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Article

Changes in mesenchymal stem cells following long-term culture in vitro

  • Authors:
    • Yajun Gu
    • Tao Li
    • Yanling Ding
    • Lingxian Sun
    • Tao Tu
    • Wei Zhu
    • Jiabo Hu
    • Xiaochun Sun
  • View Affiliations / Copyright

    Affiliations: The Blood Bank of Jiangyin, Wuxi, Jiangsu 214400, P.R. China, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
  • Pages: 5207-5215
    |
    Published online on: April 22, 2016
       https://doi.org/10.3892/mmr.2016.5169
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Abstract

Mesenchymal stem cells (MSCs), which can be isolated from umbilical cords and induced to differentiate into multiple cell types in vitro, represent an ideal source for cell and gene therapy. MSCs are typically expanded in culture prior to their therapeutic application. However, similar to other types of stem cell, MSCs undergo senescence following a certain number of cell expansion passages in vitro, and eventually stop proliferating. The objective of the present study was to measure the changes that occur over successive passages of MSCs during long‑term in vitro culture, and to detect the effect of aging on MSC morphology, phenotype, proliferation, cell cycle, differentiation, intracellular reactive oxygen species (ROS) levels and gene expression. To understand the importance of oxidative stress in the aging of adult stem cells, the current study established a cell model of H2O2‑induced MSC premature senescence. Analysis of the biological characteristics of human umbilical cord MSCs during replicative and premature senescence revealed the importance of extrinsic factors in the aging of stem cells, particularly ROS. The findings of the present study suggest that cellular senescence, a state of irreversible growth arrest, can be triggered by ROS. Thus, it is important to improve the extrinsic culture environment of MSCs to retain the phenotype of expanded cells and delay the process of senescence prior to their clinical application.
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1 

Forostyak S, Jendelova P and Sykova E: The role of mesenchymal stromal cells in spinal cord injury, regenerative medicine and possible clinical applications. Biochimie. 95:2257–2270. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Li T, Yan Y, Wang B, Qian H, Zhang X, Shen L, Wang M, Zhou Y, Zhu W, Li W and Xu W: Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis. Stem Cells Dev. 22:845–854. 2013. View Article : Google Scholar :

3 

Zhang Y, Cai W, Huang Q, Gu Y, Shi Y, Huang J, Zhao F, Liu Q, Wei X, Jin M, et al: Mesenchymal stem cells alleviate bacteria-induced liver injury in mice by inducing regulatory dendritic cells. Hepatology. 59:671–682. 2014. View Article : Google Scholar

4 

Woodbury D, Reynolds K and Black IB: Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis. J Neurosci Res. 69:908–917. 2002. View Article : Google Scholar : PubMed/NCBI

5 

Choudhery MS, Badowski M, Muise A and Harris DT: Comparison of human mesenchymal stem cells derived from adipose and cord tissue. Cytotherapy. 15:330–343. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Mamidi MK, Nathan KG, Singh G, Thrichelvam ST, Mohd Yusof NA, Fakharuzi NA, Zakaria Z, Bhonde R, Das AK and Majumdar AS: Comparative cellular and molecular analyses of pooled bone marrow multipotent mesenchymal stromal cells during continuous passaging and after successive cryopreser-vation. J Cell Biochem. 113:3153–3164. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Izadpanah R, Kaushal D, Kriedt C, Tsien F, Patel B, Dufour J and Bunnell BA: Long-term in vitro expansion alters the biology of adult mesenchymal stem cells. Cancer Res. 68:4229–4238. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Wagner W, Ho AD and Zenke M: Different facets of aging in human mesenchymal stem cells. Tissue Eng Part B Rev. 16:445–453. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Courtois-Cox S, Jones SL and Cichowski K: Many roads lead to oncogene-induced senescence. Oncogene. 27:2801–2809. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Chakkalakal JV, Jones KM, Basson MA and Brack AS: The aged niche disrupts muscle stem cell quiescence. Natrue. 490:355–360. 2012. View Article : Google Scholar

11 

Brandl A, Meyer M, Bechmann V, Nerlich M and Angele P: Oxidative stress induces senescence in human mesenchymal stem cells. Exp Cell Res. 317:1541–1547. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Chandler H and Peters G: Stressing the cell cycle in senescence and aging. Curr Opin Cell Biol. 25:765–771. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Kim YJ, Hwang SH, Lee SY, Shin KK, Cho HH, Bae YC and Jung JS: miR-486-5p induces replicative senescence of human adipose tissue-derived mesenchymal stem cells and its expression is controlled by high glucose. Stem Cells Dev. 21:1749–1760. 2012. View Article : Google Scholar

