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Adv Drug Deliv Rev. 2015 Mar;82:1-11. doi: 10.1016/j.addr.2014.10.007. Epub 2014 Oct 15.

Stem cells as drug delivery methods: application of stem cell secretome for regeneration.

Advanced drug delivery reviews

Christine Tran, Margot S Damaser

Affiliations

  1. Glickman Urological and Kidney Institute, The Cleveland Clinic, Cleveland, OH 44195 USA. Electronic address: [email protected].
  2. Cleveland Clinic Lerner College of Medicine, Lerner Research Institute, Glickman Urological and Kidney Institute, The Cleveland Clinic, Cleveland, OH 44195 USA. Electronic address: [email protected].

PMID: 25451858 PMCID: PMC4398586 DOI: 10.1016/j.addr.2014.10.007

Abstract

Mesenchymal stem cells (MSCs) are a unique cell population defined by their ability to indefinitely self-renew, differentiate into multiple cell lineages, and form clonal cell populations. It was originally thought that this ability for broad plasticity defined the therapeutic potential of MSCs. However, an expanding body of recent literature has brought growing awareness to the remarkable array of bioactive molecules produced by stem cells. This protein milieu or "secretome" comprises a diverse host of cytokines, chemokines, angiogenic factors, and growth factors. The autocrine/paracrine role of these molecules is being increasingly recognized as key to the regulation of many physiological processes including directing endogenous and progenitor cells to sites of injury as well as mediating apoptosis, scarring, and tissue revascularization. In fact, the immunomodulatory and paracrine role of these molecules may predominantly account for the therapeutic effects of MSCs given that many in vitro and in vivo studies have demonstrated limited stem cell engraftment at the site of injury. While the study of such a vast protein array remains challenging, technological advances in the field of proteomics have greatly facilitated our ability to analyze and characterize the stem cell secretome. Thus, stem cells can be considered as tunable pharmacological storehouses useful for combinatorial drug manufacture and delivery. As a cell-free option for regenerative medicine therapies, stem cell secretome has shown great potential in a variety of clinical applications including the restoration of function in cardiovascular, neurodegenerative, oncologic, and genitourinary pathologies.

Published by Elsevier B.V.

Keywords: Mechanism of action; Mesenchymal stem cells; Regenerative medicine; Secretions; Systemic therapy; Tissue engineering

