Clinical Evaluation of Human Umbilical Cord Mesenchymal Stem Cell Transplantation After Angioplasty for Diabetic Foot^[*]

Abstract

Aims: The multilineage differentiation potential of human umbilical cord mesenchymal stem cells (HUCMSCs) holds therapeutic promise for non-healing ulcers and tissue regeneration. The present study evaluated the effects of HUCMSC transplantation after angioplasty for treatment of diabetic foot.

Methods: Included in the study were 53 patients (72 limbs) with severe symptoms of Fontaine II-IV diabetic foot accompanied by varying degrees of lower extremity arterial disease. The patients were randomly apportioned to a control group (25 patients; 38 limbs) or an experimental group (28 patients; 34 limbs). Patients of both groups received interventional treatment with angioplasty; those in the experimental group also received HUCMSCs by endovascular infusion and injection around the foot ulcer.

Results: Within the 3-month follow-up, relative to patients in the control group, those in the experimental group experienced significantly greater and more stable improvements in skin temperature, ankle-brachial pressure index, transcutaneous oxygen tension, and claudication distance. Notably, 3 months after treatment a significant increase in neovessels, accompanied by complete or gradual ulcer healing, was shown in the experimental group. In addition, no serious complications or adverse reactions were associated with the treatment.

Conclusion: Therefore, our results indicate that HUCMSC transplantation after angioplasty is a safe and effective clinical therapy for severe diabetic foot.

Key words

diabetic foot - angioplasty - human umbilical cord mesenchymal stem cells - transplantation

^* Time and setting: This study was conducted at the Department of Interventional Radiology and Department of Endocrinology, First People’s Hospital of Hefei City and the Blood Center of Anhui Province from April 2011 to December 2013

• References

• 1 Morbach S, Muller E, Reike H et al. Diabetic foot syndrome. Exp Clin Endocrinol Diabetes 2014; 122: 416-424
• 2 Apelqvist J, Bakker K, van Houtum WH et al. Practical guidelines on the management and prevention of the diabetic foot: based upon the International Consensus on the Diabetic Foot (2007) Prepared by the International Working Group on the Diabetic Foot. Diabetes Metab Res Rev 2008; 24 (Suppl. 01) S181-S187
• 3 Fang C, Li M, Cheng Y. Clinical effect and necessity of interventional treatment in diabetic foot before and after amputation. Jieru Fangshe Xue Zazhi 2006; 15: 390-392
• 4 Liu C, Shao J, Liu B et al. [A clinical study of infrapopliteal balloon angioplasty for patients with critical lower limb ischemia]. Zhonghua wai ke za zhi [Chinese journal of surgery] 2010; 48: 253-256
• 5 Lee SH, Lee JH, Cho KH. Effects of Human Adipose-derived Stem Cells on Cutaneous Wound Healing in Nude Mice. Ann Dermatol 2011; 23: 150-155
• 6 Akita S, Yoshimoto H, Akino K et al. Early experiences with stem cells in treating chronic wounds. Clin Plast Surg 2012; 39: 281-292
• 7 Tang J, Xie Q, Pan G et al. Mesenchymal stem cells participate in angiogenesis and improve heart function in rat model of myocardial ischemia with reperfusion. Eur J Cardiothorac Surg 2006; 30: 353-361
• 8 Honma T, Honmou O, Iihoshi S et al. Intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat. Exp Neurol 2006; 199: 56-66
• 9 Al-Khaldi A, Al-Sabti H, Galipeau J et al. Therapeutic angiogenesis using autologous bone marrow stromal cells: improved blood flow in a chronic limb ischemia model. Ann Thorac Surg 2003; 75: 204-209
• 10 Malgieri A, Kantzari E, Patrizi MP et al. Bone marrow and umbilical cord blood human mesenchymal stem cells: state of the art. Int J Clin Exp Med 2010; 3: 248-269
• 11 Rogers I, Casper RF. Umbilical cord blood stem cells. Best Pract Res Clin Obstet Gynaecol 2004; 18: 893-908
• 12 Liu Z, Li S, Yang H et al. Study of mesenchymal stem cells from the human umbilical cord induced into osteoblasts in vitro. Chinese Journal of Blood Transfusion 2011; 5: 008
• 13 Sumpio BE, Lee T, Blume PA. Vascular evaluation and arterial reconstruction of the diabetic foot. Clin Podiatr Med Surg 2003; 20: 689-708
• 14 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
• 15 Adam DJ, Beard JD, Cleveland T et al. Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomised controlled trial. Lancet 2005; 366: 1925-1934
• 16 Li S, Jiang G, Zhao J. Inferior knee arterial endoluminal angioplasty in treating severe lower limb ischemia though the DEEP balloon catheter. Jieru Fangshe Xue Zazhi 2008; 17: 858-861
• 17 Schillinger M, Sabeti S, Loewe C et al. Balloon angioplasty versus implantation of nitinol stents in the superficial femoral artery. N Engl J Med 2006; 354: 1879-1888
• 18 Ziegelhoeffer T, Fernandez B, Kostin S et al. Bone marrow-derived cells do not incorporate into the adult growing vasculature. Circ Res 2004; 94: 230-238
• 19 Scheinert D, Ulrich M, Scheinert S et al. Comparison of sirolimus-eluting vs. bare-metal stents for the treatment of infrapopliteal obstructions. EuroIntervention 2006; 2: 169-174
• 20 Carbayo JA, Divison JA, Escribano J et al. Using ankle-brachial index to detect peripheral arterial disease: prevalence and associated risk factors in a random population sample. Nutr Metab Cardiovasc Dis 2007; 17: 41-49
• 21 Aquino R, Johnnides C, Makaroun M et al. Natural history of claudication: long-term serial follow-up study of 1244 claudicants. J Vasc Surg 2001; 34: 962-970
• 22 Pearson TA. New tools for coronary risk assessment: what are their advantages and limitations?. Circulation 2002; 105: 886-892
• 23 Rossi M, Carpi A. Skin microcirculation in peripheral arterial obliterative disease. Biomed Pharmacother 2004; 58: 427-431
• 24 Faglia E, Dalla Paola L, Clerici G et al. Peripheral angioplasty as the first-choice revascularization procedure in diabetic patients with critical limb ischemia: prospective study of 993 consecutive patients hospitalized and followed between 1999 and 2003. Eur J Vasc Endovasc Surg 2005; 29: 620-627
• 25 Sen HM, Sen H, Asik M et al. The importance of education in diabetic foot care of patients with diabetic neuropathy. Exp Clin Endocrinol Diabetes 2015; 123: 178-181
• 26 Heyden A, Ionescu MC, Romorini S et al. Hippocampal enlargement in Bassoon-mutant mice is associated with enhanced neurogenesis, reduced apoptosis, and abnormal BDNF levels. Cell Tissue Res 2011; 346: 11-26