Exp Clin Endocrinol Diabetes 2013; 121(01): 48-53
DOI: 10.1055/s-0032-1311646
Article
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Therapeutic Outcomes of Transplanting Autologous Granulocyte Colony-stimulating Factor-mobilised Peripheral Mononuclear Cells in Diabetic Patients with Critical Limb Ischaemia

L. Mohammadzadeh
1   Tehran University of Medical Sciences, Rasul Akram Hospital, Tehran, Islamic Republic of Iran
,
S. H. Samedanifard
1   Tehran University of Medical Sciences, Rasul Akram Hospital, Tehran, Islamic Republic of Iran
,
A. Keshavarzi
1   Tehran University of Medical Sciences, Rasul Akram Hospital, Tehran, Islamic Republic of Iran
,
K. Alimoghaddam
1   Tehran University of Medical Sciences, Rasul Akram Hospital, Tehran, Islamic Republic of Iran
,
B. Larijani
1   Tehran University of Medical Sciences, Rasul Akram Hospital, Tehran, Islamic Republic of Iran
,
A. Ghavamzadeh
1   Tehran University of Medical Sciences, Rasul Akram Hospital, Tehran, Islamic Republic of Iran
,
A. S. Ahmadi
1   Tehran University of Medical Sciences, Rasul Akram Hospital, Tehran, Islamic Republic of Iran
,
A. Shojaeifard
1   Tehran University of Medical Sciences, Rasul Akram Hospital, Tehran, Islamic Republic of Iran
,
M. R. Ostadali
2   Tehran University of Medical Sciences, Endocrinology and Metabolism Research Centre, Tehran, Islamic Republic of Iran
,
A. M. Sharifi
4   Tehran University of Medical Sciences, Cellular and Molecular Research Centre, Tehran, Iran
,
M. R. Amini
2   Tehran University of Medical Sciences, Endocrinology and Metabolism Research Centre, Tehran, Islamic Republic of Iran
,
A. Mahmoudian
3   Department of Microbiology and Immunology, The University of ­Melbourne, Parkville, Victoria, Australia
,
H. Fakhraei
2   Tehran University of Medical Sciences, Endocrinology and Metabolism Research Centre, Tehran, Islamic Republic of Iran
,
M. Aalaa
2   Tehran University of Medical Sciences, Endocrinology and Metabolism Research Centre, Tehran, Islamic Republic of Iran
,
M. R. Mohajeri-Tehrani
2   Tehran University of Medical Sciences, Endocrinology and Metabolism Research Centre, Tehran, Islamic Republic of Iran
› Author Affiliations
Further Information

Publication History

received 11 June 2011
first decision 09 April 2012

accepted 10 April 2012

Publication Date:
17 January 2013 (online)

Abstract

The efficacy and safety of transplanting autologous mesenchymal stem cells (MSCs), from granulocyte-colony-stimulating factor (G-CSF)-mobilised peri­pheral blood, was investigated in diabetic patients with critical limb ischaemia (CLI).

After 3 months, the transplanted group of patients (n=7) showed a significant improvement in ischaemia manifestations, including pain and neurological signs, wound healing and the rate of lower-limb amputation, compared to the control group of patients (n=14). Pain was significantly reduced in the transplanted group compared to controls (P=0.014). The ankle-brachial index (ABI) and the pulse strength within ischaemic tissues of the transplanted group were significantly improved (P=0.035 and P=0.01, respectively).

Importantly, 50% of the control group (7/14 patients) faced major amputation of a limb at the study’s conclusion, compared to none of 7 patients in the transplanted group (P=0.047).The safety of transplantation was confirmed by observing no adverse reactions among the transplanted group, including infection and immunological rejection.

Hence, this study provides further evidence that transplantation of autologous peripheral blood MSCs, mobilised by G-CSF, induces angiogenesis and improves the wound healing process in diabetic patients with CLI.

