Display options
Share it on

Neural Regen Res. 2015 Jun;10(6):850-8. doi: 10.4103/1673-5374.158352.

Mesenchymal stem cells-based therapy as a potential treatment in neurodegenerative disorders: is the escape from senescence an answer?.

Neural regeneration research

Alessandro Castorina, Marta Anna Szychlinska, Rubina Marzagalli, Giuseppe Musumeci

Affiliations

  1. Department of Biomedical and Biotechnological Science, Section of Human Anatomy and Histology, School of Medicine, University of Catania, Via S. Sofia 87, Catania, Italy.

PMID: 26199588 PMCID: PMC4498333 DOI: 10.4103/1673-5374.158352

Abstract

Aging is the most prominent risk factor contributing to the development of neurodegenerative disorders. In the United States, over 35 million of elderly people suffer from age-related diseases. Aging impairs the self-repair ability of neuronal cells, which undergo progressive deterioration. Once initiated, this process hampers the already limited regenerative power of the central nervous system, making the search for new therapeutic strategies particularly difficult in elderly affected patients. So far, mesenchymal stem cells have proven to be a viable option to ameliorate certain aspects of neurodegeneration, as they possess high proliferative rate and differentiate in vitro into multiple lineages. However, accumulating data have demonstrated that during long-term culture, mesenchymal stem cells undergo spontaneous transformation. Transformed mesenchymal stem cells show typical features of senescence, including the progressive shortening of telomers, which results in cell loss and, as a consequence, hampered regenerative potential. These evidences, in line with those observed in mesenchymal stem cells isolated from old donors, suggest that senescence may represent a limit to mesenchymal stem cells exploitation in therapy, prompting scholars to either find alternative sources of pluripotent cells or to arrest the age-related transformation. In the present review, we summarize findings from recent literature, and critically discuss some of the major hurdles encountered in the search of appropriate sources of mesenchymal stem cells, as well as benefits arising from their use in neurodegenerative diseases. Finally, we provide some insights that may aid in the development of strategies to arrest or, at least, delay the aging of mesenchymal stem cells to improve their therapeutic potential.

Keywords: MSCs; aging; cellular therapy; neurodegenerative disorders; telomere shortening

