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Stem Cells and DNA Repair Capacity: Muse Stem Cells Are Among the Best Performers

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Book cover Muse Cells

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1103))

Abstract

Stem cells persist for long periods in the body and experience many intrinsic and extrinsic stresses. For this reason, they present a powerful and effective DNA repair system in order to properly fix DNA damage and avoid the onset of a degenerative process, such as neoplastic transformation or aging. In this chapter, we compare the DNA repair ability of pluripotent stem cells (ESCs, iPSCs, and Muse cells) and other adult stem cells. We also describe personal investigations showing a robust and effective capacity of Muse cells in sensing and repairing DNA following chemical and physical stress. Muse cells can repair DNA through base and nucleotide excision repair mechanisms, BER and NER, respectively. Furthermore, they present a pronounced capacity in repairing double-strand breaks by the nonhomologous end joining (NHEJ) process. The studies addressing the role of DNA damage repair in the biology of stem cells are of paramount importance for comprehension of their functions and, also, for setting up effective and safe stem cell-based therapy.

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References

  1. Tower J (2012) Stress and stem cells. Wiley Interdiscip Rev Dev Biol 1(6):789–802

    Article  CAS  Google Scholar 

  2. Richardson C, Yan S, Vestal CG (2015) Oxidative stress, bone marrow failure, and genome instability in hematopoietic stem cells. Int J Mol Sci 16(2):2366–2385

    Article  CAS  Google Scholar 

  3. Ruzankina Y, Asare A, Brown EJ (2008) Replicative stress, stem cells and aging. Mech Ageing Dev 129(7–8):460–466

    Article  CAS  Google Scholar 

  4. Chakarov S et al (2014) DNA damage and mutation. Types of DNA damage. Biodiscovery 11:1–10

    Google Scholar 

  5. Branzei D, Foiani M (2008) Regulation of DNA repair throughout the cell cycle. Nat Rev Mol Cell Biol 9(4):297–308

    Article  CAS  Google Scholar 

  6. Dexheimer TS (2013) DNA repair pathways and mechanisms. In: Mathews LA, Cabarcas SM, Hurt E (eds) DNA repair of cancer stem cells. Springer, New York, pp 19–32

    Chapter  Google Scholar 

  7. Alessio N et al (2016) Mesenchymal stromal cells having inactivated RB1 survive following low irradiation and accumulate damaged DNA: Hints for side effects following radiotherapy. Cell Cycle 16(3):251–258

    Article  Google Scholar 

  8. Zanichelli F et al (2012) Dose-dependent effects of R-sulforaphane isothiocyanate on the biology of human mesenchymal stem cells, at dietary amounts, it promotes cell proliferation and reduces senescence and apoptosis, while at anti-cancer drug doses, it has a cytotoxic effect. Age (Dordr) 34(2):281–293

    Article  CAS  Google Scholar 

  9. Ilic D, Ogilvie C (2017) Concise review: human embryonic stem cells-what have we done? What are we doing? Where are we going? Stem Cells 35(1):17–25

    Article  CAS  Google Scholar 

  10. Hong Y et al (2007) Protecting genomic integrity in somatic cells and embryonic stem cells. Mutat Res 614(1–2):48–55

    Article  CAS  Google Scholar 

  11. Lin Q, Donahue SL, Ruley HE (2006) Genome maintenance and mutagenesis in embryonic stem cells. Cell Cycle 5(23):2710–2714

    Article  CAS  Google Scholar 

  12. Tichy ED, Stambrook PJ (2008) DNA repair in murine embryonic stem cells and differentiated cells. Exp Cell Res 314(9):1929–1936

    Article  CAS  Google Scholar 

  13. Maynard S et al (2008) Human embryonic stem cells have enhanced repair of multiple forms of DNA damage. Stem Cells 26(9):2266–2274

    Article  Google Scholar 

  14. Savatier P et al (2002) Analysis of the cell cycle in mouse embryonic stem cells. Methods Mol Biol 185:27–33

    CAS  PubMed  Google Scholar 

  15. Adams BR et al (2010) Dynamic dependence on ATR and ATM for double-strand break repair in human embryonic stem cells and neural descendants. PLoS One 5(4):e10001

    Article  Google Scholar 

  16. Francis R, Richardson C (2007) Multipotent hematopoietic cells susceptible to alternative double-strand break repair pathways that promote genome rearrangements. Genes Dev 21(9):1064–1074

    Article  CAS  Google Scholar 

  17. Adams BR et al (2010) ATM-independent, high-fidelity nonhomologous end joining predominates in human embryonic stem cells. Aging (Albany NY) 2(9):582–596

    Article  CAS  Google Scholar 

  18. Bogomazova AN et al (2011) Error-prone nonhomologous end joining repair operates in human pluripotent stem cells during late G2. Aging (Albany NY) 3(6):584–596