 
  • References

  • 1 Barcelos LS, Duplaa C, Kränkel N et al. Human CD133+ progenitor cells promote the healing of diabetic ischemic ulcers by paracrine stimulation of angiogenesis and activation of Wnt signaling. Circ Res 2009; 104: 1095-1102
  • 2 Battiwalla M, Hematti P. Mesenchymal stem cells in hematopoietic stem cell transplantation. Cytotherapy 2009; 11: 503-515
  • 3 Burt RK, Testori A, Oyama Y et al. Autologous peripheral blood CD133+ cell implantation for limb salvage in patients with critical limb ischemia. Bone Marrow Transplant 2010; 45: 111-116
  • 4 Cho HJ, Kim HS, Lee MM et al. Mobilized endothelial progenitor cells by granulocyte-macrophage colony-stimulating factor accelerate reendothelialization and reduce vascular inflammation after intravascular radiation. Circulation 2003; 108: 2918-2925
  • 5 de Win MM, Theuvenet WJ, Roche PW et al. The paper grip test for screening on intrinsic muscle paralysis in the foot of leprosy patients. Int J Lepr Other Mycobact Dis 2002; 70: 16-24
  • 6 Duh E, Aiello LP. Vascular endothelial growth factor and diabetes: the agonist versus antagonist paradox. Diabetes 1999; 48: 1899-1906
  • 7 Fadini GP, Avogaro A. Autologous transplantation of granulocyte colony-stimulating factor- mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes. Diabetes Care 2006; 29: 478-479 author reply 479-480
  • 8 Hicks ML, Lonial S, Langston A et al. Optimizing the timing of chemotherapy for mobilizing autologous blood hematopoietic progenitor cells. Transfusion 2007; 47: 629-635
  • 9 Huang P, Li S, Han M et al. Autologous transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes. Diabetes Care 2005; 28: 2155-2160
  • 10 Iba O, Matsubara H, Nozawa Y et al. Angiogenesis by implantation of peripheral blood mononuclear cells and platelets into ischemic limbs. Circulation 2002; 106: 2019-2025
  • 11 Ishida A, Ohya Y, Sakuda H et al. Autologous peripheral blood mononuclear cell implantation for patients with peripheral arterial disease improves limb ischemia. Circ J 2005; 69: 1260-1265
  • 12 Ishikawa M, Asahara T. Endothelial progenitor cell culture for vascular regeneration. Stem Cells Dev 2004; 13: 344-349
  • 13 Jackson KA, Majka SM, Wang H et al. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 2001; 107: 1395-1402
  • 14 Kajiguchi M, Kondo T, Izawa H et al. Safety and efficacy of autologous progenitor cell transplantation for therapeutic angiogenesis in patients with critical limb ischemia. Circ J 2007; 71: 196-201
  • 15 Kienstra KA, Jackson KA, Hirschi KK. Injury mechanism dictates contribution of bone marrow-derived cells to murine hepatic vascular regeneration. Pediatr Res 2008; 63: 131-136
  • 16 Kwon DS, Gao X, Liu YB et al. Treatment with bone marrow-derived stromal cells accelerates wound healing in diabetic rats. Int Wound J 2008; 5: 453-463
  • 17 Lechner A, Habener JF. Stem/progenitor cells derived from adult tissues: potential for the treatment of diabetes mellitus. Am J Physiol Endocrinol Metab 2003; 284: E259-E266
  • 18 Loomans CJ, de Koning EJ, Staal FJ et al. Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes 2004; 53: 195-199
  • 19 Minamino K, Adachi Y, Okigaki M et al. Macrophage colony-stimulating factor (M-CSF), as well as granulocyte colony-stimulating factor (G-CSF), accelerates neovascularization. Stem Cells 2005; 23: 347-354
  • 20 Ono K, Tsuchida A, Kawai H et al. Ankle-brachial blood pressure index predicts all-cause and cardiovascular mortality in hemodialysis patients. J Am Soc Nephrol 2003; 14: 1591-1598
  • 21 Dorros G, Jaff MR, Dorros AM et al. Tibioperoneal (outflow lesion) angioplasty can be used as primary treatment in 235 patients with critical limb ischemia: five-year follow-up. Circulation 2001; 104: 2057-2062
  • 22 Oyibo SO, Jude EB, Tarawneh I et al. A comparison of two diabetic foot ulcer classification systems: the Wagner and the University of Texas wound classification systems. Diabetes Care 2001; 24: 84-88
  • 23 Seiler C, Pohl T, Wustmann K et al. Promotion of collateral growth by granulocyte-macrophage colony-stimulating factor in patients with coronary artery disease: a randomized, double-blind, placebo-controlled study. Circulation 2001; 104: 2012-2017
  • 24 Tateishi-Yuyama E, Matsubara H, Murohara T et al. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet 2002; 360: 427-435
  • 25 Tepper OM, Galiano RD, Capla JM et al. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation 2002; 106: 2781-2786
  • 26 Wang Y, Tägil K, Ripa RS et al. Effect of mobilization of bone marrow stem cells by granulocyte colony stimulating factor on clinical symptoms, left ventricular perfusion and function in patients with severe chronic ischemic heart disease. Int J Cardiol 2005; 100: 477-483
  • 27 Yang XF, Wu YX, Wang HM et al. Autologous peripheral blood stem cells transplantation in treatment of 62 cases of lower extremity ischemic disorder. Zhonghua Nei Ke Za Zhi 2005; 44: 95-98
  • 28 Zafarghandi MR, Ravari H, Aghdami N et al. Safety and efficacy of granulocyte-colony-stimulating factor administration following autologous intramuscular implantation of bone marrow mononuclear cells: a randomized controlled trial in patients with advanced lower limb ischemia. Cytotherapy 2010; 12: 783-791