14 

Zhang DY, Wang HJ and Tan YZ: Wnt/β-catenin signaling induces the aging of mesenchymal stem cells through the DNA damage response and the p53/p21 pathway. PLoS One. 6:e213972011. View Article : Google Scholar

15 

Ho PJ, Yen ML, Tang BC, Chen CT and Yen BL: H2O2 accumulation mediates differentiation capacity alteration, but not proliferative decline, in senescent human fetal mesenchymal stem cells. Antioxid Redox Signal. 18:1895–1905. 2013. View Article : Google Scholar :

16 

Zhou BR, Xu Y, Wu D, Permatasari F, Gao YY and Luo D: Ginsenoside Rg1 protects human fibroblasts against psoralen- and UVA-induced premature senescence through a telomeric mechanism. Arch Dermatol Res. 304:223–228. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Thakur S, Sarkar B, Cholia RP, Gautam N, Dhiman M and Mantha AK: APE1/Ref-1 as an emerging therapeutic target for various human diseases: Phytochemical modulation of its functions. Exp Mol Med. 46:e1062014. View Article : Google Scholar : PubMed/NCBI

18 

Ju Z, Choudhury AR and Rudolph KL: A dual role of p21 in stem cell aging. Ann N Y Acad Sci. 100:333–344. 2007. View Article : Google Scholar

19 

Herbig U, Jobling WA, Chen BP, Chen DJ and Sedivy JM: Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). MOL CELL. 14:501–513. 2004. View Article : Google Scholar : PubMed/NCBI

20 

Collado M, Blasco MA and Serrano M: Cellular senescence in cancer and aging. Cell. 130:223–233. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Kawasaki H, Guan J and Tamama K: Hydrogen gas treatment prolongs replicative lifespan of bone marrow multipotential stromal cells in vitro while preserving differentiation and paracrine potentials. Biochem Biophys Res Commun. 397:608–613. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Hao H, Chen G, Liu J, Ti D, Zhao Y, Xu S, Fu X and Han W: Culturing on Wharton's jelly extract delays mesenchymal stem cell senescence through p53 and p16INK4a/pRb pathways. PLoS One. 8:e583142013. View Article : Google Scholar : PubMed/NCBI

23 

Lin TM, Tsai JL, Lin SD, Lai CS and Chang CC: Accelerated growth and prolonged lifespan of adipose tissue-derived human mesenchymal stem cells in a medium using reduced calcium and antioxidants. Stem Cells Dev. 14:92–102. 2005. View Article : Google Scholar : PubMed/NCBI

24 

Sharpless NE and DePinho RA: How stem cells age and why this makes us grow old. Nat Rev Mol Cell Biol. 8:703–713. 2007. View Article : Google Scholar : PubMed/NCBI

25 

Wang TT, Zeng GC, Li XC and Zeng HP: In vitro studies on the antioxidant and protective effect of 2-substituted -8-hydroxy-quinoline derivatives against H2O induced oxidative stress in BMSCs. Chem Biol Drugs Des. 75:214–222. 2010. View Article : Google Scholar

26 

Schellenberg A, Lin Q, Schuler H, Schüler H, Koch CM, Joussen S, Denecke B, Walenda G, Pallua N, Suschek CV, Zenke M and Wagner W: Replicative senescence of mesen-chymal stem cells causes DNA-methylation changes which correlate with repressive histone marks. Aging (Albany NY). 3:873–888. 2011. View Article : Google Scholar

27 

Zhang R, Poustovoitov MV, Ye X, Santos HA, Chen W, Daganzo SM, Erzberger JP, Serebriiskii IG, Canutescu AA, Dunbrack RL, et al: Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. Dev Cell. 8:19–30. 2005. View Article : Google Scholar

28 

Kim J, Kang JW, Park JH, Choi Y, Choi KS, Park KD, Baek DH, Seong SK, Min HK and Kim HS: Biological characterization of long-term cultured human mesenchymal stem cells. Arch Pharm Res. 32:117–126. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Li Z, Liu C, Xie Z, Song P, Zhao RC, Guo L, Liu Z and Wu Y: Epigenetic dysregulation in mesenchymal stem cell aging and spontaneous differentiation. Plos One. 6:e205262011. View Article : Google Scholar : PubMed/NCBI

30 

Wagner W, Horn P, Castoldi M, Diehlmann A, Bork S, Saffrich R, Benes V, Blake J, Pfister S, Eckstein V and Ho AD: Replicative senescence of mesenchymal stem cells: a continuous and organized process. PLoS One. 3:e22132008. View Article : Google Scholar : PubMed/NCBI

