Mesenchymal Stem Cells: Possibilities of New Treatment Options

  • Zeynep Tokcaer-Keskin
  • Hande Kocak
  • Ihsan Gursel
  • Kamil C. Akcali
Chapter
First Online:
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)

Abstract

Stem cell research evolved as a new hope and has gained tremendous interest during the last two decades in developing potential strategies for many debilitating diseases. Mesenchymal stem cells (MSCs) are bone marrow-derived multipotent stem cells capable of self-renewal and of differentiating into multiple lineages, such as osteocytes, adipocytes, chondrocytes, myoblasts, cardiomyocytes, and hepatocytes. MSCs are an important source for cellular therapies. They can easily be obtained and expanded in vitro in large numbers without significantly altering their properties. MSCs not only migrate to the injured site in vivo but also have immunomodulatory effects that make their use attractive for allogeneic grafting. MSCs can also be frozen for preservation; and when thawed, they retain their normal physiological function, allowing future “off-the-shelf” therapy approaches. Because of these features, MSCs have high therapeutic value in tissue engineering and regenerative medicine. In this chapter, the contribution of the MSCs to cardiovascular repair and liver regeneration are summarized.

Keywords

Stem Cell Mesenchymal Stem Cell Hepatocyte Growth Fact Liver Regeneration Osteogenesis Imperfecta 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Notes

Acknowledgments

This work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK): grants SBAG105S393 to K.C.A. and SBAG106S102 and SBAG108S316 to I.G.

