Background Amputation-free survival (AFS) has been recommended as the gold standard for evaluating No-Option Critical Limb Ischemia (NO-CLI) therapy.Early-phase clinical trials suggest that autologous bone-marrow derived cells (BMCs) transplantation may have a positive effect on patients with NO-CLI,especially decreasing the incidence of amputation.However,the BMCs therapeutic efficacy remains controversial and whether BMCs therapy is suitable for all CLI patients is unclear.Methods We conducted a meta-analysis using data from randomized controlled trials (RCTs) by comparing autologous BMCs therapy with controls in patients with critical limb ischemia,and the primary endpoint is the incidence of amputation.Pubmed,EBSCO and the Cochrane Central Register of Controlled Trials (to approximately July 25,2012) were searched.Results Seven RCTs with 373 patients were enrolled in the meta-analysis.Because serious disease was the main reason leading to amputation in one trial,six studies with 333 patients were finally included in the meta-analysis.Pooling the data of the final six studies,we found that BMCs therapy significantly decreased the incidence of amputation in patients with CLI (odds ratio (OR),0.37; 95％ confidence interval (CI),0.22 to 0.62; P=0.0002),and the efficacy had not significantly declined within 6 months after BMCs were transplanted; OR,0.33; 95％ CI,0.16 to 0.70; P=0.004 within 6 months and OR,0.30; 95％ CI,0.11 to 0.79; P=0.01 within 3 months.The rate of AFS after BMCs therapy was significantly increased in patients with Rutherford class 5 CLI (OR 3.28; 95％ CI,1.12 to 9.65; P=0.03),while there was no significant improvement in patients with Rutherford class 4 (OR 0.35; 95％ CI,0.05 to 2.33; P=0.28) compared with controls.The BMCs therapy also improved ulcer healing (OR,5.83; 95％ CI,2.37 to 14.29; P=0.0001).Conclusions Our analysis suggests that autologous BMCs therapy has a beneficial effect in decreasing the incidence of amputation and the efficacy does not decrease significantly within 6 months after BMCs transplantation.Patients with Rutherford class 5 are suitable for BMCs therapy,while the efficiency in patients with Rutherford 4 needs further evaluation.
Last. Juraj Madaric(Cardiovascular Institute of the South)H-Index: 14
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Stem cell therapy has been proposed to be an alternative therapy in patients with critical limb ischemia (CLI), not eligible for endovascular or surgical revascularization. We compared the therapeutic effects of intramuscular (IM) and intra-arterial (IA) delivery of bone marrow cells (BMCs) and investigated the factors associated with therapeutic benefits. Forty-one patients (mean age, 66 ± 10 years; 35 males) with advanced CLI (Rutherford category, 5 and 6) not eligible for revascularization we...
Ixmyelocel-T is a patient-specific, expanded, multicellular therapy evaluated in patients with lower extremity critical limb ischemia (CLI) with no options for revascularization. This randomized, double-blind, placebo-controlled, phase 2 trial (RESTORE-CLI) compared the efficacy and safety of intramuscular injections of ixmyelocel-T with placebo. Patients received one-time injections over 20 locations in a single leg and were followed for 12 months. Safety assessments included occurrence of adve...
Objectives Despite advances in endovascular therapies, critical limb ischemia (CLI) continues to be associated with high morbidity and mortality. Patients without direct revascularization options have the worst outcomes. We sought to explore the feasibility of conducting a definitive trial of a bone marrow-derived cellular therapy for CLI in this "no option" population. Methods A pilot, multicenter, prospective, randomized, double-blind, placebo-controlled trial for "no option" CLI patients was ...
Last. Brian H. Annex(UVA: University of Virginia)H-Index: 62
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Objectives: The safety and efficacy of direct intramuscular injections of aldehyde dehydrogenase bright (ALDH br ) cells isolated from autologous bone marrow mononuclear cells (ABMMNCs) and ABMMNCs were studied in patients with critical limb ischemia (CLI) who were not eligible for percutaneous or surgical revascularization. Background: Many CLI patients are not candidates for current revascularization procedures, and amputation rates are high in these patients. Cell therapy may be a viable opti...
Objectives Cell therapy is a novel experimental treatment modality for patients with critical limb ischemia (CLI) of the lower extremities and no other established treatment options. This study was conducted to assess the safety and clinical efficacy of intramuscular injection of autologous tissue repair cells (TRCs). Methods A prospective, randomized double-blinded, placebo controlled, multicenter study (RESTORE-CLI) was conducted at 18 centers in the United States in patients with CLI and no o...
Last. Amit N. Patel(UofU: University of Utah)H-Index: 40
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Background Autologous bone marrow-derived stem cells have been ascribed an important therapeutic role in No-Option Critical limb Ischemia (NO-CLI). One primary endpoint for evaluating NO-CLI therapy is major amputation (AMP), which is usually combined with mortality for AMP-free survival (AFS). Only a trial which is double blinded can eliminate physician and patient bias as to the timing and reason for AMP. We examined factors influencing AMP in a prospective double-blinded pilot RCT (2:1 therap...
#1Debin Lu(Third Military Medical University)H-Index: 7
#2Bing Chen(Third Military Medical University)H-Index: 23
Last. Sihao Chen(Third Military Medical University)H-Index: 1
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Aims: To identify better cells for the treatment of diabetic critical limb ischemia (CLI) and foot ulcer in a pilot trial. Methods: Under ordinary treatment, thelimbs of 41type 2 diabetic patients with bilateralCLI and foot ulcer were injected intramuscularly with bone marrow mesenchymal stem cells (BMMSCs), bone marrow-derived mononuclear cells (BMMNCs), or normal saline (NS). Results: The ulcer healing rate of the BMMSC group was significantly higher than that of BMMNCs at 6 weeks after inject...