References

  1. Stem Cells Int. 2013;2013:130763 - PubMed
  2. Circulation. 2004 Mar 16;109(10):1292-8 - PubMed
  3. Brain. 2012 Nov;135(Pt 11):3298-310 - PubMed
  4. Int J Oncol. 2014 Jun;44(6):1789-98 - PubMed
  5. Int J Cardiol. 2013 Sep 30;168(2):1062-9 - PubMed
  6. Br J Haematol. 2013 Nov;163(4):501-9 - PubMed
  7. Am J Physiol Renal Physiol. 2007 May;292(5):F1626-35 - PubMed
  8. Cancer Invest. 2012 Aug;30(7):513-8 - PubMed
  9. Stem Cells Dev. 2012 Jun 10;21(9):1391-400 - PubMed
  10. Cell Stem Cell. 2012 Mar 2;10(3):244-58 - PubMed
  11. Biomacromolecules. 2011 May 9;12(5):1651-7 - PubMed
  12. J Am Soc Nephrol. 2007 Sep;18(9):2486-96 - PubMed
  13. Biochimie. 2013 Dec;95(12):2212-21 - PubMed
  14. Kidney Int. 2002 Feb;61(2):387-95 - PubMed
  15. Circ Res. 2008 Nov 21;103(11):1204-19 - PubMed
  16. Biomed Res Int. 2013;2013:930713 - PubMed
  17. Am J Physiol Heart Circ Physiol. 2009 Jun;296(6):H1888-97 - PubMed
  18. Nat Cell Biol. 2007 Jun;9(6):654-9 - PubMed
  19. Tissue Eng Part C Methods. 2010 Aug;16(4):735-49 - PubMed
  20. Urol Int. 2011;86(1):110-6 - PubMed
  21. Proteomics. 2013 May;13(10-11):1637-53 - PubMed
  22. Leukemia. 2006 May;20(5):847-56 - PubMed
  23. Nat Med. 2001 Mar;7(3):297-303 - PubMed
  24. Transl Stroke Res. 2013 Feb;4(1):76-88 - PubMed
  25. Methods Enzymol. 2006;420:64-81 - PubMed
  26. Cell Tissue Kinet. 1970 Oct;3(4):393-403 - PubMed
  27. J Inflamm (Lond). 2005 Jul 26;2:8 - PubMed
  28. Science. 1998 Nov 6;282(5391):1145-7 - PubMed
  29. J Am Coll Cardiol. 2009 Dec 8;54(24):2277-86 - PubMed
  30. Exp Hematol. 2000 Aug;28(8):875-84 - PubMed
  31. Circ Res. 2009 May 22;104(10):1209-16 - PubMed
  32. Cytotherapy. 2010;12(1):88-95 - PubMed
  33. J Cell Physiol. 2009 Jun;219(3):563-71 - PubMed
  34. Cell Transplant. 2014;23(11):1395-406 - PubMed
  35. J Neurosci Res. 2010 May 15;88(7):1394-405 - PubMed
  36. Nat Rev Urol. 2012 Aug;9(8):435-47 - PubMed
  37. Obstet Gynecol Int. 2012;2012:612946 - PubMed
  38. J Immunol. 2003 Oct 1;171(7):3426-34 - PubMed
  39. Cell Mol Life Sci. 1999 Apr;55(4):663-7 - PubMed
  40. J Exp Med. 1996 Mar 1;183(3):1161-72 - PubMed
  41. Biochimie. 2013 Dec;95(12):2235-45 - PubMed
  42. Circ Res. 2006 Jun 9;98(11):1414-21 - PubMed
  43. Proteomics. 2011 Feb;11(4):691-708 - PubMed
  44. Front Immunol. 2012 Sep 26;3:297 - PubMed
  45. Stem Cell Res. 2011 May;6(3):206-14 - PubMed
  46. Cell Transplant. 2014;23(9):1045-59 - PubMed
  47. Fibrogenesis Tissue Repair. 2010 Aug 05;3:13 - PubMed
  48. Curr Biol. 2011 May 10;21(9):779-86 - PubMed
  49. Stem Cells. 2006 Apr;24(4):1030-41 - PubMed
  50. Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13724-9 - PubMed
  51. Cell Cycle. 2011 Sep 15;10(18):3198-207 - PubMed
  52. J Proteome Res. 2010 Apr 5;9(4):1754-62 - PubMed
  53. J Am Heart Assoc. 2013 Oct;2(5):e000338 - PubMed
  54. J Tissue Eng Regen Med. 2011 Aug;5(8):668-72 - PubMed
  55. Stem Cells. 2012 Oct;30(10):2283-96 - PubMed
  56. PLoS One. 2013;8(8):e72604 - PubMed
  57. J Clin Invest. 2009 Dec;119(12):3678-91 - PubMed
  58. Gene Ther. 2011 Apr;18(4):394-402 - PubMed
  59. Cells. 2013 Sep 16;2(3):621-34 - PubMed
  60. Mol Cell Proteomics. 2007 Oct;6(10):1680-9 - PubMed
  61. Cancer Res. 2011 Aug 1;71(15):5346-56 - PubMed
