Local intramuscular transplantation of autologous bone marrow mononuclear cells for critical lower limb ischaemia.
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ABSTRACT:
SUBMITTER: Moazzami B
PROVIDER: S-EPMC9266992 | biostudies-literature | 2022 Jul
REPOSITORIES: biostudies-literature
Publications
Local intramuscular transplantation of autologous bone marrow mononuclear cells for critical lower limb ischaemia.
Moazzami Bobak B Mohammadpour Zinat Z Zabala Zohyra E ZE Farokhi Ermia E Roohi Aria A Dolmatova Elena E Moazzami Kasra K
The Cochrane database of systematic reviews 20220708
<h4>Background</h4>Peripheral arterial disease is a major health problem, and in about 1% to 2% of patients, the disease progresses to critical limb ischaemia (CLI), also known as critical limb-threatening ischaemia. In a substantial number of individuals with CLI, no effective treatment options other than amputation are available, with around a quarter of these patients requiring a major amputation during the following year. This is the second update of a review first published in 2011.<h4>Obje ...[more]
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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: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 & objectivesPlatelet concentrate contains a rich cocktail of growth factors that support growth and proliferation of cells. The primary goal of this study was to investigate the safety of platelet lysate (PL) in patients with critical limb ischaemia (CLI) not suitable for standard revascularization. Data on the preliminary efficacy are also presented.MethodsSeven patients (18-70 yr) with CLI classified in the Rutherford grades 3-5, with history of intermittent claudication for more than eight weeks and were not suitable for standard revascularization, underwent autologous intramuscular injections of PL. These patients were examined physically alongside other parameters such as TcPO2, toe pressure, and ankle brachial index, at baseline and were followed up for 12 months.ResultsThe procedure was well tolerated with no serious adverse or any adverse events reported during follow up. Although not the primary aim of this report, preliminary data showed significant clinical improvement in Rutherford stage, ankle-brachial index and toe pressure which persisted for a year.Interpretation & conclusionsIntramuscular injection of PL was well tolerated with no major adverse events reported in our study participants. With the observed satisfactory safety data, preliminary efficacy data of PL should be further validated.
| S-EPMC9629534 | biostudies-literature
Project description: Not available
| S-EPMC6513643 | biostudies-literature
Project description:Cell therapy is being widely explored in the management of stroke and has demonstrated great potential. It has been shown to assist in the remodeling of the central nervous system by inducing neurorestorative effect through the process of angiogenesis, neurogenesis, and reduction of glial scar formation. In this study, the effect of intrathecal administration of autologous bone marrow mononuclear cells (BMMNCs) is analyzed on the recovery process of patients with chronic stroke. 24 patients diagnosed with chronic stroke were administered cell therapy, followed by multidisciplinary neurorehabilitation. They were assessed on functional independence measure (FIM) objectively, along with assessment of standing and walking balance, ambulation, and hand functions. Out of 24 patients, 12 improved in ambulation, 10 in hand functions, 6 in standing balance, and 9 in walking balance. Further factor analysis was done. Patients of the younger groups showed higher percentage of improvement in all the areas. Patients who underwent cell therapy within 2 years after the stroke showed better changes. Ischemic type of stroke had better recovery than the hemorrhagic stroke. This study demonstrates the potential of autologous BMMNCs intrathecal transplantation in improving the prognosis of functional recovery in chronic stage of stroke. Further clinical trials are recommended. This trial is registered with NCT02065778.
