Cell therapy of critical limb ischemia in diabetic patients – State of art

2017 ◽  
Vol 126 ◽  
pp. 263-271 ◽  
Author(s):  
Michal Dubský ◽  
Alexandra Jirkovská ◽  
Robert Bem ◽  
Andrea Nemcová ◽  
Vladimira Fejfarová ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Critical Limb Ischemia ◽  
Limb Ischemia ◽  
Diabetic Patients ◽  
State Of Art

scholarly journals Clinical and (31)P magnetic resonance spectroscopy characterization of patients with critical limb ischemia before and after autologous cell therapy

2019 ◽  
pp. 559-566
Author(s):  
M. Dubský ◽  
P. Šedivý ◽  
A. Němcová ◽  
M. Drobný ◽  
J. Hazdrová ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Cell Therapy ◽  
Critical Limb Ischemia ◽  
Limb Ischemia ◽  
Resonance Spectroscopy ◽  
Diabetic Patients ◽  
Transcutaneous Oxygen ◽  
Autologous Cell ◽  
Autologous Cell Therapy

Autologous cell therapy (ACT) is a new treatment method for diabetic patients with critical limb ischemia (CLI) not eligible for standard revascularization. After intramuscular injection of bone marrow-derived mononuclear cells local arteriogenesis in the ischemic tissue occurs. Studies assessing visualization of this therapeutic vasculogenesis after ACT by novel imaging techniques are lacking. The aim of our study was to assess the effect of ACT on possible metabolic changes and perfusion of critically ischemic limbs using (31)P magnetic resonance spectroscopy ((31)P MRS) and its possible correlation with changes of transcutaneous oxygen pressure (TcPO2). Twenty-one patients with diabetes and no-option CLI treated by ACT in our foot clinic over 8 years were included in the study. TcPO2 as well as rest (phosphocreatine, adenosine triphosphate and inorganic phosphate) and dynamic (mitochondrial capacity and phosphocreatine recovery time) (31)P-MRS parameters were evaluated at baseline and 3 months after cell treatment. TcPO2 increased significantly after 3 months compared with baseline (from 22.4±8.2 to 37.6±13.3 mm Hg, p=0.0002). Rest and dynamic (31)P MRS parameters were not significantly different after ACT in comparison with baseline values. Our study showed a significant increase of TcPO2 on the dorsum of the foot after ACT. We did not observe any changes of rest or dynamic (31)P MRS parameters in the area of the proximal calf where the cell suspension has been injected into.

scholarly journals Perfusion Scintigraphy in the Assessment of Autologous Cell Therapy in Diabetic Patients With Critical Limb Ischemia

2018 ◽  
pp. 583-589 ◽  
Author(s):  
A. NEMCOVA ◽  
A. JIRKOVSKA ◽  
M. DUBSKY ◽  
R. BEM ◽  
V. FEJFAROVA ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Critical Limb Ischemia ◽  
Limb Ischemia ◽  
Diabetic Patients ◽  
Perfusion Scintigraphy ◽  
Transcutaneous Oxygen ◽  
Autologous Cell ◽  
Autologous Cell Therapy ◽  
99Mtc Mibi ◽  
Calf Muscles

Perfusion scintigraphy with technetium-99-methoxy-isobutyl-isonitrile (99mTc-MIBI) is often used for assessing myocardial function but the number of studies concerning lower limb perfusion is limited. The aim of our study was to assess whether 99mTc-MIBI was an eligible method for evaluation of the effect of cell therapy on critical limb ischemia (CLI) in diabetic patients. 99mTc-MIBI of calf muscles was performed before and 3 months after autologous cell therapy (ACT) in 24 diabetic patients with CLI. Scintigraphic parameters such as rest count and exercising count after a stress test were defined. These parameters and their ratios were compared between treated and untreated (control) limbs and with changes in transcutaneous oxygen pressure (TcPO2) that served as a reference method. The effect of ACT was confirmed by a significant increase in TcPO2 values (p˂0.001) at 3 months after ACT. We did not observe any significant changes of scintigraphic parameters both at rest and after stress 3 months after ACT, there were no differences between treated and control limbs and no association with TcPO2 changes. Results of our study showed no significant contribution of 99mTc-MIBI of calf muscles to the assessment of ACT in diabetic patients with CLI over a 3-month follow-up period.

Role of Serum Levels of Angiogenic Cytokines in Assessment of Angiogenesis after Stem Cell Therapy of Diabetic Patients with Critical Limb Ischemia

2014 ◽  
Vol 23 (12) ◽  
pp. 1517-1523 ◽  
Author(s):  
Michal Dubsky ◽  
Alexandra Jirkovska ◽  
Robert Bem ◽  
Vladimira Fejfarova ◽  
Martin Varga ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Critical Limb Ischemia ◽  
Limb Ischemia ◽  
Serum Levels ◽  
Diabetic Patients ◽  
Angiogenic Cytokines

Main Factors Predicting Nonresponders to Autologous Cell Therapy for Critical Limb Ischemia in Patients With Diabetic Foot

Angiology ◽  
2021 ◽  
pp. 000331972110056
Author(s):  
Michal Dubský ◽  
Vladimíra Fejfarová ◽  
Robert Bem ◽  
Alexandra Jirkovská ◽  
Andrea Nemcová ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Critical Limb Ischemia ◽  
Diabetic Foot ◽  
Univariate Analysis ◽  
Limb Ischemia ◽  
Stepwise Logistic Regression ◽  
Diabetic Patients ◽  
Transcutaneous Oxygen ◽  
Autologous Cell ◽  
Autologous Cell Therapy

