Autologous Peripheral Blood Mononuclear Cells for Limb Salvage in Diabetic Foot Patients with No-Option Critical Limb Ischemia.

Alessia Scatena,Giorgio Ventoruzzo,Francesco Liistro,Danilo Tacconi,Leonardo Bolognese,Francesca Lucaroni,Leonardo Palombi,Pasquale Petruzzi,Marianna Di Filippi,Nico Attempati,Leonardo Ercolini,Filippo Maioli,Cristina Ambrosone

doi:10.3390/jcm10102213

Abstract

Peripheral blood mononuclear cells (PBMNCs) are reported to prevent major amputation and healing in no-option critical limb ischemia (NO-CLI). The aim of this study is to evaluate PBMNC treatment in comparison to standard treatment in NO-CLI patients with diabetic foot ulcers (DFUs). The study included 76 NO-CLI patients admitted to our centers because of CLI with DFUs. All patients were treated with the same standard care (control group), but 38 patients were also treated with autologous PBMNC implants. Major amputations, overall mortality, and number of healed patients were evaluated as the primary endpoint. Only 4 out 38 amputations (10.5%) were observed in the PBMNC group, while 15 out of 38 amputations (39.5%) were recorded in the control group (p = 0.0037). The Kaplan–Meier curves and the log-rank test results showed a significantly lower amputation rate in the PBMNCs group vs. the control group (p = 0.000). At two years follow-up, nearly 80% of the PBMNCs group was still alive vs. only 20% of the control group (p = 0.000). In the PBMNC group, 33 patients healed (86.6%) while only one patient healed in the control group (p = 0.000). PBMNCs showed a positive clinical outcome at two years follow-up in patients with DFUs and NO-CLI, significantly reducing the amputation rate and improving survival and wound healing. According to our study results, intramuscular and peri-lesional injection of autologous PBMNCs could prevent amputations in NO-CLI diabetic patients.

Highlights

Critical limb ischemia (CLI) has a high incidence in patients with diabetes and is related with high morbidity and mortality rates [1]
The aim of this study is to evaluate Peripheral blood mononuclear cells (PBMNCs) implants in comparison to standard care treatment in no-option critical limb ischemia (NO-CLI) patients with diabetic foot ulcers (DFUs)
In the last few years, a huge number of papers studying the mechanism of action of PBMNCs have been published, both on their characteristic angiogenic potency and on their regenerative and immunomodulatory capacity through the polarization of macrophages [12,43,44]

Summary

Introduction

Critical limb ischemia (CLI) has a high incidence in patients with diabetes and is related with high morbidity and mortality rates [1]. Limb salvage is associated with percutaneous or surgical revascularization, in comparison to the medical treatment in patients with peripheral arterial disease (PAD) and diabetic foot ulcers (DFUs) [2]. Up to 25% of diabetic patients are not eligible for revascularization as a result of the inability to overcome vessel obstruction and/or for critical general conditions [3,4]. No-option critical limb ischemia (NO-CLI) remains a strong unmet clinical need: at 1 year follow-up, NO-CLI diabetic patients showed, respectively, lower rates of limb salvage (13.8% vs 73.4%, p < 0.0001), higher rates of amputation

Objectives

Methods

Results

Discussion

Conclusion