Background—Critical limb ischemia due to peripheral arterial occlusive disease is associated with a severely increased morbidity and mortality. There is no effective pharmacological therapy available. Injection of autologous bone marrow-derived mononuclear cells (BM-MNC) is a promising therapeutic option in patients with critical limb ischemia, but double-blind, randomized trials are lacking. Methods and Results—Forty patients with critical limb ischemia were included in a multicenter, phase II,...
Last. Angelo Avogaro(UNIPD: University of Padua)H-Index: 15
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Background: Peripheral arterial disease (PAD) is a common cause of disability and mortality. Up to one third of patients are not susceptible to traditional revascularization and may benefit from stem cell therapies. Objective: In this meta-analysis, we sought to determine whether autologous cell therapy is effective in the treatment of PAD. Methods: We searched the English literature in Medline, Excerpta Medica and the Cochrane database for trials of autologous cell therapy in patients with PAD ...
Fifty percent of diabetics (7% of general population) suffer from peripheral arterial occlusive disease, which may lead to amputation due to critical limb ischemia (CLI). The aim of our study was to prevent major limb amputation (MLA) in this group of patients using a local application of autologous bone marrow stem cells (ABMSC) concentrate. A total of 96 patients with CLI and foot ulcer (FU) were randomized into groups I and II. Patients in group I (n = 42, 36 males, 6 females, 66.2 ± 10.6 yea...
(1) Background: The treatment of peripheral arterial disease (PAD) is focused on improving perfusion and oxygenation in the affected limb. Standard revascularization methods include bypass surgery, endovascular interventional procedures, or hybrid revascularization. Cell-based therapy can be an alternative strategy for patients with no-option critical limb ischemia who are not eligible for endovascular or surgical procedures. (2) Aims: The aim of this narrative review was to provide an up-to-dat...
Last. Eugenio Baraldi(UNIPD: University of Padua)H-Index: 66
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The COVID-19 epidemic represents an unprecedented global health emergency, further aggravated by the lack of effective therapies. For this reason, several clinical trials are testing different off-label drugs, already approved for other pathologies. Mesenchymal stem/stromal cells (MSCs) have been tested during the last two decades for the treatment of various pathologic conditions, including acute and chronic lung diseases, both in animal models and in patients. In particular, promising results ...
BACKGROUND Cell therapy was proposed as a procedure of indirect revascularization for patients with critical ischaemia of lower extremities for whom endovascular and surgical revascularization is impossible. We present herein a review of the state of the art of studies in the field of cell therapy of this cohort of patients. BASIC PROVISIONS Cell therapy has proved safe, however, the results of studies of efficacy are relatively ambiguous and unconvincing. The number of patients in separately ta...
Last. Edouard Aboian(Palo Alto Medical Foundation)H-Index: 1
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Summary. Cell therapy is proposed for indirect revascularization for the patient’s incurable by endovascular or surgical revascularization. The therapy with stem cells (SCs) or progenitor cells is ...
BACKGROUND: Revascularisation is the gold standard therapy for patients with critical limb ischaemia (CLI). In over 30% of patients who are not suitable for or have failed previous revascularisation therapy (the 'no-option' CLI patients), limb amputation is eventually unavoidable. Preliminary studies have reported encouraging outcomes with autologous cell-based therapy for the treatment of CLI in these 'no-option' patients. However, studies comparing the angiogenic potency and clinical effects o...
OBJECTIVE: Treatment of wounds difficult to heal concerns 50% of the elderly population in Italy and is therefore an extreme relevance social burden. The present study shows how the treatment with autologous leuco-platelets reduces the healing time of wounds improving the functional recovery. PATIENTS AND METHODS: One hundred patients with ulcers of the legs were divided in two groups: 1) 50 patients treated with conventional therapies; 2) 50 patients treated with autologous leuco-platelet conce...
#1Shuang Bai Zhou(SJTU: Shanghai Jiao Tong University)H-Index: 1
#2Guo You Zhang(SJTU: Shanghai Jiao Tong University)H-Index: 1
Last. Qingfeng Li(SJTU: Shanghai Jiao Tong University)H-Index: 26
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Abstract Background Mechanical stretch, in term of skin expansion, can induce effective but limited in vivo skin regeneration for complex skin defect reconstruction. We propose a strategy to obtain regenerated skin by combining autologous stem cell transplantation with mechanical stretch. Methods This randomized, blinded placebo-controlled trial enrolled 38 adult patients undergoing skin expansion presenting with signs of exhausted regenerative capacity. Patients randomly received autologous bon...
Abstract Background aims Critical limb ischemia (CLI) is a major health problem worldwide, affecting approximately 500–1000 people per million per annum. Cell-based therapy has given new hope for the treatment of limb ischemia. This study assessed the safety and efficacy of cellular therapy CLI treatment. Methods We searched the PubMed, Embase and Cochrane databases through October 20, 2015, and selected the controlled trials with cell-based therapy for CLI treatment compared with cell-free trea...
Early-phase trials showed the feasibility and potential efficacy of cell therapy in patients with critical limb ischemia (CLI). For systematic review, randomized controlled trials (RCTs) of cell therapy versus no cell therapy in CLI were searched from PubMed and the Cochrane library databases. Outcome measures included major amputation, complete ulcer healing, ankle–brachial index (ABI), and all-cause mortality. Data were pooled using 16 RCTs, involving 774 patients. Compared with no cell therap...