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Stem cell therapy for critical limb ischaemia — a review

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Abstract

Critical limb ischaemia is an intractable condition associated with high levels of amputation, leading to a low quality of life and increased morbidity and mortality. It is often not treatable by standard therapeutic modalities. Neoangiogenesis has been proposed as a novel method of treatment of such patients. Vascular endothelial growth factor (VEGF) and cytokine fibroblast growth factor (FGF-1) have been shown to elicit neoangiogenesis. Stem cells are progenitor cells which can differentiate in vivo into different types of cells. Mesenchymal stem cells (MSCs) are a type of adult stem cells which have an immunomodulatory effect. Stem cell therapy has been used in animal studies to improve limb vascularity in rat and rabbit models. Several clinical studies have also validated their use for critical limb ischaemia. However many issues are still unresolved. These include the dosage, delivery and safety issues in relation to stem cell therapy. However stem cells are likely to be an important therapeutic modality to treat critical limb ischaemia in the near future.

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References

  1. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG (2007) Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). Eur J Vasc Endovasc Surg 33:S1–S75

    Article  PubMed  Google Scholar 

  2. Hirsch AT, Criqui MH, Treat-Jacobson D, et al. (2001) Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA 286:1317–1324

    Article  PubMed  CAS  Google Scholar 

  3. Anon (1996) Critical Limb Ischaemia: management and outcome: Report of a National Survey: The Vascular Society of Great Britain and Ireland. Eur J Endovac Surg 12: 131–135

  4. Anon (2005) Lower extremity disease among persons aged > or=40 years with and without diabetes—United States, 1999–2002. Centers for Disease Control and Prevention (CDC). MMWR Morb Mortal Wkly Rep 54: 1158–1160

    Google Scholar 

  5. Dormandy JA, Rutherford RB (2000) Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Consensus (TASC). J Vasc Surg 31:S1–S296

    Article  PubMed  CAS  Google Scholar 

  6. Albers M, Fratezi AC, De LN (1992) Assessment of quality of life of patients with severe ischaemia as a result of infrainguinal arterial occlusive disease. J Vasc Surg 6:54–59

    Google Scholar 

  7. Dormandy J, Heeck L, Vig S (1999) Predicting which patients will develop chronic critical leg ischaemia. Semin Vasc Surg 12:138–141

    PubMed  CAS  Google Scholar 

  8. Schainfeld RM, Isner JM (1999) Critical limb ischaemia: nothing to give at the office? Ann Intern Med 130:442–444

    PubMed  CAS  Google Scholar 

  9. Milkiewicz M, Pugh CW, Egginton S (2004) Inhibition of endogenous HIF inactivation induces angiogenesis in ischaemic skeletal muscles of mice. J Physiol 560:21–26

    Article  PubMed  CAS  Google Scholar 

  10. El Oakley RM, Seow KK, Tang TP, Kok CW, Teh M, Lim YT, Lim SK (2002) Whole bone marrow transplantation induces angiogenesis following acute ischaemia. Redox Rep 7:215–218

    Article  PubMed  Google Scholar 

  11. Asahara T, Murohara T, Sullivan A, et al. (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967

    Article  PubMed  CAS  Google Scholar 

  12. Ippokratis P, Giannoudis P V (2005) Biology of mesenchymal stem cells injury. Int J Care Injured 36S:S8–S12

    Google Scholar 

  13. Gerwins P, Skoldenberg E, Claesson-Welsh L (2000) Function of fibroblast growth factors and vascular endothelial growth factors and their receptors in angiogenesis. Crit Rev Oncol Hematol 34:185–194

    Article  PubMed  CAS  Google Scholar 

  14. Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186

    PubMed  CAS  Google Scholar 

  15. Pu LQ, Sniderman AD, Brassard R, Lachapelle KJ, Graham AM, Lisbona R, Symes JF (1993) Enhanced revascularization of the ischemic limb by angiogenic therapy. Circulation 88:208–215

    PubMed  CAS  Google Scholar 

  16. van Weel V, Deckers MM, Grimbergen JM, van Leuven KJ, Lardenoye JH, Schlingemann RO, van Nieuw Amerongen GP, van Bockel JH, van Hinsbergh VW, Quax PH (2004) Vascular endothelial growth factor overexpression in ischemic skeletal muscle enhances myoglobin expression in vivo. Circ Res 95:58–66

