Autologous cells derived from different sources and administered using different regimens for 'no-option' critical lower limb ischaemia patients.
Ontology highlight
ABSTRACT:
SUBMITTER: Abdul Wahid SF
PROVIDER: S-EPMC6513643 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BACKGROUND:Peripheral arterial disease is a major health problem, and in about 1% to 2% of patients the disease progresses to critical limb ischaemia (CLI). In a substantial number of patients with CLI, no effective treatment option other than amputation is available and around a quarter of these patients will require a major amputation during the following year. This is an update of the review first published in 2011. OBJECTIVES:To determine the effectiveness and safety of local intramuscular transplantation of autologous adult bone marrow mononuclear cells (BMMNCs) as a treatment for critical limb ischaemia (CLI). SEARCH METHODS:For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched February 2014) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 1). SELECTION CRITERIA:We included all randomised controlled trials of CLI in which participants were randomly allocated to intramuscular administration of autologous adult BMMNCs or control (either no intervention or conventional conservative therapy). We excluded studies on patients with intermittent claudication. DATA COLLECTION AND ANALYSIS:Two authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. Disagreements were resolved by consensus or by the third author. MAIN RESULTS:Only two small studies, with a combined total of 57 participants, met our inclusion criteria and were finally included. They were classified as having a moderate risk of bias with unclear issues regarding their methods, and according to the GRADE approach, the overall quality of the evidence would be considered as moderate. In one study the effects of intramuscular injections of BMMNCs in the ischaemic lower limbs of patients with CLI were compared with control (standard conservative treatment). No deaths were reported and no significant difference was observed between the two groups for either pain (P = 0.37) or the ankle brachial index (ABI) parameter. However, the treatment group showed a significantly smaller proportion of participants undergoing amputation compared with the control group (P = 0.026).In the other study, following subcutaneous injections of granulocyte colony-stimulating factor (G-CSF) for five days, peripheral blood derived mononuclear cells were collected and then transplanted by intramuscular injections into ischaemic lower limbs. The effects were compared with daily intravenous prostaglandin E1 injections (control group). No deaths were reported. Pain reduction was greater in the treatment group than in the control group (P < 0.001) as was increase in ABI (mean increase 0.13 versus 0.02, P < 0.01). The treatment group experienced a statistically significant increase in pain-free walking distance (PFWD) compared with the control group (mean increase 306.4 m versus 78.6 m, P = 0.007). A smaller proportion of participants underwent amputation in the treatment group compared with the control group (0% versus 36%, P = 0.007). AUTHORS' CONCLUSIONS:The data from the published trials suggest that there is insufficient evidence to support this treatment. These results were based on only two trials which had a very small number of participants. Therefore evidence from larger randomised controlled trials is needed in order to provide adequate statistical power to assess the role of intramuscular mononuclear cell implantation in patients with CLI.
| S-EPMC7175832 | biostudies-literature
Project description: Not available
| S-EPMC6491321 | biostudies-literature
Project description:Adipose-derived regenerative cell (ADRC) is a promising alternative source of autologous somatic stem cells for the repair of damaged tissue. This study aimed to assess the safety and feasibility of autologous ADRC implantation for therapeutic angiogenesis in patients with critical limb ischaemia (CLI). A clinical pilot study-Therapeutic Angiogenesis by Cell Transplantation using ADRCs (TACT-ADRC) study-was initiated in Japan. Adipose tissue was obtained by ordinary liposuction method. Isolated ADRCs were injected into the ischaemic limb. We performed TACT-ADRC procedure in five patients with CLI. At 6 months, no adverse events related to the TACT-ADRC were observed. No patients required major limb amputation, and ischaemic ulcers were partly or completely healed during the 6-month follow-up. In all cases, significant clinical improvements were seen in terms of rest pain and 6-min walking distance. Numbers of circulating CD34+ and CD133+ cells markers of progenitor cell persistently increased after ADRC implantation. The ratio of VEGF-A165b (an anti-angiogenic isoform of VEGF) to total VEGF-A in plasma significantly decreased after ADRC implantation. In vitro experiments, cultured with ADRC-conditioned media (CM) resulted in increased total VEGF-A and decreased VEGF-A165b in C2C12 cells, but not in macrophages. ADRC-CM also increased CD206+ cells expression and decreased TNF-α in macrophages. Autologous ADRC implantation was safe and effective in patients with CLI and could repair damaged tissue via its ability to promote angiogenesis and suppress tissue inflammation.
