AIMS: Data about long-term clinical outcomes of revascularization procedures, especially for autologous cell therapy (ACT), in diabetic patients with chronic limb-threatening ischaemia (CLTI) are lacking. The aim of our study was to compare the mortality and amputation rates in patients with diabetic foot ulcers (DFU) and CLTI treated by ACT with patients treated by repeated percutaneous transluminal angioplasty (re-PTA) and those treated conservatively. MATERIALS AND METHODS: One-hundred and thirty patients with DFU and CLTI (defined as transcutaneous oxygen pressure-TcPO2 <30 mmHg after unsuccessful standard revascularization) treated in our foot clinic over 9 years were enrolled in the study. Forty-five patients were treated by ACT, 43 patients underwent re-PTA, and 42 patients were treated conservatively and formed the control group. Overall survival, amputation-free survival (AFS) and major amputation rate were assessed over a 7-year follow-up period. RESULTS: Baseline demographic characteristics and comorbidities were similar between groups. However, patients in ACT and control groups had significantly worse baseline angiograms in accordance with Graziani and GLASS (infrapopliteal region) classifications than the re-PTA group (both p < 0.001), but there were no differences in baseline values of TcPO2 between groups. AFS in the ACT and re-PTA groups were significantly longer compared to control (both p < 0.001). The rate of major amputation was significantly lower in both active groups (both p < 0.001). The re-PTA group showed significantly longer overall survival compared to the control group (p < 0.001), but there was no significant difference between ACT and control groups (p = 0.063) and ACT and re-PTA groups (p = 0.081) in this parameter. CONCLUSIONS: Our study showed significantly longer AFS and lower major amputation rates in patients treated by ACT and re-PTA in contrast to patients treated conservatively. Overall survival was significantly longer only in the re-PTA group. ACT was shown to be effective in long-term limb salvage in people with no-option CLTI.

• Klíčová slova
• cellular research, clinical trial, diabetes complications, effectiveness,
• MeSH
• amputace statistika a číselné údaje   MeSH
• angioplastika * MeSH
• autologní transplantace MeSH
• buněčná a tkáňová terapie * MeSH
• chronická kritická ischemie končetin * terapie   mortalita   MeSH
• diabetická noha * terapie   mortalita   komplikace   chirurgie   MeSH
• ischemie * terapie   mortalita   MeSH
• konzervativní terapie * MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• výsledek terapie MeSH
• záchrana končetiny statistika a číselné údaje   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

BACKGROUNDS: Autologous cell therapy (ACT) could be a treatment option for patients with chronic limb-threatening ischemia (CLTI) when standard vascular intervention is impossible. This study aimed to analyze risk factors affecting therapeutic success and identify patients with diabetes most responsive to ACT. METHODS: In this prospective study, 129 treatments were provided to 118 limbs in 107 no-option CLTI patients with diabetes. Bone marrow was obtained, and stem cells were processed and injected into the calf muscles of the affected limb. After 16 years, we analyzed the influence of baseline factors related to patients (diabetes parameters, comorbidities, medications), limb ischemia (TcPO2 value, Graziani and GLASS classifications), ulcer (descriptions according to Wagner, WIfI, SINBAD and Texas classifications), and infection (the value of CRP, the presence of the osteomyelitis, resistant bacteria and clinical signs of infections). Outcomes were limb salvage (LS) and amputation-free survival (AFS), which were assessed using Cox regression models. RESULTS: Major amputation was performed in 41 out of 118 limbs (31.8%). The use of immunosuppressive therapy (HR 2.48, CI 1.30-4.73), higher stages of GLASS FP (femoropopliteal) score (HR 1.58, CI 1.31-1.90) in the univariate model, and signs of clinical infection (HR 2.21, CI 1.01-4.839) in the multivariable model significantly impacted LS. Shorter AFS was associated with a higher GLASS FP score (HR 1.28, CI 1.13-1.46), dialysis (HR 2.05, CI 1.33 - 3.16 ), hypoalbuminemia (HR 0.93, CI 0.89-0.98), signs of clinical infection (HR 1.99, CI 1.26-3.15) in the univariable model, and immunosuppression (HR 2.31, CI 1.09-4.95) in the multivariable model. CONCLUSION: Decisions to manage patients with no-option CLTI should be based on involvement of the peripheral circulation, the presence of infection and co-morbidities. Those with minimal impairment of the FP segment, with the best possible nutritional status and without signs of infection would benefit the most. Furthermore, we should be careful with dialysis patients and those on immunosuppressive therapy.

• Klíčová slova
• Amputation, Amputation-free survival, Ischemia, Peripheral artery disease, Stem cell therapy,
• MeSH
• amputace MeSH
• autologní transplantace MeSH
• buněčná a tkáňová terapie * metody   MeSH
• chronická kritická ischemie končetin * terapie   MeSH
• ischemie * terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• záchrana končetiny * metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Autologous cell therapy (ACT) is primarily used in diabetic patients with chronic limb-threatening ischemia (CLTI) who are not candidates for standard revascularization. According to current research, this therapy has been shown in some studies to be effective in improving ischemia parameters, decreasing the major amputation rate, and in foot ulcer healing. This review critically evaluates the efficacy of ACT in patients with no-option CLTI, discusses the use of mononuclear and mesenchymal stem cells, and compares the route of delivery of ACT. In addition to ACT, we also describe the use of new revascularization strategies, e.g., nanodiscs, microbeads, and epigenetics, that could enhance the therapeutic effect. The main aim is to summarize new findings on subcellular and molecular levels with the clinical aspects of ACT.

• Klíčová slova
• chronic limb-threatening ischemia, peripheral artery disease, stem cell therapy,
• MeSH
• autologní transplantace * MeSH
• buněčná a tkáňová terapie metody   MeSH
• chronická kritická ischemie končetin terapie   MeSH
• diabetes mellitus terapie   MeSH
• ischemie terapie   MeSH
• lidé MeSH
• transplantace mezenchymálních kmenových buněk metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH