Research progresses in aging mechanisms of mesenchymal stem cells

doi:10.3877/cma.j.issn.2095-1221.2017.04.010

Abstract

Abstract:

Mesenchymal stem cells (MSCs) with self-renewal and multipotential differentiation are thought to be the ideal seed cell in the repair and regeneration of orthopedic injury and degenerative disease. However, the same as any other somatic cells, MSCs are also aging upon a long-term culture which will have a negative effect in the treatment of disease. Thus it is important to understand the mechanisms of aging and look for the solution to delay or reverse the aging of MSCs. This review discuss the aging mechanisms of MSCs mainly from the telomeres and telomerase system, oxidative stress, silent information regulator protein, high glucose, Wnt/β-catenin signaling pathways activation, DNA damage and so on. We look forward to finding the solution to achieve the goal of delaying or reversing the aging process of MSCs.

Key words: Mesenchymal stem cells, Aging, Silent information regulator protein, Anti-aging

Yang Liu, Xinmin Feng, Tao Chen, Zenan Huang, Liang Zhang. Research progresses in aging mechanisms of mesenchymal stem cells[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2017, 07(04): 242-246.

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https://zhxbygxbzz.cma-cmc.com.cn/EN/Y2017/V07/I04/242

References 58

[1]	Elabd C, Centeno CJ, Schultz JR, et al. Intra-discal injection of autologous, hypoxic cultured bone marrow-derived mesenchymal stem cells in five patients with chronic lower back pain: a long-term safety and feasibility study[J]. J Transl Med, 2016, 14:253.
[2]	Pereira CL, Gonçalves RM, Peroglio M, et al. The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the recruitment of MSCs in degenerating intervertebral discs[J]. Biomaterials, 2014, 35(28):8144-8153.
[3]	Hayflick L. The limited in vitro lifetime of human diploid cell strains[J]. Exp Cell Res, 1965, 37:614-636.
[4]	Oh J, Lee YD, Wagers AJ. Stem cell aging:mechanisms,regulators and therapeutic opportunities[J]. Nat Med, 2014, 20(8):870-880.
[5]	Benameur L, Charif N, Li YE, et al. Toward an understanding of mechanism of aging-induced oxidative stress in human mesenchymal stem cells[J]. Biomed Mater Eng, 2015, 25(1):S41-S46.
[6]	Trachana V, Petrakis S, Fotiadis Z, et al. Human mesenchymal stem cells with enhanced telomerase activity acquire resistance against oxidative stress-induced genomic damage[J]. Cytotherapy, 2017, pii: S1465-3249(17)30541-30548. [Epub ahead of print]
[7]	Carrillo J, Calvete O, Pintado-Berninches L, et al. Mutations in XLF/NHEJ1/cernunnos gene results in downregulation of telomerase genes expression and telomere shortening[J]. Hum Mol Genet, 2017, 26(10):1900-1914.
[8]	He L, Zheng Y, Wan Y, et al. A shorter telomere is the key factor in preventing cultured human mesenchymal stem cells from senescence escape[J]. Histochem Cell Biol, 2014, 142(3):257-267.
[9]	Wang X, Zou X, Zhao J, et al. Site-specific characteristics of bone marrow mesenchymal stromal cells modify the effect of aging on the skeleton [J]. Rejuvenation Res, 2015, [Epub ahead of print]
[10]	Zhao Q, Wang XY, Yu XX, et al. Expression of human telomerase reverse transcriptase mediates the senescence of mesenchymal stem cells through the PI3K/AKT signaling pathway[J]. Int J Mol Med, 2015, 36(3):857-864.
[11]	Choo KB, Tai L, Hymavathee KS, et al. Oxidative stress-induced premature senescence in Wharton's jelly-derived mesenchymal stem cells[J]. Int J Med Sci, 2014, 11(11):1201-1207.
[12]	Lee JH, Jung HK, Han YS, et al. Antioxidant effects of Cirsium setidens extract on oxidative stress in human mesenchymal stem cells[J]. Mol Med Rep, 2016, 14(4):3777-3784.
[13]	Jeong SG, Cho GW. Endogenous ROS levels are increased in replicative senescence in human bone marrow mesenchymal stromal cells[J]. Biochem Biophys Res Commun, 2015, 460(4):971-976.
[14]	Stolzing A, Jones E, Mcgonagle D, et al. Age-related changes in human bone marrow-derived mesenchymal stem cells: Consequences for cell therapies[J]. Mech Ageing Dev, 2008, 129(3):163-173.