References

  1. Mech Ageing Dev. 2002 Apr;123(7):811-7 - PubMed
  2. EMBO Mol Med. 2009 Nov;1(8-9):360-70 - PubMed
  3. Bone. 2007 Feb;40(2):382-90 - PubMed
  4. Cytotherapy. 2013 Mar;15(3):330-43 - PubMed
  5. J Dent Res. 2009 Sep;88(9):792-806 - PubMed
  6. Int J Mol Sci. 2015 Mar 13;16(3):5922-44 - PubMed
  7. Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1283-8 - PubMed
  8. PLoS One. 2015 Feb 06;10(2):e0117799 - PubMed
  9. Peptides. 2013 Jan;39:119-24 - PubMed
  10. Mol Biol Cell. 2002 Dec;13(12):4279-95 - PubMed
  11. Stem Cell Res. 2012 Mar;8(2):215-25 - PubMed
  12. Ageing Res Rev. 2012 Jan;11(1):104-22 - PubMed
  13. Biomed Mater Eng. 2015;25(1 Suppl):41-6 - PubMed
  14. J Neurol Sci. 2008 Mar 15;266(1-2):57-62 - PubMed
  15. J Neuropsychiatry Clin Neurosci. 2015;27(2):e92-6 - PubMed
  16. Biomed Pharmacother. 2008 Apr-May;62(4):218-32 - PubMed
  17. Curr Stem Cell Res Ther. 2014;9(6):513-21 - PubMed
  18. J Neurosci Res. 2013 May;91(5):660-70 - PubMed
  19. J Cell Biochem. 2006 Aug 1;98(5):1076-84 - PubMed
  20. Int J Mol Sci. 2014 Dec 24;16(1):193-217 - PubMed
  21. Cell. 1997 Aug 8;90(3):549-58 - PubMed
  22. World J Orthop. 2014 Apr 18;5(2):80-8 - PubMed
  23. Indian J Clin Biochem. 2011 Jan;26(1):78-81 - PubMed
  24. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10114-8 - PubMed
  25. Br J Pharmacol. 2013 Jun;169(3):512-23 - PubMed
  26. Stem Cells Dev. 2015 Apr 15;24(8):973-82 - PubMed
  27. Nat Rev Neurosci. 2006 Jan;7(1):30-40 - PubMed
  28. Peptides. 2012 Sep;37(1):32-9 - PubMed
  29. Exp Cell Res. 2011 Dec 10;317(20):2950-7 - PubMed
  30. J Bone Miner Res. 2010 Oct;25(10):2138-47 - PubMed
  31. Lancet Neurol. 2011 Jul;10(7):649-56 - PubMed
  32. Trends Biochem Sci. 2002 Jul;27(7):339-44 - PubMed
  33. Cell Mol Life Sci. 2013 Oct;70(20):3871-82 - PubMed
  34. J Neurochem. 2010 Mar;112(6):1527-38 - PubMed
  35. Cell Prolif. 2011 Feb;44(1):67-74 - PubMed
  36. Histol Histopathol. 2015 Jan;30(1):1-12 - PubMed
  37. Nat Rev Genet. 2007 Apr;8(4):299-309 - PubMed
  38. J Clin Invest. 2012 Jan;122(1):80-90 - PubMed
  39. Histochem Cell Biol. 2014 Sep;142(3):257-67 - PubMed
  40. J Neurosci Res. 2000 Aug 15;61(4):364-70 - PubMed
  41. Eur J Neurol. 2014;21(1):93-9 - PubMed
  42. Regen Med. 2007 Jan;2(1):37-49 - PubMed
  43. Magn Reson Imaging. 2009 Jan;27(1):142-5 - PubMed
  44. Tissue Eng. 2001 Apr;7(2):211-28 - PubMed
  45. Front Biosci (Landmark Ed). 2011 Jun 01;16:2695-733 - PubMed
  46. J Clin Neuropsychol. 1981 May;3(1):33-42 - PubMed
  47. J Cell Mol Med. 2012 Oct;16(10):2518-29 - PubMed
  48. J Gerontol A Biol Sci Med Sci. 2014 Nov;69(11):1331-8 - PubMed
  49. Eur J Hum Genet. 2013 Oct;21(10):1163-8 - PubMed
  50. Scand J Med Sci Sports. 2015 Apr;25(2):e222-30 - PubMed
  51. Mutat Res. 2012 Feb 1;730(1-2):12-9 - PubMed
  52. Neurology. 2005 Apr 12;64(7):1152-6 - PubMed
  53. Stroke. 2013 Feb;44(2):551-4 - PubMed
  54. Proc Natl Acad Sci U S A. 2003 May 13;100(10):5807-12 - PubMed
  55. Nat Neurosci. 2003 Mar;6(3):309-15 - PubMed