    Article  Google Scholar 

  19. Lengner CJ (2010) iPS cell technology in regenerative medicine. Ann N Y Acad Sci 1192:38–44

    Article  CAS  Google Scholar 

  20. Yamanaka S, Blau HM (2010) Nuclear reprogramming to a pluripotent state by three approaches. Nature 465(7299):704–712

    Article  CAS  Google Scholar 

  21. Fan J et al (2011) Human induced pluripotent cells resemble embryonic stem cells demonstrating enhanced levels of DNA repair and efficacy of nonhomologous end-joining. Mutat Res 713(1–2):8–17

    Article  CAS  Google Scholar 

  22. Bracker TU et al (2006) Stringent regulation of DNA repair during human hematopoietic differentiation: a gene expression and functional analysis. Stem Cells 24(3):722–730

    Article  CAS  Google Scholar 

  23. Hsu PH, Hanawalt PC, Nouspikel T (2007) Nucleotide excision repair phenotype of human acute myeloid leukemia cell lines at various stages of differentiation. Mutat Res 614(1–2):3–15

    Article  CAS  Google Scholar 

  24. Casorelli I et al (2007) Methylation damage response in hematopoietic progenitor cells. DNA Repair (Amst) 6(8):1170–1178

    Article  CAS  Google Scholar 

  25. Nijnik A et al (2007) DNA repair is limiting for haematopoietic stem cells during ageing. Nature 447(7145):686–690

    Article  CAS  Google Scholar 

  26. Hildrestrand GA et al (2007) The capacity to remove 8-oxoG is enhanced in newborn neural stem/progenitor cells and decreases in juvenile mice and upon cell differentiation. DNA Repair (Amst) 6(6):723–732

    Article  CAS  Google Scholar 

  27. Nouspikel T, Hanawalt PC (2000) Terminally differentiated human neurons repair transcribed genes but display attenuated global DNA repair and modulation of repair gene expression. Mol Cell Biol 20(5):1562–1570

    Article  CAS  Google Scholar 

  28. Nowak E et al (2006) Radiation-induced H2AX phosphorylation and neural precursor apoptosis in the developing brain of mice. Radiat Res 165(2):155–164

    Article  CAS  Google Scholar 

  29. Galderisi U, Giordano A (2014) The gap between the physiological and therapeutic roles of mesenchymal stem cells. Med Res Rev 34(5):1100–1126

    Article  CAS  Google Scholar 

  30. Wakao S et al (2011) Multilineage-differentiating stress-enduring (muse) cells are a primary source of induced pluripotent stem cells in human fibroblasts. Proc Natl Acad Sci U S A 108(24):9875–9880

    Article  CAS  Google Scholar 

  31. Wakao S et al (2012) Regenerative effects of mesenchymal stem cells: contribution of muse cells, a novel pluripotent stem cell type that resides in mesenchymal cells. Cells 1(4):1045–1060

    Article  CAS  Google Scholar 

  32. Dezawa M (2016) Muse cells provide the pluripotency of mesenchymal stem cells: direct contribution of muse cells to tissue regeneration. Cell Transplant 25:849–861

    Article  Google Scholar 

  33. Alessio N et al (2018) Stress and stem cells: adult muse cells tolerate extensive genotoxic stimuli better than mesenchymal stromal cells. Oncotarget 9(27):19328–19341

    Article  Google Scholar 

  34. Freeman AK, Monteiro AN (2010) Phosphatases in the cellular response to DNA damage. Cell Commun Signal 8:27

    Article  Google Scholar 

  35. Shibata A et al (2011) Factors determining DNA double-strand break repair pathway choice in G2 phase. EMBO J 30(6):1079–1092

    Article  CAS  Google Scholar 

  36. Fu S et al (2012) gamma-H2AX kinetics as a novel approach to high content screening for small molecule radiosensitizers. PLoS One 7(6):e38465

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Experimental Medicine, Campania University “Luigi Vanvitelli”, Naples, Italy

    Tiziana Squillaro, Nicola Alessio, Giovanni Di Bernardo & Umberto Galderisi

  2. Genome and Stem Cell Center (GENKOK), Erciyes University, Kayseri, Turkey

    Servet Özcan & Umberto Galderisi

  3. Institute of Agro-Environmental and Forest Biology, CNR, Naples, Italy

    Gianfranco Peluso

  4. Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, PA, USA

    Umberto Galderisi

Authors
  1. Tiziana Squillaro
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  2. Nicola Alessio
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  3. Giovanni Di Bernardo
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  4. Servet Özcan
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  5. Gianfranco Peluso
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  6. Umberto Galderisi
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Corresponding author

Correspondence to Umberto Galderisi .

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Editors and Affiliations

  1. Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

    Mari Dezawa

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Squillaro, T., Alessio, N., Di Bernardo, G., Özcan, S., Peluso, G., Galderisi, U. (2018). Stem Cells and DNA Repair Capacity: Muse Stem Cells Are Among the Best Performers. In: Dezawa, M. (eds) Muse Cells. Advances in Experimental Medicine and Biology, vol 1103. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56847-6_5

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