Cell Therapy, a New Standard in Management of Chronic Critical Limb Ischemia and Foot Ulcer

Abstract

Fifty percent of diabetics (7% of general population) suffer from peripheral arterial occlusive disease, which may lead to amputation due to critical limb ischemia (CLI). The aim of our study was to prevent major limb amputation (MLA) in this group of patients using a local application of autologous bone marrow stem cells (ABMSC) concentrate. A total of 96 patients with CLI and foot ulcer (FU) were randomized into groups I and II. Patients in group I (n = 42, 36 males, 6 females, 66.2 ± 10.6 years) underwent local treatment with ABMSC while those in group II (n = 54, control, 42 males, 12 females, 64.1 ± 8.6 years) received standard medical care. The frequency of major limb amputation in groups I and II was 21% and 44% within the 120 days of follow up, respectively (p < 0.05). Only in salvaged limbs of group I both toe pressure and toe brachial index increased (from 22.66 ± 5.32 to 25.63 ± 4.75 mmHg and from 0.14 ± 0.03 to 0.17 ± 0.03, respectively, mean ± SEM). The CD34+ cell counts in bone marrow concentrate (BMC) decreased (correlation, p = 0.024) with age, even though there was no correlation between age and healing. An unexpected finding was made of relative, bone marrow lymphopenia in the initial bone marrow concentrates in patients who failed ABMSC therapy (21% of MLA). This difference was statistically significant (p < 0.040). We conclude ABMSC therapy results in 79% limb salvage in patients suffering from CLI and FU. In the remaining 21% lymphopenia and thrombocytopenia were identified as potential causative factors, suggesting that at least a partial correction with platelet supplementation may be beneficial.

Stem Cells in Skin Wound Healing: Are We There Yet?

“…Considering the different number of works using stem cells either injected at the wound borders 15,36 or randomly incorporated within biomaterial-based matrices, [37][38][39][40][41][42] there is skepticism regarding the need for 3D organization. Nonetheless, this discrepancy can be correlated with the limitations of MSC differentiation toward epithelial and endothelial lineages, 43 as well as to the deficient purity/stability of epidermal stem cells cultures.…”

Efficacy of Autologous Bone Marrow Mononuclear Cell Therapy in Patients with Peripheral Arterial Disease

“…Data regarding the TcO2 values after 12 and 48 weeks were reported in only one study and were not appropriate for a meta-analysis 16,29) . Meanwhile, the TcO2 values increased in the six selected trials in the non-RCT group 12,13,[16][17][18]29) after four to eight weeks of cell therapy (MD 11.90, 95% CI 2.37-21. 43, P = 0.01), but not 24 weeks of before and after stem cell treatment in order to assess the effects of therapy in the non-RCT group.…”

Clinical Trials of Adult Stem Cell Therapy for Peripheral Artery Disease

“…[22][23][24][25][26][27][28][29][30][31][32][33] Procedures associated with cell therapy, such as bone marrow aspiration and injection, were generally well-tolerated by the patients, with few adverse events reported. hence, current data is promising, and safety concerns do not outweigh the promise of potential benefit, which must now be tested in definitive clinical trials.…”

“…since that time, numerous other studies have examined the efficacy and safety of cell therapy for Pad, with varying results (tables 1 and 2). [22][23][24][25][26][27][28][29][30][31][32][33] Most clinical trials of cell therapy for Pad have consisted of uncontrolled patient series, with few randomized, properly controlled studies. sample sizes have been relatively small, with most studies enrolling fewer than 50 patients.…”