[15]	Lee JS, Lee MO, Moon BH, et al. Senescent growth arrest in mesenchymal stem cells is bypassed by Wip1-Mediated downregulation of intrinsic stress signaling pathways[J]. Stem Cells, 2009, 27(8):1963-1975.
[16]	Ko E, Lee KY, Hwang DS. Human umbilical cord Blood-Derived mesenchymal stem cells undergo cellular senescence in response to oxidative stress[J]. Stem Cells Dev, 2012, 21(11):1877-1886.
[17]	Borodkina A, Shatrova A, Abushik PA, et al. Interaction between ROS dependent DNA damage, mitochondria and p38 MAPK underlies senescence of human adult stem cells[J]. Aging, 2014, 6(6):481-495.
[18]	Zhou L, Chen X, Liu T, et al. Melatonin reverses H₂O₂-induced premature senescence in mesenchymal stem cells via the SIRT1-dependent pathway[J]. J Pineal Res, 2015, 59(2):190-205.
[19]	Larsen SA, Kassem M, Rattan SI. Glucose metabolite glyoxal induces senescence in telomerase-immortalized human mesenchymal stem cells[J]. Chem Cent J, 2012, 6(1):18.
[20]	Kitada M, Kume S, Takeda-Watanabe A, et al. Sirtuins and renal diseases: relationship with aging and diabetic nephropathy[J]. Clin Sci (Lond), 2013, 124(3):153-164.
[21]	Li Y, He X, Li Y, et al. Nicotinamide phosphoribosyltransferase(Nampt)affects the lineage fate determination of mesenchymal stem cells:a possible cause for reduced osteogenesis and increased adipogenesis in older individuals[J]. J Bone Miner Res, 2011, 26(11):2656-2664.
[22]	Chen H, Liu X, Chen H, et al. Role of SIRT1 and AMPK in mesenchymal stem cells differentiation [J]. Ageing Res Rev, 2014, 13:55-64.
[23]	Simic P, Zainabadi K, Bell E, et al. SIRT1 regulates differentiation of mesenchymal stem cells by deacetylating β-catenin[J]. EMBO Mol Med, 2013, 5(3):430-440.
[24]	Kim YJ, Hwang SH, Lee SY, et al. miR-486-5p induces replicative senescence of human adipose tissue-derived mesenchymal stem cells and its expression is controlled by high glucose[J]. Stem Cells Dev, 2012, 21(10):1749-1760.
[25]	Wang XX, Ma SS, Meng N, et al. Resveratrol exerts Dosage-Dependent effects on the Self-Renewal and neural differentiation of hUC-MSCs[J]. Mol Cells, 2016, 39(5):418-425.
[26]	Ma C, Pi CC, Yang YE, et al. Nampt expression decreases Age-Related senescence in rat bone marrow mesenchymal stem cells by targeting Sirt1[J]. PLoS One, 2017, 12(1):e0170930.
[27]	Son MJ, Kwon Y, Son T, et al. Restoration of mitochondrial NAD(+)levels delays stem cell senescence and facilitates reprogramming of aged somatic cells[J]. Stem Cells, 2016, 34(12): 2840-2851.
[28]	Wang XQ, Shao Y, Ma CY, et al. Decreased SIRT3 in aged human mesenchymal stromal/stem cells increases cellular susceptibility to oxidative stress[J]. J Cell Mol Med, 2014, 18(11):2298-2310.
[29]	Sun HL, Wu YR, Fu DJ, et al. SIRT6 regulates osteogenic differentiation of rat bone marrow mesenchymal stem cells partially via suppressing the nuclear factor-kappa B signaling pathway[J]. Stem Cells, 2014, 32(7):1943-1955.
[30]	Mostoslavsky R, Chua KF, Lombard DB, et al. Genomic instability and aging-like phenotype in the absence of mammalian SIRT6[J]. Cel, 2006, 124(2):315-329.
[31]	Gertler AA, Cohen HY. SIRT6, a protein with many faces[J]. Biogerontology, 2013, 14(6):629-639.
[32]	Lee N, Kim DK, Kim ES, et al. Comparative interactomes of SIRT6 and SIRT7:Implication of functional links to aging[J]. Proteomics, 2014, 14(13/14):1610-1622.
[33]	Zhang B, Liu N, Gu B, et al. [Observing the effect of high glucose on proliferation of bone marrow stromal stem cells through Wnt/Β-catenin pathway][J]. Zhongguo yi xue ke xue yuan xue bao, 2014, 36(4):389-393.
[34]	Lei LT, Chen JB, Zhao YL, et al. Resveratrol attenuates senescence of adipose-derived mesenchymal stem cells and restores their paracrine effects on promoting insulin secretion of INS-1 cells through Pim-1[J]. Eur Rev Med Pharmacol Sci, 2016, 20(6):1203-1213.
[35]	孙超，王言，邢辉, 等. 葡萄糖及O-GlcNAc糖基化对人骨髓间充质干细胞增殖、凋亡、衰老的影响[J]. 中国脊柱脊髓杂志, 2016, 26(4):354-361.
[36]	Clevers H, Nusse R. Wnt/β-Catenin signaling and disease[J]. Cell, 2012, 149(6):1192-1205.
[37]	Zhang DY, Pan Y, Zhang C, et al. Wnt/beta-catenin signaling induces the aging of mesenchymal stem cells through promoting the ROS production[J]. Mol Cell Biochem, 2013, 374(1/2):13-20.