31 

Moerman EJ, Teng K, Lipschitz DA and Lecka-Czernik B: Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: The role of PPAR-gamma2 transcription factor and TGF-beta/BMP signaling pathways. Aging Cell. 3:379–389. 2004. View Article : Google Scholar : PubMed/NCBI

32 

Edwards M, Rassin DK, Izumi T, Mitra S and Perez-Polo JR: APE/Ref-1 responses to oxidative stress in aged rats. J Neurosci Res. 54:635–638. 1998. View Article : Google Scholar : PubMed/NCBI

33 

Tanaka T, Halicka HD, Huang X, Traganos F and Darzynkiewicz Z: Constitutive histone H2AX phosphory-lation and ATM activation, the reporters of DNA damage by endogenous oxidants. Cell Cycle. 5:1940–1945. 2006. View Article : Google Scholar : PubMed/NCBI

34 

Wagner W, Horn P, Bork S and Ho AD: Aging of hematopoietic stem cells is regulated by the stem cell niche. Exp Gerontol. 43:974–980. 2008. View Article : Google Scholar : PubMed/NCBI

35 

Yagi H, Tan J and Tuan RS: Polyphenols suppress hydrogen peroxide-induced oxidative stress in human bone-marrow derived mesenchymal stem cells. J Cell Biochem. 114:1163–1173. 2013. View Article : Google Scholar

36 

Seo SK, Yang W, Park YM, Lee WT, Park KA and Lee JE: Overexpression of human arginine decarboxylase rescues human mesenchymal stem cells against H O cell survival protein activation. J Korean Med Sci. 28:366–373. 2013. View Article : Google Scholar : PubMed/NCBI

37 

Wang FW, Wang Z, Zhang YM, Du ZX, Zhang XL, Liu Q, Guo YJ, Li XG and Hao AJ: Protective effect of melatonin on bone marrow mesenchymal stem cells against hydrogen peroxide-induced apoptosis in vitro. J Cell Biochem. 114:2346–2355. 2013. View Article : Google Scholar : PubMed/NCBI

38 

Fritz G, Grösch S, Tomicic M and Kaina B: APE/Ref-1 and the mammalian response to genotoxic stress. Toxicology. 193:67–78. 2003. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Gu Y, Li T, Ding Y, Sun L, Tu T, Zhu W, Hu J and Sun X: Changes in mesenchymal stem cells following long-term culture in vitro. Mol Med Rep 13: 5207-5215, 2016.
APA
Gu, Y., Li, T., Ding, Y., Sun, L., Tu, T., Zhu, W. ... Sun, X. (2016). Changes in mesenchymal stem cells following long-term culture in vitro. Molecular Medicine Reports, 13, 5207-5215. https://doi.org/10.3892/mmr.2016.5169
MLA
Gu, Y., Li, T., Ding, Y., Sun, L., Tu, T., Zhu, W., Hu, J., Sun, X."Changes in mesenchymal stem cells following long-term culture in vitro". Molecular Medicine Reports 13.6 (2016): 5207-5215.
Chicago
Gu, Y., Li, T., Ding, Y., Sun, L., Tu, T., Zhu, W., Hu, J., Sun, X."Changes in mesenchymal stem cells following long-term culture in vitro". Molecular Medicine Reports 13, no. 6 (2016): 5207-5215. https://doi.org/10.3892/mmr.2016.5169
Copy and paste a formatted citation
x
Spandidos Publications style
Gu Y, Li T, Ding Y, Sun L, Tu T, Zhu W, Hu J and Sun X: Changes in mesenchymal stem cells following long-term culture in vitro. Mol Med Rep 13: 5207-5215, 2016.
APA
Gu, Y., Li, T., Ding, Y., Sun, L., Tu, T., Zhu, W. ... Sun, X. (2016). Changes in mesenchymal stem cells following long-term culture in vitro. Molecular Medicine Reports, 13, 5207-5215. https://doi.org/10.3892/mmr.2016.5169
MLA
Gu, Y., Li, T., Ding, Y., Sun, L., Tu, T., Zhu, W., Hu, J., Sun, X."Changes in mesenchymal stem cells following long-term culture in vitro". Molecular Medicine Reports 13.6 (2016): 5207-5215.
Chicago
Gu, Y., Li, T., Ding, Y., Sun, L., Tu, T., Zhu, W., Hu, J., Sun, X."Changes in mesenchymal stem cells following long-term culture in vitro". Molecular Medicine Reports 13, no. 6 (2016): 5207-5215. https://doi.org/10.3892/mmr.2016.5169
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