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
Affiliations
- Glickman Urological and Kidney Institute, The Cleveland Clinic, Cleveland, OH 44195 USA. Electronic address: [email protected].
- 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
- Stem Cells Int. 2013;2013:130763 - PubMed
- Circulation. 2004 Mar 16;109(10):1292-8 - PubMed
- Brain. 2012 Nov;135(Pt 11):3298-310 - PubMed
- Int J Oncol. 2014 Jun;44(6):1789-98 - PubMed
- Int J Cardiol. 2013 Sep 30;168(2):1062-9 - PubMed
- Br J Haematol. 2013 Nov;163(4):501-9 - PubMed
- Am J Physiol Renal Physiol. 2007 May;292(5):F1626-35 - PubMed
- Cancer Invest. 2012 Aug;30(7):513-8 - PubMed
- Stem Cells Dev. 2012 Jun 10;21(9):1391-400 - PubMed
- Cell Stem Cell. 2012 Mar 2;10(3):244-58 - PubMed
- Biomacromolecules. 2011 May 9;12(5):1651-7 - PubMed
- J Am Soc Nephrol. 2007 Sep;18(9):2486-96 - PubMed
- Biochimie. 2013 Dec;95(12):2212-21 - PubMed
- Kidney Int. 2002 Feb;61(2):387-95 - PubMed
- Circ Res. 2008 Nov 21;103(11):1204-19 - PubMed
- Biomed Res Int. 2013;2013:930713 - PubMed
- Am J Physiol Heart Circ Physiol. 2009 Jun;296(6):H1888-97 - PubMed
- Nat Cell Biol. 2007 Jun;9(6):654-9 - PubMed
- Tissue Eng Part C Methods. 2010 Aug;16(4):735-49 - PubMed
- Urol Int. 2011;86(1):110-6 - PubMed
- Proteomics. 2013 May;13(10-11):1637-53 - PubMed
- Leukemia. 2006 May;20(5):847-56 - PubMed
- Nat Med. 2001 Mar;7(3):297-303 - PubMed
- Transl Stroke Res. 2013 Feb;4(1):76-88 - PubMed
- Methods Enzymol. 2006;420:64-81 - PubMed
- Cell Tissue Kinet. 1970 Oct;3(4):393-403 - PubMed
- J Inflamm (Lond). 2005 Jul 26;2:8 - PubMed
- Science. 1998 Nov 6;282(5391):1145-7 - PubMed
- J Am Coll Cardiol. 2009 Dec 8;54(24):2277-86 - PubMed
- Exp Hematol. 2000 Aug;28(8):875-84 - PubMed
- Circ Res. 2009 May 22;104(10):1209-16 - PubMed
- Cytotherapy. 2010;12(1):88-95 - PubMed
- J Cell Physiol. 2009 Jun;219(3):563-71 - PubMed
- Cell Transplant. 2014;23(11):1395-406 - PubMed
- J Neurosci Res. 2010 May 15;88(7):1394-405 - PubMed
- Nat Rev Urol. 2012 Aug;9(8):435-47 - PubMed
- Obstet Gynecol Int. 2012;2012:612946 - PubMed
- J Immunol. 2003 Oct 1;171(7):3426-34 - PubMed
- Cell Mol Life Sci. 1999 Apr;55(4):663-7 - PubMed
- J Exp Med. 1996 Mar 1;183(3):1161-72 - PubMed
- Biochimie. 2013 Dec;95(12):2235-45 - PubMed
- Circ Res. 2006 Jun 9;98(11):1414-21 - PubMed
- Proteomics. 2011 Feb;11(4):691-708 - PubMed
- Front Immunol. 2012 Sep 26;3:297 - PubMed
- Stem Cell Res. 2011 May;6(3):206-14 - PubMed
- Cell Transplant. 2014;23(9):1045-59 - PubMed
- Fibrogenesis Tissue Repair. 2010 Aug 05;3:13 - PubMed
- Curr Biol. 2011 May 10;21(9):779-86 - PubMed
- Stem Cells. 2006 Apr;24(4):1030-41 - PubMed
- Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13724-9 - PubMed
- Cell Cycle. 2011 Sep 15;10(18):3198-207 - PubMed
- J Proteome Res. 2010 Apr 5;9(4):1754-62 - PubMed
- J Am Heart Assoc. 2013 Oct;2(5):e000338 - PubMed
- J Tissue Eng Regen Med. 2011 Aug;5(8):668-72 - PubMed
- Stem Cells. 2012 Oct;30(10):2283-96 - PubMed
- PLoS One. 2013;8(8):e72604 - PubMed
- J Clin Invest. 2009 Dec;119(12):3678-91 - PubMed
- Gene Ther. 2011 Apr;18(4):394-402 - PubMed