[38]	Kajla S, Mondol AS, Nagasawa A, et al. A crucial role for Nox 1 in redox-dependent regulation of Wnt-beta-catenin signaling[J]. FASEB Journal, 2012, 26(5):2049-2059.
[39]	Gu Z, Tan W, Feng G, et al. Wnt/β-catenin signaling mediates the senescence of bone marrow-mesenchymal stem cells from systemic lupus erythematosus patients through the p53/p21 pathway[J]. Mol Cell Biochem, 2014, 387(1/2):27-37.
[40]	Zhang DY, Wang HJ, Tan YZ. Wnt/beta-catenin signaling induces the aging of mesenchymal stem cells through the DNA damage response and the p53/p21 Pathway[J]. PLoS One, 2011, 6(6):e21397.
[41]	Tichon A, Eitan E, Kurkalli BG, et al. Oxidative stress protection by novel telomerase activators in mesenchymal stem cells derived from healthy and diseased individuals[J]. Curr Mol Med, 2013, 13(6):1010-1022.
[42]	Yahata T, Takanashi T, Muguruma Y, et al. Accumulation of oxidative DNA damage restricts the self-renewal capacity of human hematopoietic stem cells[J]. Blood, 2011, 118(11):2941-2950.
[43]	Alves H, Munoz-Najar U, De Wit J, et al. A Link between the accumulation of DNA damage and loss of multi-potency of human mesenchymal stromal cells[J]. J Cell Mol Med, 2010, 14(12):2729-2738.
[44]	Minieri V, Saviozzi S, Gambarotta G, et al. Persistent DNA damage-induced premature senescence alters the functional features of human bone marrow mesenchymal stem cells[J]. J Cell Mol Med, 2015, 19(4):734-743.
[45]	Yu QJ, Katlinskaya YV, Carbone CJ, et al. DNA-Damage-Induced type I interferon promotes senescence and inhibits stem cell function[J]. Cell Rep, 2015, 11(5):785-797.
[46]	Shearier E, Xing Q, Qian ZC, et al. Physiologically low Oxygen enhances biomolecule production and stemness of mesenchymal stem cell spheroids[J]. Tissue Eng Part C Methods, 2016, 22(4):360-369.
[47]	Fehrer C, Brunauer R, Laschober GA, et al. Reduced Oxygen tension attenuates differentiation capacity of human mesenchymal stem cells and prolongs their lifespan[J]. Aging Cell, 2007, 6(6):745-757.
[48]	Kanehira M, Kikuchi T, Ohkouchi SA, et al. Targeting lysophosphatidic acid signaling retards Culture-Associated senescence of human marrow stromal cells[J]. PLoS One, 2012, 7(2):e32185.
[49]	Jung JW, Lee S, Seo MS, et al. Histone deacetylase controls adult stem cell aging by balancing the expression of polycomb genes and jumonji domain containing 3[J]. Cellular and Molecular Life Sciences, 2010, 67(7):1165-1176.
[50]	郑晨曦，隋秉东，胡成虎, 等. 维生素C增强衰老个体来源的骨髓间充质干细胞的增殖能力[J]. 南方医科大学学报, 2015, 35(12):1689-1693.
[51]	Gharibi B, Hughes FJ. Effects of medium supplements on proliferation, differentiation potential, and in vitro expansion of mesenchymal stem cells[J]. Stem Cells Transl Med, 2012, 1(11):771-782.
[52]	Mohammadi S, Nikbakht M, Malek MA, et al. Human platelet lysate as a Xeno free alternative of fetal bovine serum for the in vitro expansion of human mesenchymal stromal cells[J]. Int J Hematol Oncol Stem Cell Res, 2016, 10(3):161-171.
[53]	詹菲，徐志伟，黄进, 等. 左归丸对衰老大鼠骨髓间充质干细胞增殖的影响[J]. 中华中医药杂志, 2015, 30(7):2518-2521.
[54]	Sabapathy V, Kumar S. hiPSC-derived iMSCs: NextGen MSCs as an advanced therapeutically active cell resource for regenerative medicine[J]. J Cell Mol Med, 2016, 20(8):1571-1588.
[55]	Sequiera GL, Saravanan S, Dhingra S. Human-induced pluripotent stem cell-derived mesenchymal stem cells as an individual-specific and renewable source of adult stem cells [J]. Methods Mol Biol, 2017, 1553:183-190.
[56]	Lian QZ, Zhang YE, Zhang JQ, et al. Functional mesenchymal stem cells derived from human induced pluripotent stem cells attenuate limb ischemia in mice[J]. Circulation, 2010, 121(9):1113-1123.
[57]	Wei H, Tan G, Manasi, et al. One-step derivation of cardiomyocytes and mesenchymal stem cells from human pluripotent stem cells[J]. Stem Cell Res, 2012, 9(2):87-100.
[58]	Frobel J, Hemeda H, Lenz M, et al. Epigenetic rejuvenation of mesenchymal stromal cells derived from induced pluripotent stem cells[J]. Stem Cell Reports, 2014, 3(3):414-422.

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