| S-EPMC7525513 | biostudies-literature
Project description:Patients with a decrease in limb perfusion with a potential threat to limb viability manifested by ischemic rest pain, ischemic ulcers, and/or gangrene are considered to have critical limb ischemia (CLI). Because of this generally poor outcome, there is a strong need for attempting any procedure to save the affected limb. The aim of this work is to evaluate the possibility to use stem cell therapy as a treatment option for patients with chronic critical lower limb ischemia with no distal run off. This study includes 20 patients with chronic critical lower limb ischemia with no distal run off who are unsuitable for vascular or endovascular option. These patients underwent stem cell therapy (SCT) by autologous transplantation of bone marrow derived mononuclear cells. 55 % of patients treated with SCT showed improvement of the rest pain after the first month, 60 % continued improvement of the rest pain after 6 months, 75 % after 1 year and 80 % after 2 years and continued without any deterioration till the third year. Limb salvage rate after STC was 80 % after the first year till the end of the second and third years. SCT can result in angiogenesis in patients with no-option CLI, providing a foundation for the application of this therapy to leg ischemia.
| S-EPMC4960127 | biostudies-other
Project description:BACKGROUND:Consensus is lacking regarding intervention for patients with acute lower limb ischaemia (ALI). The aim was to study amputation-free survival in patients treated for ALI by either primary open or endovascular revascularization. METHODS:The Swedish Vascular Registry (Swedvasc) was combined with the Population Registry and National Patient Registry to determine follow-up on mortality and amputation rates. Revascularization techniques were compared by propensity score matching 1?:?1. RESULTS:Of 9736 patients who underwent open surgery and 6493 who had endovascular treatment between 1994 and 2014, 3365 remained in each group after propensity score matching. Results are from the matched cohort only. Mean age of the patients was 74·7?years; 47·5 per cent were women and mean follow-up was 4·3?years. At 30-day follow-up, the endovascular group had better patency (83·0 versus 78·6 per cent; P <?0·001). Amputation rates were similar at 30?days (7·0 per cent in the endovascular group versus 8·2 per cent in the open group; P =?0·113) and at 1?year (13·8 versus 14·8 per cent; P =?0·320). The mortality rate was lower after endovascular treatment, at 30?days (6·7 versus 11·1 per cent; P <?0·001) and after 1?year (20·2 versus 28·6 per cent; P <?0·001). Accordingly, endovascular treatment had better amputation-free survival at 30?days (87·5 versus 82·1 per cent; P <?0·001) and 1?year (69·9 versus 61·1 per cent; P <?0·001). The number needed to treat to prevent one death within the first year was 12 with an endovascular compared with an open approach. Five years after surgery, endovascular treatment still had improved survival (HR 0·78, 99 per cent c.i. 0·70 to 0·86) but the difference between the treatment groups occurred mainly in the first year. CONCLUSION:Primary endovascular treatment for ALI appeared to reduce mortality compared with open surgery, without any difference in the risk of amputation.
| S-EPMC6221085 | biostudies-literature
Project description:The present study focuses on the application of a therapeutic strategy in patients with chronic severe lower limb ischaemia using a plasmid vector encoding the vascular endothelial growth factor (phVEGF(165)). It has been shown that VEGF promotes neo-vascularization and blood vessel network formation and thus might have the ability to improve blood-flow at the level of the affected limbs. However, little information is available regarding the necessary level of expression of VEGF and its possible related adverse effects. We have subcloned VEGF ( 165 )isoform into pCMV-Script expression vector (Stratagene) under the control of the CMV promoter. Three patients with chronic ischaemia of the lower limb, considered as not suitable for surgical re-vascularization, received intramuscular injection with 0.5 ml saline solution containing 10(11) copies of VEGF ( 165 ) plasmid. The clinical evolution has been monitored by angiography and estimated by walking time on the rolling carpet (Gardner protocol). Two months after therapy, all three patients showed complete relief of rest pain, improvement of ischaemic ulcer lesions and increased walking distance on the rolling carpet most probably due to appearance of newly formed collateral vessels.
| S-EPMC2276892 | biostudies-literature
Project description:Critical limb ischaemia (CLI) is the most advanced form of peripheral artery disease (PAD) and it is often associated with foot gangrene, which may lead to major amputation of lower limbs, and also with a higher risk of death due to fatal cardiovascular events. Matrix metalloproteinases (MMPs) seem to be involved in atherosclerosis, PAD and CLI. Aim of this study was to evaluate variations in MMP serum levels in patients affected by CLI, before and after lower limb surgical revascularisation through prosthetic or venous bypass. A total of 29 patients (7 females and 22 males, mean age 73·4 years, range 65-83 years) suffering from CLI and submitted to lower extremity bypass (LEB) in our Institution were recruited. Seven patients (group I) underwent LEB using synthetic polytetrafluoroethylene (PTFE) graft material and 22 patients (group II) underwent LEB using autogenous veins. Moreover, 30 healthy age-sex-matched subjects were also enrolled as controls (group III). We documented significantly higher serum MMPs levels (P < 0·01) in patients with CLI (groups I and II) with respect to control group (group III). Finally, five patients with CLI (17·2%) showed poor outcomes (major amputations or death), and enzyme-linked immunosorbent assay (ELISA) test showed very high levels of MMP-1 and MMP-8. MMP serum levels seem to be able to predict the clinical outcomes of patients with CLI.