  62. J Am Soc Nephrol. 2011 Apr;22(4):704-17 - PubMed
  63. Nat Rev Mol Cell Biol. 2009 Feb;10(2):148-55 - PubMed
  64. Curr Stem Cell Res Ther. 2010 Jun;5(2):103-10 - PubMed
  65. Prog Biophys Mol Biol. 2003 Sep;83(1):1-45 - PubMed
  66. Lancet. 2003 Aug 30;362(9385):697-703 - PubMed
  67. Circ Cardiovasc Genet. 2012 Feb 1;5(1):o8-o18 - PubMed
  68. Blood. 2006 Dec 1;108(12):3938-44 - PubMed
  69. Circulation. 2004 Mar 30;109(12):1543-9 - PubMed
  70. Kidney Int. 2011 Dec;80(11):1138-45 - PubMed
  71. Cell Transplant. 2012;21(8):1641-50 - PubMed
  72. Urology. 2010 Mar;75(3):718-23 - PubMed
  73. Gynecol Oncol. 2008 Jul;110(1):13-21 - PubMed
  74. Clin Sci (Lond). 2013 Feb;124(3):165-76 - PubMed
  75. Stem Cells Dev. 2013 Feb 15;22(4):643-53 - PubMed
  76. Pharmacol Ther. 2011 Jan;129(1):97-108 - PubMed
  77. Biomaterials. 2013 Jan;34(4):1311-26 - PubMed
  78. FASEB J. 2006 Apr;20(6):661-9 - PubMed
  79. Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):4003-8 - PubMed
  80. Lancet. 2004 Mar 6;363(9411):751-6 - PubMed
  81. Circulation. 2002 Jan 1;105(1):93-8 - PubMed
  82. Clin Cancer Res. 2010 Jan 15;16(2):461-73 - PubMed
  83. Biochimie. 2013 Dec;95(12):2196-211 - PubMed
  84. Int J Biochem Cell Biol. 2013 Mar;45(3):560-70 - PubMed
  85. Biochimie. 2013 Dec;95(12):2271-85 - PubMed
  86. J Sex Med. 2010 Oct;7(10):3331-40 - PubMed
  87. Am J Pathol. 1993 Nov;143(5):1377-88 - PubMed
  88. Eur J Neurosci. 2006 Apr;23(8):2119-34 - PubMed
  89. Cell Transplant. 2011;20(1):5-14 - PubMed
  90. Mol Ther. 2006 Dec;14(6):840-50 - PubMed
  91. PLoS One. 2012;7(6):e38746 - PubMed
  92. PLoS One. 2012;7(4):e35685 - PubMed
  93. J Cell Mol Med. 2007 Jan-Feb;11(1):21-38 - PubMed
  94. Mol Ther. 2010 Oct;18(10):1857-64 - PubMed
  95. Nature. 2011 May 19;473(7347):298-307 - PubMed
  96. Cell Biol Int. 2015 Feb;39(2):192-200 - PubMed
  97. Stem Cells. 2009 Oct;27(10):2383-92 - PubMed
  98. Urology. 2004 Apr;63(4):780-5 - PubMed
  99. Mol Ther. 2008 Apr;16(4):749-56 - PubMed
  100. J Cell Physiol. 2011 Aug;226(8):2131-8 - PubMed
  101. Science. 1999 Apr 2;284(5411):143-7 - PubMed
  102. J Crohns Colitis. 2008 Jun;2(2):99-106 - PubMed
  103. Circulation. 2012 Sep 11;126(11 Suppl 1):S20-8 - PubMed
  104. Stem Cells. 2007 Oct;25(10):2648-59 - PubMed
  105. Proc Natl Acad Sci U S A. 2010 Dec 7;107(49):21110-5 - PubMed
  106. J Am Coll Cardiol. 2010 Oct 12;56(16):1287-97 - PubMed
  107. Brain Pathol. 2004 Apr;14(2):131-6 - PubMed
  108. Med Hypotheses. 2014 Jun;82(6):670-3 - PubMed
  109. Stem Cells. 2012 Nov;30(11):2472-86 - PubMed
  110. Blood. 2002 May 15;99(10):3838-43 - PubMed
  111. Leukemia. 2009 May;23(5):925-33 - PubMed
  112. Nat Med. 2003 Sep;9(9):1195-201 - PubMed
  113. J Mol Cell Cardiol. 2011 Feb;50(2):280-9 - PubMed
  114. Blood. 2004 Nov 1;104(9):2643-5 - PubMed
  115. Stem Cells. 2007 Sep;25(9):2363-70 - PubMed
  116. J Exp Med. 2002 May 20;195(10):1303-16 - PubMed
  117. Stem Cell Reports. 2014 May 6;2(5):606-19 - PubMed
  118. Ann Thorac Surg. 2005 Jul;80(1):229-36; discussion 236-7 - PubMed
  119. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7634-8 - PubMed
  120. Stem Cells. 2012 Jul;30(7):1556-64 - PubMed

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