References

  1. Abdel Aziz MT, Atta HM, Mahfouz S et al (2007) Therapeutic potential of bone marrow-derived mesenchymal stem cells on experimental liver fibrosis. Clin Biochem 40:893–899PubMedCrossRefGoogle Scholar
  2. Aggrawal S, Pitteger MF (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105:1815–1822CrossRefGoogle Scholar
  3. Akar AR, Durdu S, Corapcioglu T et al (2006) Regenerative medicine for cardiovascular disorders: new milestones—adult stem cells. Artif Organs 30:213–232PubMedCrossRefGoogle Scholar
  4. Banas A, Teratani T, Yamamoto Y et al (2008) IFATS collection: in vivo therapeutic potential of human adipose tissue mesenchymal stem cells after transplantation into mice with liver injury. Stem Cells 26:2705–2712PubMedCrossRefGoogle Scholar
  5. Bartholomew A, Sturgeon C, Siatskas M et al (2002) Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 30:42–48PubMedCrossRefGoogle Scholar
  6. Block GJ, Ohkouchi S, Fung F et al (2009) Multipotent stromal cells are activated to reduce apoptosis in part by upregulation and secretion of stanniocalcin-1. Stem Cells 27:670–681PubMedGoogle Scholar
  7. Caplan AI, Dennis JE (2006) Mesenchymal stem cells as trophic mediators. J Cell Biochem 98:1076–1084PubMedCrossRefGoogle Scholar
  8. Carvalho AB, Quintanilha LF, Dias JV et al (2008) Bone marrow multipotent mesenchymal stromal cells do not reduce fibrosis or improve function in a rat model of severe chronic liver injury. Stem Cells 26:1307–1314PubMedCrossRefGoogle Scholar
  9. Chamberlain J, Yamagami T, Colletti E et al (2007) Efficient generation of human hepatocytes by the intrahepatic delivery of clonal human mesenchymal stem cells in fetal sheep. Hepatology 46:1935–1945PubMedCrossRefGoogle Scholar
  10. Chen SL, Fang WW, Ye F et al (2004) Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. Am J Cardiol 94:92–95PubMedCrossRefGoogle Scholar
  11. Chen Y, Xiang LX, Shao JZ et al (2010) Recruitment of endogenous bone marrow mesenchymal stem cells towards injured liver. J Cell Mol Med 14:1494–1508PubMedCrossRefGoogle Scholar
  12. da Silva Meirelles L, Caplan AI, Nardi NB (2008) In search of the in vivo identity of mesenchymal stem cells. Stem Cells 26:2287–2299PubMedCrossRefGoogle Scholar
  13. De Becker A, Van Hummelen P, Bakkus M et al (2007) Migration of culture-expanded human mesenchymal stem cells through bone marrow endothelium is regulated by matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-3. Haematologica 92:440–449PubMedCrossRefGoogle Scholar
  14. Di Nicola M, Carlo-Stella C, Magni M et al (2002) Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99:3838–3843PubMedCrossRefGoogle Scholar
  15. Dominici M, Le Blanc K, Mueller I et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells: the International Society for Cellular Therapy position statement. Cytotherapy 8:315–317PubMedCrossRefGoogle Scholar
  16. Dong XJ, Zhang H, Pan RL et al (2010) Identification of cytokines involved in hepatic differentiation of mBM-MSCs under liver-injury conditions. World J Gastroenterol 16:3267–3278PubMedCrossRefGoogle Scholar
  17. Fang B, Shi M, Liao L et al (2004) Systemic infusion of FLK1(+) mesenchymal stem cells ameliorate carbon tetrachloride-induced liver fibrosis in mice. Transplantation 78:83–88PubMedCrossRefGoogle Scholar
  18. Friedenstein AJ, Petrakova KV, Kurolesova AI et al (1968) Heterotopic of bone marrow: analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 6:230–247PubMedCrossRefGoogle Scholar
  19. Grauss RW, Winter EM, van Tuyn J et al (2007) Mesenchymal stem cells from ischemic heart disease patients improve left ventricular function after acute myocardial infarction. Am J Physiol Heart Circ Physiol 293:H2438–H2447PubMedCrossRefGoogle Scholar
  20. Herrera MB, Bussolati B, Bruno S et al (2004) Mesenchymal stem cells contribute to the renal repair of acute tubular epithelial injury. Int J Mol Med 14:1035–1041PubMedGoogle Scholar
  21. Hung SC, Pochampally RR, Hsu SC et al (2007) Short-term exposure of multipotent stromal cells to low oxygen increases their expression of CX3CR1 and CXCR4 and their engraftment in vivo. PLoS One 2:e416PubMedCrossRefGoogle Scholar
  22. Inoue S, Popp FC, Koehl GE et al (2006) Immunomodulatory effects of mesenchymal stem cells in a rat organ transplant model. Transplantation 81:1589–1595PubMedCrossRefGoogle Scholar
  23. Jiang CY, Gui C, He AN et al (2008) Optimal time for mesenchymal stem cell transplantation in rats with myocardial infarction. J Zhejiang Univ Sci B 9:630–637PubMedCrossRefGoogle Scholar
  24. Katritsis DG, Sotiropoulou PA, Karvouni E et al (2005) Transcoronary transplantation of autologous mesenchymal stem cells and endothelial progenitors into infarcted human myocardium. Catheter Cardiovasc Interv 65:321–329PubMedCrossRefGoogle Scholar
  25. Krampera M, Glennie S, Dyson J et al (2003) Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood 101:3722–3729PubMedCrossRefGoogle Scholar
  26. Lanotte M, Allen TD, Dexter TM (1981) Histochemical and ultrastructural characteristics of a cell line from human bone-marrow stroma. J Cell Sci 50:281–297PubMedGoogle Scholar
  27. Le Blanc K, Tammik L, Sundberg B et al (2003) Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol 57:11–20PubMedCrossRefGoogle Scholar
  28. Lee KD, Kuo TK, Whang-Peng J et al (2004) In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology 40:1275–1284PubMedCrossRefGoogle Scholar
  29. Lim SY, Kim YS, Ahn Y (2006) The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial infarction model. Cardiovasc Res 70:530–542PubMedCrossRefGoogle Scholar
  30. Mangi AA, Noiseux N, Kong D et al (2003) Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med 9:1195–1201PubMedCrossRefGoogle Scholar
  31. Minguell JJ, Erices A, Conget P (2001) Mesenchymal stem cells. Exp Biol Med 226:507–520Google Scholar
  32. Morrison SJ, Shah NM, Anderson DJ (1997) Regulatory mechanisms in stem cell biology. Cell 88:287–298PubMedCrossRefGoogle Scholar
  33. Nasef A, Chapel A, Mazurier C et al (2007) Identification of IL-10 and TGF-beta transcripts involved in the inhibition of T-lymphocyte proliferation during cell contact with human mesenchymal stem cells. Gene Expr 13:217–226PubMedCrossRefGoogle Scholar
