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.
- 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
AIMS/HYPOTHESIS: The aim of this substudy (Eudra CT No:2019-001997-27)was to assess ATB availability in patients with infected diabetic foot ulcers(IDFUs)in the context of microcirculation and macrocirculation status. METHODS: For this substudy, we enrolled 23 patients with IDFU. Patients were treated with boluses of amoxicillin/clavulanic acid(AMC)(12patients) or ceftazidime(CTZ)(11patients). After induction of a steady ATB state, microdialysis was performed near the IDFU. Tissue fluid samples from the foot and blood samples from peripheral blood were taken within 6 hours. ATB potential efficacy was assessed by evaluating the maximum serum and tissue ATB concentrations(Cmax and Cmax-tissue)and the percentage of time the unbound drug tissue concentration exceeds the minimum inhibitory concentration (MIC)(≥100% tissue and ≥50%/60% tissue fT>MIC). Vascular status was assessed by triplex ultrasound, ankle-brachial and toe-brachial index tests, occlusive plethysmography comprising two arterial flow phases, and transcutaneous oxygen pressure(TcPO2). RESULTS: Following bolus administration, the Cmax of AMC was 91.8 ± 52.5 μgmL-1 and the Cmax-tissue of AMC was 7.25 ± 4.5 μgmL-1(P<0.001). The Cmax for CTZ was 186.8 ± 44.1 μgmL-1 and the Cmax-tissue of CTZ was 18.6 ± 7.4 μgmL-1(P<0.0001). Additionally, 67% of patients treated with AMC and 55% of those treated with CTZ achieved tissue fT>MIC levels exceeding 50% and 60%, respectively. We observed positive correlations between both Cmax-tissue and AUCtissue and arterial flow. Specifically, the correlation coefficient for the first phase was r=0.42; (P=0.045), and for the second phase, it was r=0.55(P=0.01)and r=0.5(P=0.021). CONCLUSIONS: Bactericidal activity proved satisfactory in only half to two-thirds of patients with IDFUs, an outcome that appears to correlate primarily with arterial flow.
- MeSH
- antibakteriální látky * farmakokinetika aplikace a dávkování terapeutické užití MeSH
- diabetická noha * farmakoterapie metabolismus MeSH
- intravenózní podání MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikrocirkulace * účinky léků MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
Autologní buněčná terapie je už řadu let využívána u pacientů s chronickou končetinu ohrožující ischemií. Byly publikovány četné studie a metaanalýzy, které posuzovaly benefity terapie a představily i její nové možnosti. Kromě standardně využívaných zdrojů kmenových buněk (kostní dřeně a periferní krve) se otevírají nové možnosti využití jiných alternativ - různých typů tkání. Stále však přetrvává otázka porovnání účinků jednotlivých typů buněk a jejich aplikace. Velmi zajímavé jsou i možnosti kombinované terapie hyperbarickou oxygenoterapií společně s buněčnou terapií. Dle zkušenosti našeho pracoviště je autologní buněčná terapie efektivní metoda s nízkým počtem nežádoucích událostí.
Autologous cell therapy has been used in patients with chronic limb-threatening ischemia for many years. Numerous studies and meta-analyses assessed benefits of cell therapy and also presented its new possibilities. In addition to the standard sources of stem cells, like bone marrow and peripheral blood, new possibilities of using various types of tissues were considered. There is still question about a comparison of the effect among different types of cells and their administration. The possibility of combined therapy consisting of hyperbaric oxygen therapy and stem cell therapy is also an interesting approach. According to the experience from our centre, autologous cell therapy is an effective method with low rate of adverse events.
- MeSH
- amputace MeSH
- angioplastika metody MeSH
- autologní transplantace metody MeSH
- chronická kritická ischemie končetin diagnóza terapie MeSH
- diabetes mellitus 2. typu MeSH
- diabetická noha * diagnóza prevence a kontrola terapie MeSH
- hyperbarická oxygenace metody MeSH
- lidé MeSH
- transplantace kmenových buněk metody škodlivé účinky MeSH
- Check Tag
- lidé 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.
