Mesenchymal Stem Cells: Clinical Applications (An Overview)

Chapter
Part of the Stem Cells and Cancer Stem Cells book series (STEM, volume 6)

Abstract

Mesenchymal stem cells (MSC) based therapy has emerged rapidly over the last decade as a novel tissue repair and regenerative as well as immunomodulatory therapy despite the relative paucity in the knowledge of its exact mechanism of action. Despite that, a growing body of evidence from pre-clinical studies demonstrate that MSC based therapy is safe and efficacious, which has led to the current series of ongoing clinical trials. In this review, the mechanism of action of MSC is discussed and the current clinical trials using MSC and the safety data from early phase 1/2 clinical trials are outlined. After this general discussion, we focus specifically on the use of MSC therapy in peripheral arterial disease from pre-clinical studies to potential use in clinical trials. Finally, we highlight current limitations of MSC based therapy and provide suggestions for a standardised approach to MSC based therapy which permits a more direct comparison with other trials.

Keywords

Amyotrophic Lateral Sclerosis Mesenchymal Stem Cell Peripheral Arterial Disease Graft Versus Host Disease Critical Limb Ischaemia 
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.

References

  1. Barry FP, Murphy JM (2004) Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol 36(4):568–584PubMedCrossRefGoogle Scholar
  2. Dash NR, Dash SN et al (2009) Targeting nonhealing ulcers of lower extremity in human through autologous bone marrow-derived mesenchymal stem cells. Rejuvenation Res 12(5):359–366PubMedCrossRefGoogle Scholar
  3. Duffy GP, Ahsan T et al (2009) Bone marrow-derived mesenchymal stem cells promote angiogenic processes in a time- and dose-dependent manner in vitro. Tissue Eng Part A 15(9):2459–2470PubMedCrossRefGoogle Scholar
  4. Duijvestein M, Vos AC et al (2010) Autologous bone marrow-derived mesenchymal stromal cell treatment for refractory luminal Crohn’s disease: results of a phase I study. Gut 59(12):1662–1669PubMedCrossRefGoogle Scholar
  5. Guiducci S, Porta F et al (2010) Autologous mesenchymal stem cells foster revascularization of ischemic limbs in systemic sclerosis: a case report. Ann Intern Med 153(10):650–654PubMedGoogle Scholar
  6. Hare JM, Traverse JH et al (2009) A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. J Am Coll Cardiol 54(24):2277–2286PubMedCrossRefGoogle Scholar
  7. Huang XP, Sun Z et al (2010) Differentiation of allogeneic mesenchymal stem cells induces immunogenicity and limits their long-term benefits for myocardial repair. Circulation 122(23):2419–2429PubMedCrossRefGoogle Scholar
  8. Jeong JO, Han JW et al (2011) Malignant tumor formation after transplantation of short-term cultured bone marrow mesenchymal stem cells in experimental myocardial infarction and diabetic neuropathy. Circ Res 108(11):1340–1347PubMedCrossRefGoogle Scholar
  9. Kang Y, Park C et al (2010) Unsorted human adipose tissue-derived stem cells promote angiogenesis and myogenesis in murine ischemic hindlimb model. Microvasc Res 80(3):310–316PubMedCrossRefGoogle Scholar
  10. Karussis D, Karageorgiou C et al (2010) Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol 67(10):1187–1194PubMedCrossRefGoogle Scholar
  11. Kebriaei P, Robinson S (2011) Treatment of graft-versus-host-disease with mesenchymal stromal cells. Cytotherapy 13(3):262–268PubMedCrossRefGoogle Scholar
  12. Kim SW, Han H et al (2006) Successful stem cell therapy using umbilical cord blood-derived multipotent stem cells for Buerger’s disease and ischemic limb disease animal model. Stem Cells 24(6):1620–1626PubMedCrossRefGoogle Scholar