- Cells. 2013 Sep 16;2(3):621-34 - PubMed
- Mol Cell Proteomics. 2007 Oct;6(10):1680-9 - PubMed
- Cancer Res. 2011 Aug 1;71(15):5346-56 - PubMed
- J Am Soc Nephrol. 2011 Apr;22(4):704-17 - PubMed
- Nat Rev Mol Cell Biol. 2009 Feb;10(2):148-55 - PubMed
- Curr Stem Cell Res Ther. 2010 Jun;5(2):103-10 - PubMed
- Prog Biophys Mol Biol. 2003 Sep;83(1):1-45 - PubMed
- Lancet. 2003 Aug 30;362(9385):697-703 - PubMed
- Circ Cardiovasc Genet. 2012 Feb 1;5(1):o8-o18 - PubMed
- Blood. 2006 Dec 1;108(12):3938-44 - PubMed
- Circulation. 2004 Mar 30;109(12):1543-9 - PubMed
- Kidney Int. 2011 Dec;80(11):1138-45 - PubMed
- Cell Transplant. 2012;21(8):1641-50 - PubMed
- Urology. 2010 Mar;75(3):718-23 - PubMed
- Gynecol Oncol. 2008 Jul;110(1):13-21 - PubMed
- Clin Sci (Lond). 2013 Feb;124(3):165-76 - PubMed
- Stem Cells Dev. 2013 Feb 15;22(4):643-53 - PubMed
- Pharmacol Ther. 2011 Jan;129(1):97-108 - PubMed
- Biomaterials. 2013 Jan;34(4):1311-26 - PubMed
- FASEB J. 2006 Apr;20(6):661-9 - PubMed
- Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):4003-8 - PubMed
- Lancet. 2004 Mar 6;363(9411):751-6 - PubMed
- Circulation. 2002 Jan 1;105(1):93-8 - PubMed
- Clin Cancer Res. 2010 Jan 15;16(2):461-73 - PubMed
- Biochimie. 2013 Dec;95(12):2196-211 - PubMed
- Int J Biochem Cell Biol. 2013 Mar;45(3):560-70 - PubMed
- Biochimie. 2013 Dec;95(12):2271-85 - PubMed
- J Sex Med. 2010 Oct;7(10):3331-40 - PubMed
- Am J Pathol. 1993 Nov;143(5):1377-88 - PubMed
- Eur J Neurosci. 2006 Apr;23(8):2119-34 - PubMed
- Cell Transplant. 2011;20(1):5-14 - PubMed
- Mol Ther. 2006 Dec;14(6):840-50 - PubMed
- PLoS One. 2012;7(6):e38746 - PubMed
- PLoS One. 2012;7(4):e35685 - PubMed
- J Cell Mol Med. 2007 Jan-Feb;11(1):21-38 - PubMed
- Mol Ther. 2010 Oct;18(10):1857-64 - PubMed
- Nature. 2011 May 19;473(7347):298-307 - PubMed
- Cell Biol Int. 2015 Feb;39(2):192-200 - PubMed
- Stem Cells. 2009 Oct;27(10):2383-92 - PubMed
- Urology. 2004 Apr;63(4):780-5 - PubMed
- Mol Ther. 2008 Apr;16(4):749-56 - PubMed
- J Cell Physiol. 2011 Aug;226(8):2131-8 - PubMed
- Science. 1999 Apr 2;284(5411):143-7 - PubMed
- J Crohns Colitis. 2008 Jun;2(2):99-106 - PubMed
- Circulation. 2012 Sep 11;126(11 Suppl 1):S20-8 - PubMed
- Stem Cells. 2007 Oct;25(10):2648-59 - PubMed
- Proc Natl Acad Sci U S A. 2010 Dec 7;107(49):21110-5 - PubMed
- J Am Coll Cardiol. 2010 Oct 12;56(16):1287-97 - PubMed
- Brain Pathol. 2004 Apr;14(2):131-6 - PubMed
- Med Hypotheses. 2014 Jun;82(6):670-3 - PubMed
- Stem Cells. 2012 Nov;30(11):2472-86 - PubMed
- Blood. 2002 May 15;99(10):3838-43 - PubMed
- Leukemia. 2009 May;23(5):925-33 - PubMed
- Nat Med. 2003 Sep;9(9):1195-201 - PubMed
- J Mol Cell Cardiol. 2011 Feb;50(2):280-9 - PubMed
- Blood. 2004 Nov 1;104(9):2643-5 - PubMed
- Stem Cells. 2007 Sep;25(9):2363-70 - PubMed
- J Exp Med. 2002 May 20;195(10):1303-16 - PubMed
- Stem Cell Reports. 2014 May 6;2(5):606-19 - PubMed
- Ann Thorac Surg. 2005 Jul;80(1):229-36; discussion 236-7 - PubMed
- Proc Natl Acad Sci U S A. 1981 Dec;78(12):7634-8 - PubMed
- Stem Cells. 2012 Jul;30(7):1556-64 - PubMed
MeSH terms
Publication Types
Grant support