  56. Ageing Res Rev. 2010 Jul;9(3):245-56 - PubMed
  57. FEBS J. 2013 Jul;280(14):3180-93 - PubMed
  58. Mol Cell Neurosci. 2012 Mar;49(3):271-81 - PubMed
  59. Bioessays. 2008 Feb;30(2):102-6 - PubMed
  60. Cell Biol Int. 2014 Dec;38(12):1367-83 - PubMed
  61. Nat Rev Mol Cell Biol. 2012 May 16;13(6):397-404 - PubMed
  62. Nat Rev Neurosci. 2004 Feb;5(2):87-96 - PubMed
  63. Amyotroph Lateral Scler Other Motor Neuron Disord. 2003 Sep;4(3):158-61 - PubMed
  64. Ageing Res Rev. 2010 Nov;9 Suppl 1:S36-46 - PubMed
  65. Neurosci Lett. 2010 May 14;475(2):99-103 - PubMed
  66. J Neurosci. 2006 May 31;26(22):6103-14 - PubMed
  67. Acta Histochem. 2014 Oct;116(8):1407-17 - PubMed
  68. PLoS One. 2014 Oct 29;9(10):e110963 - PubMed
  69. Injury. 2009 Feb;40(2):150-7 - PubMed
  70. Cereb Cortex. 2005 Nov;15(11):1676-89 - PubMed
  71. J Mol Neurosci. 2012 Nov;48(3):674-83 - PubMed
  72. BMC Cell Biol. 2008 Oct 28;9:60 - PubMed
  73. Neurobiol Aging. 2000 Sep-Oct;21(5):683-8 - PubMed
  74. Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11474-9 - PubMed
  75. Synapse. 1998 Sep;30(1):56-61 - PubMed
  76. Stem Cell Rev. 2012 Jun;8(2):375-92 - PubMed
  77. Nature. 2007 Jun 21;447(7147):924-31 - PubMed
  78. Trends Neurosci. 2014 May;37(5):256-63 - PubMed
  79. Mech Ageing Dev. 2008 Mar;129(3):163-73 - PubMed
  80. J Neurochem. 2014 Oct;131(2):206-18 - PubMed
  81. Spine (Phila Pa 1976). 2011 Jun;36(13):997-1005 - PubMed
  82. Am J Pathol. 2009 Feb;174(2):574-85 - PubMed
  83. Arthritis Rheum. 2010 Oct;62(10):3036-47 - PubMed
  84. Maturitas. 2014 Jul;78(3):188-98 - PubMed
  85. Cell Biol Int. 2012 Aug 1;36(8):747-53 - PubMed
  86. J Neuropathol Exp Neurol. 1997 May;56(5):523-30 - PubMed
  87. Annu Rev Med. 2007;58:313-28 - PubMed
  88. J Alzheimers Dis. 2011;26 Suppl 3:159-99 - PubMed
  89. Science. 2012 Jun 22;336(6088):1549-54 - PubMed
  90. Discov Med. 2012 Jun;13(73):451-60 - PubMed
  91. PLoS One. 2010 Dec 20;5(12):e15299 - PubMed
  92. Neurosci Lett. 2006 Oct 9;406(3):260-4 - PubMed
  93. Odontology. 2013 Jul;101(2):121-32 - PubMed
  94. Exp Biol Med (Maywood). 2011 Nov;236(11):1333-41 - PubMed
  95. Acta Naturae. 2012 Apr;4(2):44-61 - PubMed
  96. Curr Alzheimer Res. 2009 Feb;6(1):36-47 - PubMed
  97. Tissue Eng. 2006 Oct;12(10):2813-23 - PubMed
  98. Trends Genet. 1993 Jul;9(7):246-9 - PubMed
  99. Int J Mol Sci. 2012;13(7):8430-48 - PubMed
  100. J Gerontol A Biol Sci Med Sci. 2012 Apr;67(4):330-5 - PubMed
  101. Nat Genet. 1996 Jul;13(3):350-3 - PubMed
  102. Mech Ageing Dev. 2008 Apr;129(4):183-90 - PubMed
  103. Neuroimmunomodulation. 2015;22(4):233-42 - PubMed
  104. J Can Acad Child Adolesc Psychiatry. 2011 Nov;20(4):265-76 - PubMed
  105. Cell Mol Life Sci. 2010 Feb;67(4):655-69 - PubMed
  106. Trends Neurosci. 2004 Oct;27(10):607-13 - PubMed
  107. J Neurosci Res. 2009 Jul;87(9):2034-46 - PubMed
  108. Neurol Res. 2015 Apr;37(4):309-19 - PubMed
  109. Exp Cell Res. 2014 Mar 10;322(1):108-21 - PubMed
  110. PLoS One. 2012;7(9):e45052 - PubMed

Publication Types