    Article  PubMed  Google Scholar 

  17. McDonnell K, Bowden ET, Cabal-Manzano R, Hoxter B, Riegel AT, Wellstein A (2005) Vascular leakage in chick embryos after expression of a secreted binding protein for fibroblast growth factors. Lab Invest 85:747–755

    Article  PubMed  CAS  Google Scholar 

  18. Hirata K, Li Tao-Shang, Nishida M, Ito H, Matsuzaki M, Kasaoka S, Harmano K (2003) Autologous bone marrow cell implantation as therapeutic angiogenesis for ischemic hindlimb in diabetic rat model. Am J Heart Care Physiol 284:66–70

    Google Scholar 

  19. Tateishi-Yuyama E, Matsubara H, Murohara T, Ikeda U, Shintani S, Masaki H, Amano K, Kishimoto Y, Yoshimoto K, Akashi H (2002) Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bonemarrow cells: a pilot study and a randomised controlled trial. Lancet 360:427–435

    Article  PubMed  Google Scholar 

  20. Sprengers RW, Lips DL, Moll FL, Verhaar MC (2008) Progenitor cell therapy in patients with critical limb ischaemia without surgical options. Ann Surg 247:411–420

    Article  PubMed  Google Scholar 

  21. Shibata T, Naruse K, Kamiya H, Kozakae M, Kondo M, Yasuda Y, Nakamura N, Ota K, Tosaki T, Matsuki T, et al. (2008) Transplantation of bone marrow-derived mesenchymal stem cells improves diabetic polyneuropathy in rats diabetes 57(11):3099–3107

    CAS  Google Scholar 

  22. Waters RE, Terjung RL, Peters KG, Annex BH (2004) Preclinical models of human peripheral arterial occlusive disease: implications for investigation of therapeutic agents. J Appl Physiol 97(2):773–780

    Article  PubMed  CAS  Google Scholar 

  23. Hori Y, Gu X, Xie X, Kim SK (2005) Differentiation of insulin-producing cells from human neural progenitor cells. PLoS Med 2:e103

    Article  PubMed  Google Scholar 

  24. Kajiguchi M, Kondo T, Izawa H, Kobayashi M, Yamamoto K, Shintani S, Numaguchi Y, Naoe T, Takamatsu J, Komori K, Murohara T (2007) Safety and efficacy of autologous progenitor cell transplantation for therapeutic angiogenesis in patients with critical limb ischaemia. Circ J 71:196–201

    Article  PubMed  Google Scholar 

  25. Lenk K, Adams V, Lurz P, Erbs S, Linke A, Gielen S, Schmidt A, Scheinert D, Biamino G, Emmrich F, Schuler G, Hambrecht R (2005) Therapeutical potential of bloodderived progenitor cells in patients with peripheral arterial occlusive disease and critical limb ischaemia. Eur Heart J 26:1903–1909

    Article  PubMed  Google Scholar 

  26. Bartsch T, Brehm M, Zeus T, et al. (2006) Autologous mononuclear stem cell transplantation in patients with peripheral occlusive arterial disease. Cardiovasc Nurs 21:430–432

    Google Scholar 

  27. Bartsch T, Brehm M, Zeus T, Kögler G, Wernet P, Strauer BE (2007) Transplantation of autologous mononuclear bone marrow stem cells in patients with peripheral arterial disease (The TAM-PAD study). Clin Res Cardiol 96(12):891–899

    Article  PubMed  CAS  Google Scholar 

  28. Kim D-I, Kim M-J, Joh J-H, Shin S-W, Do Y-S, Moon JY, Kim N-R, Lim J-E, Kim A-K, Eo H-S, Kim B-S, Cho S-W, Yang S-H, Park C-J, Shim J-S (2006) Angiogenesis facilitated by autologous whole bone marrow stem cell transplantation for Buerger’s disease. Stem Cells 24: 1194–1200

    Article  PubMed  Google Scholar 

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  1. Stempeutics Research, Kuala Lumpur, Malaysia

    Anjan Kumar Das

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  1. Anjan Kumar Das
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Correspondence to Anjan Kumar Das.

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Das, A.K. Stem cell therapy for critical limb ischaemia — a review. Indian J Surg 71, 177–181 (2009). https://doi.org/10.1007/s12262-009-0059-7

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  • DOI: https://doi.org/10.1007/s12262-009-0059-7

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