Autologous cell therapy (ACT) is a new treatment for patients with no-option critical limb ischemia (NO-CLI). We evaluated the factors involved in the nonresponse to ACT in patients with CLI and diabetic foot. Diabetic patients (n = 72) with NO-CLI treated using ACT in our foot clinic over a period of 8 years were divided into responders (n = 57) and nonresponders (n = 15). Nonresponder was defined as an insufficient increase in transcutaneous oxygen pressure by <5 mm Hg, 3 months after ACT. Patient demographics, diabetes duration and treatment, and comorbidities as well as a cellular response to ACT, limb-related factors, and the presence of inherited thrombotic disorders were compared between the 2 groups. The main independent predictors for an impaired response to ACT were heterozygote Leiden mutation (OR 10.5; 95% CI, 1.72-4) and homozygote methylenetetrahydrofolate reductase (MTHFR 677) mutation (OR 3.36; 95% CI, 1.0-14.3) in stepwise logistic regression. Univariate analysis showed that lower mean protein C levels ( P = .041) were present in nonresponders compared with responders. In conclusion, the significant predictors of an impaired response to ACT in diabetic patients with NO-CLI were inherited thrombotic disorders.

scholarly journals Comparative analysis of mouse bone marrow and adipose tissue mesenchymal stem cells for critical limb ischemia cell therapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pegah Nammian ◽  
Seyedeh-Leili Asadi-Yousefabad ◽  
Sajad Daneshi ◽  
Mohammad Hasan Sheikhha ◽  
Seyed Mohammad Bagher Tabei ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Cell Therapy ◽  
Femoral Artery ◽  
Critical Limb Ischemia ◽  
Limb Ischemia

Abstract Introduction Critical limb ischemia (CLI) is the most advanced form of peripheral arterial disease (PAD) characterized by ischemic rest pain and non-healing ulcers. Currently, the standard therapy for CLI is the surgical reconstruction and endovascular therapy or limb amputation for patients with no treatment options. Neovasculogenesis induced by mesenchymal stem cells (MSCs) therapy is a promising approach to improve CLI. Owing to their angiogenic and immunomodulatory potential, MSCs are perfect candidates for the treatment of CLI. The purpose of this study was to determine and compare the in vitro and in vivo effects of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue mesenchymal stem cells (AT-MSCs) on CLI treatment. Methods For the first step, BM-MSCs and AT-MSCs were isolated and characterized for the characteristic MSC phenotypes. Then, femoral artery ligation and total excision of the femoral artery were performed on C57BL/6 mice to create a CLI model. The cells were evaluated for their in vitro and in vivo biological characteristics for CLI cell therapy. In order to determine these characteristics, the following tests were performed: morphology, flow cytometry, differentiation to osteocyte and adipocyte, wound healing assay, and behavioral tests including Tarlov, Ischemia, Modified ischemia, Function and the grade of limb necrosis scores, donor cell survival assay, and histological analysis. Results Our cellular and functional tests indicated that during 28 days after cell transplantation, BM-MSCs had a great effect on endothelial cell migration, muscle restructure, functional improvements, and neovascularization in ischemic tissues compared with AT-MSCs and control groups. Conclusions Allogeneic BM-MSC transplantation resulted in a more effective recovery from critical limb ischemia compared to AT-MSCs transplantation. In fact, BM-MSC transplantation could be considered as a promising therapy for diseases with insufficient angiogenesis including hindlimb ischemia.

Long-Term Clinical Outcomes of Infrapopliteal Drug-Eluting Stent Placement for Critical Limb Ischemia in Diabetic Patients

2015 ◽  
Vol 26 (10) ◽  
pp. 1423-1430 ◽  
Author(s):  
Stavros Spiliopoulos ◽  
Vasiliki Theodosiadou ◽  
Konstantinos Katsanos ◽  
Panagiotis Kitrou ◽  
George C. Kagadis ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Critical Limb Ischemia ◽  
Stent Placement ◽  
Limb Ischemia ◽  
Drug Eluting Stent ◽  
Diabetic Patients ◽  
Drug Eluting

Use of Tapered Balloons to Recanalize Occluded Below-the-Knee Arteries in Diabetic Patients with Critical Limb Ischemia

2016 ◽  
Vol 31 ◽  
pp. 105-110
Author(s):  
Nicola Troisi ◽  
Leonardo Ercolini ◽  
Emiliano Chisci ◽  
Piefrancesco Frosini ◽  
Clara Pigozzi ◽  
...  
Keyword(s):  
Critical Limb Ischemia ◽  
Limb Ischemia ◽  
Diabetic Patients ◽  
Below The Knee

scholarly journals Cell Therapy in Patients with Critical Limb Ischemia

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Rita Compagna ◽  
Bruno Amato ◽  
Salvatore Massa ◽  
Maurizio Amato ◽  
Raffaele Grande ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Critical Limb Ischemia ◽  
Limb Ischemia ◽  
Tissue Loss ◽  
Systematic Analysis ◽  
Peripheral Arterial Obstructive Disease ◽  
Peripheral Arterial ◽  
Cellular Components

Critical limb ischemia (CLI) represents the most advanced stage of peripheral arterial obstructive disease (PAOD) with a severe obstruction of the arteries which markedly reduces blood flow to the extremities and has progressed to the point of severe rest pain and/or even tissue loss. Recent therapeutic strategies have focused on restoring this balance in favor of tissue survival using exogenous molecular and cellular agents to promote regeneration of the vasculature. These are based on stimulation of angiogenesis by extracellular and cellular components. This review article carries out a systematic analysis of the most recent scientific literature on the application of stem cells in patients with CLI. The results obtained from the detailed analysis of the recent literature data have confirmed the beneficial role of cell therapy in reducing the rate of major amputations in patients with CLI and improving their quality of life.

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