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.

• Keywords
• Amputation, Amputation-free survival, Ischemia, Peripheral artery disease, Stem cell therapy,
• MeSH
• Amputation, Surgical MeSH
• Transplantation, Autologous MeSH
• Cell- and Tissue-Based Therapy * methods   MeSH
• Chronic Limb-Threatening Ischemia * therapy   MeSH
• Ischemia * therapy   MeSH
• Middle Aged MeSH
• Humans MeSH
• Prospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Limb Salvage * methods   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

This current opinion article critically evaluates the efficacy of autologous cell therapy (ACT) for chronic limb-threatening ischemia (CLTI), especially in people with diabetes who are not candidates for standard revascularization. This treatment approach has been used in 'no-option' CLTI in the last two decades and more than 1700 patients have received ACT worldwide. Here we analyze the level of published evidence of ACT as well as our experience with this treatment method. Many studies have shown that ACT is safe and an effective method for patients with the most severe lower limb ischemia. However, some trials did not show any benefit of ACT, and there is some heterogeneity in the types of injected cells, route of administration and assessed endpoints. Nevertheless, we believe that ACT plays an important role in a comprehensive treatment of patients with diabetic foot and severe ischemia.

• MeSH
• Amputation, Surgical MeSH
• Cell- and Tissue-Based Therapy MeSH
• Diabetes Mellitus * MeSH
• Diabetic Foot * therapy   MeSH
• Ischemia etiology   therapy   MeSH
• Humans MeSH
• Retrospective Studies MeSH
• Risk Factors MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: Diabetic patients (DPs) with foot ulcers can receive autologous cell therapy (ACT) as a last therapeutic option. Even DPs who have undergone organ transplantation and are using immunosuppressive (IS) drugs can be treated by ACT. The aim of our study was to analyze the effects of IS drugs on the characteristics of bone marrow-derived stem cells (BM-MSCs). METHODS: The cells were isolated from the bone marrow of DPs, cultivated for 14-18 days, and phenotypically characterized using flow cytometry. These precursor cells were cultured in the presence of various IS drugs. The impact of IS drugs on metabolic activity was measured using a WST-1 assay, and the expression of genes for immunoregulatory molecules was detected through RT-PCR. Cell death was analyzed through the use of flow cytometry, and the production of cytokines was determined by ELISA. RESULTS: The mononuclear fraction of cultured cells contained mesenchymal stem cells (CD45-CD73+CD90+CD105+), myeloid angiogenic cells (CD45+CD146-), and endothelial colony-forming cells (CD45-CD146+). IS drugs inhibited metabolic activity, the expression of genes for immunoregulatory molecules, the production of cytokines, and the viability of the cells. CONCLUSIONS: The results indicate that IS drugs in a dose-dependent manner had a negative impact on the properties of BM-MSCs used to treat ischemic diabetic foot ulcers, and that these drugs could affect the therapeutic potential of BM-MSCs.

• Keywords
• cell-based therapies, diabetes, diabetic foot ulcers, immunosuppressive drugs,
• Publication type
• Journal Article MeSH