  13. Kim Y, Kim H et al (2007) Direct comparison of human mesenchymal stem cells derived from adipose tissues and bone marrow in mediating neovascularization in response to vascular ischemia. Cell Physiol Biochem 20(6):867–876PubMedCrossRefGoogle Scholar
  14. Kinnaird T, Stabile E et al (2004) Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circ Res 94(5):678–685PubMedCrossRefGoogle Scholar
  15. Lasala GP, Silva JA et al (2010) Combination stem cell therapy for the treatment of severe limb ischemia: safety and efficacy analysis. Angiology 61(6):551PubMedCrossRefGoogle Scholar
  16. Laurila JP, Laatikainen L et al (2009) Human embryonic stem cell-derived mesenchymal stromal cell transplantation in a rat hind limb injury model. Cytotherapy 11(6):726–737PubMedCrossRefGoogle Scholar
  17. Lee RH, Pulin AA et al (2009) Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell 5(1):54–63PubMedCrossRefGoogle Scholar
  18. Lee JS, Hong JM et al (2010) A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke. Stem Cells 28(6):1099–1106PubMedCrossRefGoogle Scholar
  19. Lian Q, Zhang Y et al (2010) Functional mesenchymal stem cells derived from human induced pluripotent stem cells attenuate limb ischemia in mice. Circulation 121(9):1113–1123PubMedCrossRefGoogle Scholar
  20. Lu D, Chen B et al (2011) Comparison of bone marrow mesenchymal stem cells with bone marrow-derived mononuclear cells for treatment of diabetic critical limb ischemia and foot ulcer: a double-blind, randomized, controlled trial. Diabetes Res Clin Pract 92(1):26–36PubMedCrossRefGoogle Scholar
  21. Moon MH, Kim SY et al (2006) Human adipose tissue-derived mesenchymal stem cells improve postnatal neovascularization in a mouse model of hindlimb ischemia. Cell Physiol Biochem 17(5–6):279–290PubMedCrossRefGoogle Scholar
  22. Nishishita T, Ouchi K et al (2004) A potential pro-angiogenic cell therapy with human placenta-derived mesenchymal cells. Biochem Biophys Res Commun 325(1):24–31PubMedCrossRefGoogle Scholar
  23. Norgren L, Hiatt WR et al (2007) Inter-society consensus for the management of peripheral arterial disease (TASC II). J Vasc Surg 45(Suppl S):S5–S67PubMedCrossRefGoogle Scholar
  24. Prather WR, Toren A et al (2009) The role of placental-derived adherent stromal cell (PLX-PAD) in the treatment of critical limb ischemia. Cytotherapy 11(4):427–434PubMedCrossRefGoogle Scholar
  25. Rehman J, Traktuev D et al (2004) Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation 109(10):1292–1298PubMedCrossRefGoogle Scholar
  26. Rosova I, Dao M et al (2008) Hypoxic preconditioning results in increased motility and improved therapeutic potential of human mesenchymal stem cells. Stem Cells 26(8):2173–2182PubMedCrossRefGoogle Scholar
  27. Wakitani S, Okabe T et al (2011) Safety of autologous bone marrow-derived mesenchymal stem cell transplantation for cartilage repair in 41 patients with 45 joints followed for up to 11 years and 5 months. J Tissue Eng Regen Med 5(2):146–150PubMedCrossRefGoogle Scholar
  28. Yamout B, Hourani R et al (2010) Bone marrow mesenchymal stem cell transplantation in patients with multiple sclerosis: a pilot study. J Neuroimmunol 227(1–2):185–189PubMedCrossRefGoogle Scholar
  29. Zangi L, Margalit R et al (2009) Direct imaging of immune rejection and memory induction by allogeneic mesenchymal stromal cells. Stem Cells 27(11):2865–2874PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  1. 1.Regenerative Medicine Institute (REMEDI), National Centre for Biomedical Engineering Science (NCBES)National University of Ireland, Galway (NUIG)GalwayIreland

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