling pathway. Mol Med Rep. 2016;13(2):1593-601.
Sidhu MCAAHBETKS. Role of the Glucagon-like Peptide-1 receptor agonist in maintaining pluripotency in human embryonic stem cells. The Open Stem Cell Journal. 2011;3:11-22.
Lee HM, Joo BS, Lee CH, Kim HY, Ock JH, Lee YS. Effect of Glucagon-like Peptide-1 on the Differentiation of Adipose-derived Stem Cells into Osteoblasts and Adipocytes. J Menopausal Med. 2015;21(2):93-103.
Wang K, Hu W. Oxypaeoniflorin improves myocardial ischemia/reperfusion injury by activating the Sirt1/Foxo1 signaling pathway. Acta Biochim Pol. 2020;67(2):239-45.
Chen JG, Xu XM, Ji H, Sun B. Inhibiting miR-155 protects against myocardial ischemia/reperfusion injury via targeted regulation of HIF-1alpha in rats. Iran J Basic Med Sci. 2019;22(9):1050-8.
Al-Magsoosi MJN, Lambert DW, Ali Khurram S, Whawell SA. Oral cancer stem cells drive tumourigenesis through activation of stromal fibroblasts. Oral Dis. 2021;27(6):1383-93.
Morabito CJ, Kattan J, Bristow J. Mechanisms of embryonic coronary artery development. Curr Opin Cardiol. 2002;17(3):235-41.
Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. 2003;114(6):763-76.
Wagers AJ, Weissman IL. Plasticity of adult stem cells. Cell. 2004;116(5):639-48.
Fraser JK, Schreiber RE, Zuk PA, Hedrick MH. Adult stem cell therapy for the heart. Int J Biochem Cell Biol. 2004;36(4):658-66.
Markmee R, Aungsuchawan S, Tancharoen W, Narakornsak S, Pothacharoen P. Differentiation of cardiomyocyte-like cells from human amniotic fluid mesenchymal stem cells by combined induction with human platelet lysate and 5-azacytidine. Heliyon. 2020;6(9):e04844.
Hassan SSMNH. Combine effect of 5-azacytidine and tgf- β in differentiation of mesenchymal stem cells towards cardiomyocytes. Journal of Stem Cell Research & Therapeutics. 2017;3(1).
Kakkar A, Nandy SB, Gupta S, Bharagava B, Airan B, Mohanty S. Adipose tissue derived mesenchymal stem cells are better respondents to TGFbeta1 for in vitro generation of cardiomyocyte-like cells. Mol Cell Biochem. 2019;460(1-2):53-66.
Perrino C, Rockman HA. GATA4 and the two sides of gene expression reprogramming. Circ Res. 2006;98(6):715-6.
Eden A, Gaudet F, Waghmare A, Jaenisch R. Chromosomal instability and tumors promoted by DNA hypomethylation. Science. 2003;300(5618):455.
De Smet C, Loriot A, Boon T. Promoter-dependent mechanism leading to selective hypomethylation within the 5' region of gene MAGE-A1 in tumor cells. Mol Cell Biol. 2004;24(11):4781-90.
Jackson-Grusby L, Laird PW, Magge SN, Moeller BJ, Jaenisch R. Mutagenicity of 5-aza-2'-deoxycytidine is mediated by the mammalian DNA methyltransferase. Proc Natl Acad Sci U S A. 1997;94(9):4681-5.
Marzioni M, Alpini G, Saccomanno S, Candelaresi C, Venter J, Rychlicki C, et al. Exendin-4, a glucagonlike peptide 1 receptor agonist, protects cholangiocytes from apoptosis. Gut. 2009;58(7):990-7.
Qin Z, Sun Z, Huang J, Hu Y, Wu Z, Mei B. Mutated recombinant human glucagon-like peptide-1 protects SH-SY5Y cells from apoptosis induced by amyloid-beta peptide (1-42). Neurosci Lett. 2008;444(3):217- 21.
Liu JH, Yin F, Guo LX, Deng XH, Hu YH. Neuroprotection of geniposide against hydrogen peroxide induced PC12 cells injury: involvement of PI3 kinase signal pathway. Acta Pharmacol Sin. 2009;30(2):159- 65.
Cunha DA, Ladriere L, Ortis F, Igoillo-Esteve M, Gurzov EN, Lupi R, et al. Glucagon-like peptide-1 agonists protect pancreatic beta-cells from lipotoxic endoplasmic reticulum stress through upregulation of BiP and JunB. Diabetes. 2009;58(12):2851-62.
Blandino-Rosano M, Perez-Arana G, Mellado-Gil JM, Segundo C, Aguilar-Diosdado M. Anti-proliferative effect of pro-inflammatory cytokines in cultured beta cells is associated with extracellular signal-regulated kinase 1/2 pathway inhibition: protective role of glucagon-like peptide -1. J Mol Endocrinol. 2008;41(1):35- 44.
Khalilnezhad A, Taskiran D. The investigation of protective effects of glucagon-like peptide-1 (GLP-1) analogue exenatide against glucose and fructose-induced neurotoxicity. Int J Neurosci. 2019;129(5):481- 91.
Timmers L, Henriques JP, de Kleijn DP, Devries JH, Kemperman H, Steendijk P, et al. Exenatide reduces infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury. J Am Coll Cardiol. 2009;53(6):501-10.
Lonborg J, Vejlstrup N, Kelbaek H, Botker HE, Kim WY, Mathiasen AB, et al. Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction. Eur Heart J. 2012;33(12):1491-9.
Ussher JR, Drucker DJ. Cardiovascular actions of incretin-based therapies. Circ Res. 2014;114(11):1788- 803.
Basalay MV, Mastitskaya S, Mrochek A, Ackland GL, Del Arroyo AG, Sanchez J, et al. Glucagon-like peptide-1 (GLP-1) mediates cardioprotection by remote ischaemic conditioning. Cardiovasc Res. 2016;112(3):669-76.
Wright EJ, Hodson NW, Sherratt MJ, Kassem M, Lewis AL, Wallrapp C, et al. Combined MSC and GLP-1 Therapy Modulates Collagen Remodeling and Apoptosis following Myocardial Infarction. Stem Cells Int. 2016;2016:7357096.
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Details

Primary Language	English
Subjects	Health Care Administration
Journal Section	Research Articles
Authors	Özgür Tekin 0000-0003-3838-9990 Yiğit Uyanıkgil 0000-0002-4016-0522 Dilek Taşkıran 0000-0002-4505-0939
Publication Date	December 12, 2022
Submission Date	May 9, 2022
Published in Issue	Year 2022Volume: 61 Issue: 4

Cite

Vancouver	Tekin Ö, Uyanıkgil Y, Taşkıran D. Effect of glucagon-like peptide-1 on differentiation of adipose derived mesenchymal stem cells into cardiomyocytes. EJM. 2022;61(4):507-1.

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