| S-EPMC4121152 | biostudies-literature
Project description:The purpose of this Phase I open label nonrandomized trial was to assess the safety and efficacy of autologous bone marrow mononuclear cell (ABMNC) therapy in promoting amputation-free survival (AFS) in patients with critical limb ischemia (CLI).Between September 2005 and March 2009, 29 patients (30 limbs), with a median age of 66 years (range, 23-84 years; 14 male, 15 female) with CLI were enrolled. Twenty-one limbs presented with rest pain (RP), six with RP and ulceration, and three with ulcer only. All patients were not candidates for surgical bypass due to absence of a patent artery below the knee and/or endovascular approaches to improving perfusion was not possible as determined by an independent vascular surgeon. Patients were treated with an average dose of 1.7 ± 0.7 × 10(9) ABMNC injected intramuscularly in the index limb distal to the anterior tibial tuberosity. The primary safety end point was accumulation of serious adverse events, and the primary efficacy end point was AFS at 1 year. Secondary end points at 12 weeks posttreatment were changes in first toe pressure (FTP), toe-brachial index (TBI), ankle-brachial index (ABI), and transcutaneous oxygen measurements (TcPO(2)). Perfusion of the index limb was measured with positron emission tomography-computed tomography (PET-CT) with intra-arterial infusion of H(2)O(15). RP, using a 10-cm visual analogue scale, quality of life using the VascuQuol questionnaire, and ulcer healing were assessed at each follow-up interval. Subpopulations of endothelial progenitor cells were quantified prior to ABMNC administration using immunocytochemistry and fluorescent-activated cell sorting.There were two serious adverse events; however, there were no procedure-related deaths. Amputation-free survival at 1 year was 86.3%. There was a significant increase in FTP (10.2 ± 6.2 mm Hg; P = .02) and TBI (0.10 ± 0.05;P = .02) and a trend in improvement in ABI (0.08 ± 0.04; P = .73). Perfusion index by PET-CT H(2)O(15) increased by 19.3 ± 3.1, and RP decreased significantly by 2.2 ± 0.6 cm (P = .02). The VascuQol questionnaire demonstrated significant improvement in quality of life, and three of nine ulcers (33%) healed completely. KDR(+) but not CD34(+) or CD133(+) subpopulations of ABMNC were associated with improvement in limb perfusion.This Phase I study has demonstrated safety, and the AFS rates suggest efficacy of ABMNC in promoting limb salvage in "no option" CLI. Based on these results, we plan to test the concept that ABMNCs improve AFS at 1 year in a Phase III randomized, double-blinded, multicenter trial.
| S-EPMC3102148 | biostudies-literature
Project description:IntroductionOur study was designed to investigate the safety and efficacy of combined autologous bone marrow mononuclear cell (MNC) and gene therapy in comparison to conventional drug therapy in patients with critical limb ischemia (CLI).Material and methodsThirty-two patients with CLI persisting for 12-48 months (average time 27.5 months) were randomized into 2 groups, each group consisting of 16 patients. In the first group, administration of autologous bone marrow MNC and vascular endothelial growth factor (VEGF) plasmid was performed. The patients from the second group were treated pharmacologically with pentoxifylline. Ankle-brachial index (ABI) was measured and angiography was performed before and finally 3 months after treatment. The pain was evaluated using the Visual Analog Scale (VAS) before and after 3 months.ResultsAnkle-brachial index improved significantly from 0.29 ±0.21 to 0.52 ±0.23 (p < 0.001) in 12 patients (75.0%) 3 months after the experimental therapy in group 1. In this group angiography showed the development of collateral vessels. Ischemic ulcers healed completely in 11 patients (68.75%). In group 2 the ABI did not improve in any patient; moreover the complete healing of skin ulcers was not found in any of the patients of this group. Amputation was performed in 4 (25.0%) patients in group 1, and in 8 patients (50%) from group 2.ConclusionsThese data after 3-month follow-up indicate that intramuscular injection of MNC combined with gene therapy in patients with chronic CLI is safe, and a more feasible and effective method of treatment than the conventional therapy. However, both therapies are limited by the degree of microcirculation damage.
| S-EPMC4424239 | biostudies-literature
Project description: Not available
| S-EPMC6491321 | biostudies-literature
Project description:Our goal was to evaluate early results of the clinical application of autologous whole bone marrow stem cell transplantation (AWBMSCT) for critical limb ischemia (CLI) in patients with Buerger's disease. We retrospectively analyzed the data of 58 limbs of 37 patients (mean age, 43.0 years; range, 28-63 years; male, 91.9%) with Buerger's disease with CLI who were treated with AWBMSCT from March 2013 to December 2014. We analyzed Rutherford category, pain score, pain-free walking time (PFWT), total walking time (TWT), ankle brachial pressure index (ABPI), and toe brachial pressure index (TBPI), and investigated wound healing and occurrence of unplanned amputations. The mean follow-up duration was 11.9 ± 7.2 months (range, 0.9-23.9 months) and 100%, 72.4%, and 74.1% of patients were available to follow-up 1, 3 and 6 months after AWBMST, respectively. At 6 months, patients demonstrated significant improvements in Rutherford category (P < 0.0001), pain score (P < 0.0001), PFWT (P < 0.0001) and TBPI (P < 0.0001). ABPI was increased compared to baseline, but the difference was not significant. A total of 76.5% ischemic wounds achieved complete or improved healing. AWBMSCT is a safe and effective alternative or adjunctive treatment modality to achieve clinical improvement in patients with CLI.
| S-EPMC4726399 | biostudies-other
Project description: Not available
| S-EPMC6478298 | biostudies-literature