| S-EPMC7949845 | biostudies-literature
Project description:Demonstrate the safety and effectiveness of highly purified CD133+ autologous stem cells in critical limb ischemia (CLI).Prospective single-center not randomized. Clinicaltrials.gov identifier: NCT01595776 METHODS: Eight patients with a history of stable CLI were enrolled in a period of 2 years. After bone marrow stimulation and single leukapheresis collection, CD133+ immunomagnetic cell selection was performed. CD133+ cells in buffer phosphate suspension was administered intramuscularly. Muscular and arterial contrast enhanced ultra sound (CEUS), lesion evolution and pain management were assessed preoperatively and 3, 6 and 12 months after the implant.No patient had early or late complications related to the procedure. Two patients (25 %) didn't get any relief from the treatment and underwent major amputation. Six patients (75 %) had a complete healing of the wounds, rest pain cessation and walking recovery. An increase in CEUS values was shown in all eight patients at 6 months and in the six clinical healed patients at 12 months and had statistical relevance.Highly purified autologous CD133+ cells can stimulate neo-angiogenesis, as based on clinical and CEUS data.
| S-EPMC4630831 | biostudies-literature
Project description:BackgroundInduction therapy followed by high-dose chemotherapy and autologous transplantation is the standard treatment for suitable patients with multiple myeloma.ObjectiveThe aim of this study was to assess whether induction therapy with thalidomidecontaining regimens was associated with improved results compared to vincristine, doxorubicin, and dexamethasone, and whether cyclophosphamide, thalidomide, and dexamethasone were associated with better results than thalidomide and dexamethasone.MethodsThe records of 152 patients who underwent autologous transplantation at this institution from August of 2004 to January of 2012 were reviewed, selecting those with at least partial response to a maximum of eight cycles of induction therapy and sufficient follow-up information for analysis.ResultsThis study included 89 patients; 44 were female, with a mean age of 55 years (there was a significant trend for increasing age over the years of the study).The median number of induction therapy cycles was four, again with a trend of increase over the years.At least a very good partial response to induction therapy was achieved more often in the cyclophosphamide, thalidomide, and dexamethasone group (61.1%) and in the thalidomide and dexamethasone group (59.2%) than in the vincristine, doxorubicin, and dexamethasone group (16.2%). The overall median progression-free survival was 34 months, with no statistically significant difference between the three groups. The overall median survival was not reached, and there was no significant difference between the three groups; the estimated five-year overall survival was 55%.ConclusionAlthough the quality of responses appeared to be better with thalidomidecontaining regimens, these improvements did not translate into improved long-term outcomes. Given its track record, cyclophosphamide, thalidomide, and dexamethasone is currently considered the preferred regimen for first-line induction therapy in the Brazilian public health system.
| S-EPMC3948661 | biostudies-literature
Project description:The evidence for lower limb flap (LLF) training regimens is equivocal. The commonest cause of LLF failure is venous congestion. The aim of this study was to investigate whether venous congestion could be reduced by patient-led isometric calf contractions during flap training. A prospective clinical study was conducted using photospectroscopy and laser Doppler (Oxygen to See) to assess healthy limbs and LLF characteristics during flap training and isometric calf contractions. Tissue oxygen saturation, venous congestion, and blood flow were measured at rest, as well as during and after limb dangling and calf contraction exercises. In the acute postoperative period following LLF surgery, dependency markedly reduced superficial flow (-55.20% ± 19.17%), with a concurrent increase in venous congestion (33.80% ± 28.80%); supine isometric contractions improved superficial flow and reduced venous congestion from postoperative day 5. Contractions cause a significant increase in blood flow in the outpatient cohort (+84.40% ± 7.86%, P = 0.009), with a mean time since discharge of 14 weeks. Our data suggest patient-led isometric calf exercises are well tolerated and may reduce venous congestion in the acute phase. Progressive changes toward normal physiological function were demonstrated in the outpatient rehabilitation period. Incorporating calf exercises into LLF rehabilitation may allow longer periods of leg dependency, quicker recovery from surgery, and ultimately improve outcomes.
| S-EPMC7253290 | biostudies-literature