  34. Németh K, Leelahavanichkul A, Yuen PS et al (2009) Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med 15:42–49PubMedCrossRefGoogle Scholar
  35. Oyagi S, Hirose M, Kojima M et al (2006) Therapeutic effect of transplanting HGF-treated bone marrow mesenchymal cells into CCl4-injured rats. J Hepatol 44:742–748PubMedCrossRefGoogle Scholar
  36. Parekkadan B, van Poll D, Megeed Z et al (2007) Immunomodulation of activated hepatic stellate cells by mesenchymal stem cells. Biochem Biophys Res Commun 363:247–252PubMedCrossRefGoogle Scholar
  37. Perin EC, Silva GV, Assad JA et al (2008) Comparison of intracoronary and transendocardial delivery of allogeneic mesenchymal cells in a canine model of acute myocardial infarction. J Mol Cell Cardiol 44:486–495PubMedCrossRefGoogle Scholar
  38. Pervsner-Fischer M, Morad V, Cohen-Sfady M et al (2007) Toll-like receptors and their ligands control mesenchymal stem cell functions. Blood 109:1422–1432CrossRefGoogle Scholar
  39. Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147PubMedCrossRefGoogle Scholar
  40. Pulavendran S, Vignesh J, Rose C (2010) Differential anti-inflammatory and anti-fibrotic activity of transplanted mesenchymal vs. hematopoietic stem cells in carbon tetrachloride-induced liver injury in mice. Int Immunopharmacol 10:513–519PubMedCrossRefGoogle Scholar
  41. Rafei M, Hsieh J, Fortier S et al (2008) Mesenchymal stromal cell-derived CCL2 suppresses plasma cell immunoglobulin production via STAT3 inactivation and PAX5 induction. Blood 112:4991–4998PubMedCrossRefGoogle Scholar
  42. Rasmusson I (2006) Immune modulation by mesenchymal stem cells. Exp Cell Res 312: 2169–2179PubMedCrossRefGoogle Scholar
  43. Sackstein R, Merzaban JS, Cain DW et al (2008) Ex vivo glycan engineering of CD44 programs human multipotent mesenchymal stromal cell trafficking to bone. Nat Med 14:181–187PubMedCrossRefGoogle Scholar
  44. Sakaida I, Terai S, Yamamoto N et al (2004) Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice. Hepatology 40:1304–1311PubMedCrossRefGoogle Scholar
  45. Salem HK, Thiemermann C (2010) Mesenchymal stromal cells: current understanding and clinical status. Stem Cells 28:585–596PubMedGoogle Scholar
  46. Sato Y, Araki H, Kato J et al (2005) Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood 106:756–763PubMedCrossRefGoogle Scholar
  47. Segers VF, Van Riet I, Andries LJ et al (2006) Mesenchymal stem cell adhesion to cardiac microvascular endothelium: activators and mechanisms. Am J Physiol Heart Circ Physiol 290:H1370–H1377PubMedCrossRefGoogle Scholar
  48. Serralta A, Donato MT, Orbis F et al (2003) Functionality of cultured human hepatocytes from elective samples, cadaveric grafts and hepatectomies. Toxicol In Vitro 17:769–774PubMedCrossRefGoogle Scholar
  49. Serralta A, Donato MT, Martinez A et al (2005) Influence of preservation solution on the isolation and culture of human hepatocytes from liver grafts. Cell Transplant 14:837–843PubMedCrossRefGoogle Scholar
  50. Shake JG, Gruber PJ, Baumgartner WA et al (2002) Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects. Ann Thorac Surg 73: 1919–1925PubMedCrossRefGoogle Scholar
  51. Shi M, Li J, Liao L et al (2007) Regulation of CXCR4 expression in human mesenchymal stem cells by cytokine treatment: role in homing efficiency in NOD/SCID mice. Haematologica 92:897–904PubMedCrossRefGoogle Scholar
  52. Silva GV, Litovsky S, Assad JA et al (2005) Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation 111:150–156PubMedCrossRefGoogle Scholar
  53. Sotiropoulou PA, Perez SA, Gritzapis AD et al (2006) Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells 24:74–85PubMedCrossRefGoogle Scholar
  54. Tang J, Xie Q, Pan G et al (2006) Mesenchymal stem cells participate in angiogenesis and improve heart function in rat model of myocardial ischemia with reperfusion. Eur J Cardiothorac Surg 30:353–361PubMedCrossRefGoogle Scholar
  55. Till JE, Mcculloch EA (1961) A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res 14:213–222PubMedCrossRefGoogle Scholar
  56. Tögel F, Weiss K, Yang Y et al (2007) Vasculotropic, paracrine actions of infused mesenchymal stem cells are important to the recovery from acute kidney injury. Am J Physiol Renal Physiol 292:F1626–F1635PubMedCrossRefGoogle Scholar
  57. Tokcaer-Keskin Z, Akar AR, Ayaloglu-Butun F et al (2009) Timing of induction of cardiomyocyte differentiation for in vitro cultured mesenchymal stem cells: a perspective for emergencies. Can J Physiol Pharmacol 87:143–150PubMedCrossRefGoogle Scholar
  58. Tomchuck SL, Zwezdaryk KJ, Coffelt SB (2008) Toll-like receptors on human mesenchymal stem cells drive their migration and immunomodulating responses. Stem Cells 26:99–107PubMedCrossRefGoogle Scholar
  59. Urbanek K, Rota M, Cascapera S et al (2005) Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival. Circ Res 97:663–673PubMedCrossRefGoogle Scholar
  60. Waterman RS, Tomchuck SL, Henkle SL et al (2010) A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an immunosuppressive MSC2 phenotype. PLoS One 5:e10088PubMedCrossRefGoogle Scholar
  61. Weissman IL (2000) Stem cells: units of development, units of regeneration, and units in evolution. Cell 100:157–168PubMedCrossRefGoogle Scholar
  62. Wollert KC, Meyer GP, Lotz J et al (2004) Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 364:141–148PubMedCrossRefGoogle Scholar
  63. Zhao DC, Lei JX, Chen R et al (2005) Bone marrow-derived mesenchymal stem cells protect against experimental liver fibrosis in rats. World J Gastroenterol 11:3431–3440PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Zeynep Tokcaer-Keskin
    • 1
  • Hande Kocak
    • 1
  • Ihsan Gursel
    • 2
  • Kamil C. Akcali
    • 1
  1. 1.Laboratory of Stem Cell Research, Department of Molecular Biology and Genetics, Faculty of Science B-243Bilkent UniversityAnkaraTurkey
  2. 2.Biotherapeutic ODN Research Lab, Department of Molecular Biology and GeneticsBilkent UniversityAnkaraTurkey

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