Abstract
Treatment options of ischemic vascular disease of the lower limbs are a challenged field that necessitates new therapeutic modalities. Stem cell transplantation offers a promising achievement of therapeutic angiogenesis in patients with ischemic limbs. Our study investigated the efficacy and safety of the implantation of autologous peripheral blood mononuclear cells (PBMNCs) mobilized by granulocyte colony-stimulating factor (G-CSF) in patients with chronic limb ischemia. Twenty-four patients with chronic lower limb ischemia were enrolled and divided randomly into two groups: the implanted group (n = 12) and the control group (n = 12). In the implanted group, the patients received subcutaneous injections of recombinant human G-CSF (300 μg/day) for 5 days to mobilize stem/progenitor cells, and their PBMNCs were harvested using a blood cell separator and were implanted by multiple intramuscular injections into the ischemic limbs, while the control group was injected with sterile saline and received conventional medical treatment. All patients were followed up after 12 weeks. At the end of the follow-up period, the main manifestations significantly improved in patients of the implanted group compared with the control group. The mean of rest pain decreased from the baseline level of 6.42 ± 2.15 to 1.67 ± 0.389 (P < 0.001). The mean of pain-free walking distance increased from 25.00 ± 8.90 to 409.00 ± 104.00 (P < 0.001). The mean ankle–brachial pressure index increased from 0.45 ± 0.12 to 0.79 ± 0.38 (P = 0.005). Seven out of nine limb ulcers and wounds (77.8 %) of implanted patients healed after cell implantation. Two lower limb amputations (16.67 %) occurred in the implanted patients. In contrast, eight control patients (66.67 %) had to receive lower limb amputation. Implantation of stem/progenitor cells is a feasible and readily available effective strategy for therapeutic angiogenesis in patients with chronic limb ischemia.
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References
Balkwill F (2003) Chemokine biology in cancer. Semin Immunol 15:49–55
Collinson DJ, Donnelly R (2004) Therapeutic angiogenesis in peripheral arterial disease: can biotechnology produce an effective collateral circulation? Eur J Vasc Endovasc Surg 28(1):9–23
Higashi Y, Kimura M, Hara K et al (2004) 2004 Autologous bone marrow mononuclear cell implantation improves endothelium-dependent vasodilation in patients with limb ischemia. Circulation 109:1215–1218
Huang PP, Li SZ, Han MZ et al (2004) Autologous transplantation of peripheral blood stem cells as an effective therapeutic approach for severe arteriosclerosis obliterans of lower extremities. Thromb Haemost 91:606–609
Huang P, Li S, Han M, Xiao Z, Yang R, Han ZC (2005) Autologous transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes. Diabetes Care 28:2155–2160
Huang PP, Yang XF, Li SZ, Wen JC, Zhang Y, Han ZC (2007) Randomised comparison of G-CSF-mobilized peripheral blood mononuclear cells versus bone marrow mononuclear cells for the treatment of patients with lower limb arteriosclerosis obliterans. Thromb Haemost 98:1335–1342
Ishida A, Ohya Y, Sakuda H, Ohshiro K, Higashiuesato Y, Nakaema M, Matsubara S, Yakabi S, Kakihana A, Ueda M, Miyagi C, Yamane N, Koja K, Komori K, Takishita S (2005) Autologous peripheral blood mononuclear cell implantation for patients with peripheral arterial disease improves limb ischemia. Circ J 69:1260–1265
Kim SW, Han H, Chae GT, Lee SH, Bo S, Yoon JH, Lee YS, Lee KS, Park HK, Kang KS (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):1620–1626
Koshikawa M, Shimodaira S, Yoshioka T et al (2006) Therapeutic angiogenesis by bone marrow implantation for critical hand ischemia in patients with peripheral arterial disease: a pilot study. Curr Med Res Opin 22:793–798
Mantovani A, Sozzani S, Locati M et al (2002) Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 23:549–555
Murasawa S, Asahara T (2005) Endothelial progenitor cells for vasculogenesis. Physiology 20:36–42
Sica A, Bronte V (2007) Altered macrophage differentiation and immune dysfunction in tumor development. J Clin Investig 117:1155–1166
Sica A, Schioppa T, Mantovani A, Allavena P (2006) Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer 42:717–727
Tateishi-Yuyama E, Matsubara H, Murohara T, Ikeda U, Shintani S, Masaki H, Amano K, Kishimoto Y, Yoshimoto K, Akashi H, Shimada K, Iwasaka T, Imaizumi T (2002) Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomized controlled trial. Lancet 360:427–435
Zampetaki A, Kirton JP, Xu Q (2008) Vascular repair by endothelial progenitor cells. Cardiovasc Res 78(3):413–421
Zhou B, Ma XF, Liu PX, Fang ZH, Wang SL, Han ZB, Poon M, Han ZC (2010) Therapeutic vasculogenesis by transplantation of oxLDL-treated endothelial progenitor cells. J Lipid Res 21:102–110
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This study was supported in part by grants from Beni Suef Hospital. We thank our patients for their willing participation in our research.
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El Ansary, M., AlAbden, A.Z., Halim, A.A. et al. Stem cell implantation in the treatment of peripheral vascular disease. Comp Clin Pathol 23, 169–173 (2014). https://doi.org/10.1007/s00580-012-1590-7
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DOI: https://doi.org/10.1007/s00580-012-1590-7