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.

1st Faculty of Medicine Charles University Prague Czech Republic

Department of Data Science Institute for Clinical and Experimental Medicine Prague Czech Republic

Diabetes Center Tameside and Glossop Integrated Care NHS Foundation Trust Ashton under Lyne and University of Manchester Manchester UK

Diabetes Centre Institute for Clinical and Experimental Medicine Prague Czech Republic

Transplantation Surgery Department Institute for Clinical and Experimental Medicine Prague Czech Republic

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