AI Chat Paper
Discover the SciOpen Platform and Achieve Your Research Goals with Ease.
Human umbilical cord mesenchymal stem cells (HUC-MSCs) are pluripotent and functional in many biological processes, by which releasing secretary factors to promote the self-repairing of damaged tissue or developing into functional cell at local organ. However, there is a high risk that oxidative stress would reduce the pluripotency and factor-secretion during the preparation and transplantation. Therefore, reducing oxidative stress is expected to improve the efficacy of HUC-MSCs therapy. Zinc (Zn) is an essential trace element which involves in the resistance of oxidative stress. To investigate Zn-regulated signaling pathways, we have profiled the gene expression at transcriptome level in primary HUC-MSCs treated with zinc sulfate, followed with GO and KEGG gene enrichment analysis. Zn treatment improved signal pathways for mineral absorption, cell growth, and cell death. Zn deficiency was mimicked by TPEN administration, which suppressed cell proliferation and reduced the expression of HUC-MSCs surface stem cell markers CD73, CD90 and CD105 by flow cytometry. Nuclear factor erythrocyte 2 related factor 2 (Nrf2) plays an important role in antioxidant biological processes. In vitro treatment of Zn significantly increased Nrf2 and Sirt3 expression at gene level and protein level respectively. Zn supplementation inhibited TPEN-induced failure of cell survival and reversed the reduction of Nrf2 and Sirt3 expression, which further reduced the production of ROS. Zn successfully presented its anti-oxidation effect by activating Nrf2/Sirt3 signaling pathway in HUC-MSCs. Zn supplementation may improve the efficacy of HUC-MSCs therapy with reduced oxidative stress.
Afshar Ebrahimi F, Foroozanfard F, Aghadavod E, Bahmani F, Asemi Z (2018) The effects of magnesium and zinc co-supplementation on biomarkers of inflammation and oxidative stress, and gene expression related to inflammation in polycystic ovary syndrome: a randomized controlled clinical trial. Biol Trace Elem Res 184(2): 300−307
Benameur L, Charif N, Li Y, Stoltz JF, de Isla N (2015) Toward an understanding of mechanism of aging-induced oxidative stress in human mesenchymal stem cells. Biomed Mater Eng 25(1 Suppl): 41−46
Camilletti MA, Martinez Mayer J, Vishnopolska SA, Perez-Millan MI (2020) From pituitary stem cell differentiation to regenerative medicine. Front Endocrinol (Lausanne) 11: 614999. https://doi.org/10.3389/fendo.2020.614999
Ding DC, Chang YH, Shyu WC, Lin SZ (2015) Human umbilical cord mesenchymal stem cells: a new era for stem cell therapy. Cell Transplant 24(3): 339−347
Farruggia C, Kim MB, Bae M, Lee Y, Pham TX, Yang Y, Han MJ, Park YK, Lee JY (2018) Astaxanthin exerts anti-inflammatory and antioxidant effects in macrophages in NRF2-dependent and independent manners. J Nutr Biochem 62: 202−209
Gammoh NZ, Rink L (2017) Zinc in Infection and Inflammation. Nutrients 9(6): 624. https://doi.org/10.3390/nu9060624
Hadj Abdallah N, Baulies A, Bouhlel A, Bejaoui M, Zaouali MA, Ben Mimouna S, Messaoudi I, Fernandez-Checa JC, Garcia Ruiz C, Ben Abdennebi H (2018) Zinc mitigates renal ischemia-reperfusion injury in rats by modulating oxidative stress, endoplasmic reticulum stress, and autophagy. J Cell Physiol 233(11): 8677−8690
Hirschey MD, Shimazu T, Goetzman E, Jing E, Schwer B, Lombard DB, Grueter CA, Harris C, Biddinger S, Ilkayeva OR, Stevens RD, Li Y, Saha AK, Ruderman NB, Bain JR, Newgard CB, Farese RV, J r., Alt FW, Kahn CR, Verdin E (2010) SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature 464(7285): 121−125
Hubber EL, Rackham CL, Jones PM (2021) Protecting islet functional viability using mesenchymal stromal cells. Stem Cells Transl Med
Katwal G, Baral D, Fan X, Weiyang H, Zhang X, Ling L, Xiong Y, Ye Q, Wang Y (2018) SIRT3 a major player in attenuation of hepatic ischemia-reperfusion injury by reducing ROS via its downstream mediators: SOD2, CYP-D, and HIF-1alpha. Oxid Med Cell Longev 2018: 2976957. https://doi.org/10.1155/2018/2976957
Kumar A, Dhaliwal N, Dhaliwal J, Dharavath RN, Chopra K (2020) Astaxanthin attenuates oxidative stress and inflammatory responses in complete Freund-adjuvant-induced arthritis in rats. Pharmacol Rep 72(1): 104−114
Li J, Yao Z, Xiong H, Cui H, Wang X, Zheng W, Qian Y, Fan C (2020) Extracellular vesicles from hydroxycamptothecin primed umbilical cord stem cells enhance anti-adhesion potential for treatment of tendon injury. Stem Cell Res Ther 11(1): 500. https://doi.org/10.1186/s13287-020-02016-8
Li X, Michaeloudes C, Zhang Y, Wiegman CH, Adcock IM, Lian Q, Mak JCW, Bhavsar PK, Chung KF (2018) Mesenchymal stem cells alleviate oxidative stress-induced mitochondrial dysfunction in the airways. J Allergy Clin Immunol 141(5): 1634−1645
Liu J, Li D, Zhang T, Tong Q, Ye RD, Lin L (2017) SIRT3 protects hepatocytes from oxidative injury by enhancing ROS scavenging and mitochondrial integrity. Cell Death Dis 8(10): e3158. https://doi.org/10.1038/cddis.2017.564
Lu X, Zhang Q, Xu L, Lin X, Fu J, Wang X, Liu Y, Lin Y, Li B, Wang R, Liu L, Mi X, Wei H, Tan Y, Fang Y (2020) Zinc is essential for the transcription function of the PGC-1alpha/Nrf2 signaling pathway in human primary endometrial stromal cells. Am J Physiol Cell Physiol 318(3): C640−C648
Ma K, Zhu B, Wang Z, Cai P, He M, Ye D, Yan G, Zheng L, Yang L, Zhao J (2020) Articular chondrocyte-derived extracellular vesicles promote cartilage differentiation of human umbilical cord mesenchymal stem cells by activation of autophagy. J Nanobiotechnology 18(1): 163. https://doi.org/10.1186/s12951-020-00708-0
Marchev AS, Dimitrova PA, Burns AJ, Kostov RV, Dinkova-Kostova AT, Georgiev MI (2017) Oxidative stress and chronic inflammation in osteoarthritis: can NRF2 counteract these partners in crime? Ann N Y Acad Sci 1401(1): 114−135
Millward DJ (2017) Nutrition, infection and stunting: the roles of deficiencies of individual nutrients and foods, and of inflammation, as determinants of reduced linear growth of children. Nutr Res Rev 30(1): 50−72
Oggu GS, Sasikumar S, Reddy N, Ella KKR, Rao CM, Bokara KK (2017) Gene delivery approaches for mesenchymal stem cell therapy: strategies to increase efficiency and specificity. Stem Cell Rev Rep 13(6): 725−740
Oh JY, Choi GE, Lee HJ, Jung YH, Chae CW, Kim JS, Lee CK, Han HJ (2019) 17beta-estradiol protects mesenchymal stem cells against high glucose-induced mitochondrial oxidants production via Nrf2/Sirt3/MnSOD signaling. Free Radic Biol Med 130: 328−342
Ohashi W, Fukada T (2019) Contribution of zinc and zinc transporters in the pathogenesis of inflammatory bowel diseases. J Immunol Res 2019: 8396878. https://doi.org/10.1155/2019/8396878
Park SJ, Kwon W, Park S, Jeong J, Kim D, Jang S, Kim SY, Sung Y, Kim MO, Choi SK, Ryoo ZY (2021) Jazf1 acts as a regulator of insulin-producing beta-cell differentiation in induced pluripotent stem cells and glucose homeostasis in mice. FEBS J . https://doi.org/10.1111/febs.15751
Rosenkilde MM, Schwartz TW (2004) The chemokine system — a major regulator of angiogenesis in health and disease. APMIS 112(7-8): 481−495
Roura S, Vives J (2019) Extracellular vesicles: squeezing every drop of regenerative potential of umbilical cord blood. Metabolism 95: 102−104
Sanna A, Firinu D, Zavattari P, Valera P (2018) Zinc status and autoimmunity: a systematic review and meta-analysis. Nutrients 10(1): 68. https://doi.org/10.3390/nu10010068
Song IH, Jung KJ, Lee TJ, Kim JY, Sung EG, Bae YC, Park YH (2018) Mesenchymal stem cells attenuate adriamycin-induced nephropathy by diminishing oxidative stress and inflammation via downregulation of the NF-kB. Nephrology (Carlton) 23(5): 483−492
Su WH, Wang CJ, Fu HC, Sheng CM, Tsai CC, Cheng JH, Chuang PC (2019) Human umbilical cord mesenchymal stem cells extricate bupivacaine-impaired skeletal muscle function via mitigating neutrophil-mediated acute inflammation and protecting against fibrosis. Int J Mol Sci 20(17): 4312. https://doi.org/10.3390/ijms20174312
Vohra M, Sharma A, Bagga R, Arora SK (2020) Human umbilical cord-derived mesenchymal stem cells induce tissue repair and regeneration in collagen-induced arthritis in rats. J Clin Transl Res 6(6): 203−216
Wang S, Nie P, Lu X, Li C, Dong X, Yang F, Luo P, Li B (2020a) Nrf2 participates in the anti-apoptotic role of zinc in Type 2 diabetic nephropathy through Wnt/beta-catenin signaling pathway. J Nutr Biochem 84: 108451. https://doi.org/10.1016/j.jnutbio.2020.108451
Wang S, Zhang C, Niyazi S, Zheng L, Li J, Zhang W, Xu M, Rong R, Yang C, Zhu T (2017) A novel cytoprotective peptide protects mesenchymal stem cells against mitochondrial dysfunction and apoptosis induced by starvation via Nrf2/Sirt3/FoxO3a pathway. J Transl Med 15(1): 33. https://doi.org/10.1186/s12967-017-1144-5
Wang W, Ji Z, Yuan C, Yang Y (2020b) Mechanism of human umbilical cord mesenchymal stem cells derived-extracellular vesicle in cerebral ischemia-reperfusion injury. Neurochem Res 46(3): 455−467
Yang C, Wu M, You M, Chen Y, Luo M, Chen Q (2021) The therapeutic applications of mesenchymal stromal cells from human perinatal tissues in autoimmune diseases. Stem Cell Res Ther 12(1): 103. https://doi.org/10.1186/s13287-021-02158-3
Yao J, Zheng J, Cai J, Zeng K, Zhou C, Zhang J, Li S, Li H, Chen L, He L, Chen H, Fu H, Zhang Q, Chen G, Yang Y, Zhang Y (2019) Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia-reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response. FASEB J 33(2): 1695−1710
Ziaei M, Zhang J, Patel DV, McGhee CNJ (2017) Umbilical cord stem cells in the treatment of corneal disease. Surv Ophthalmol 62(6): 803−815
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
