SS19 Intramuscular Injection of Autologous Bone Marrow Cells to Prevent Amputation in Critical Limb Ischemia: The Results of the Phase III MOBILE Trial

Murphy, Michael P.; Ross, Charles B.; Kibbe, Melina R.; Kelso, Rebecca; Sharafuddin, Mel J.; Tzeng, Edith; Wang, Keisin; Wilson, Michael G.

doi:10.1016/j.jvs.2017.03.247

Cited by 5 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Subgroup analyses of double-blind multicenter RCT, MOBILE, demonstrate that an intramuscular injection of BM-MNCs can prevent major amputations (secondary endpoint) in Rutherford 4 and 5 non-diabetics (amputation: 16% of stem cell group versus 22% of placebo group; p = 0.39) [21]. Similar results were obtained in another multicenter placebo-controlled RCT, BALI, which involved 38 patients [22].…”

Section: Cells Derived From the Human Bone Marrowsupporting

confidence: 60%

Cell therapy of critical limb ischemia-problems and prospects

Osipova

Saaya

Карпенко

et al. 2019

Vasa

View full text Add to dashboard Cite

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 assumed to be more efficient as compared with protein or gene therapy not only because of their direct vasculogenic properties, but also thanks to their paracrine effect via secretion of manifold biologically active substances. This review gives an overview of the potential of SC-based therapy for critical limb ischemia (CLI), putative mechanism underlying cell therapy, and comparison of cell therapy to angiogenesis gene therapy in CLI treatment. Human trial data and meta-analysis, as well as some problems of clinical trials and considerations for future SC-based therapy in CLI are also discussed.

show abstract

Section: Cells Derived From the Human Bone Marrowsupporting

confidence: 60%

Cell therapy of critical limb ischemia-problems and prospects

Osipova

Saaya

Карпенко

et al. 2019

Vasa

View full text Add to dashboard Cite

show abstract

“…528,530 Another trial of 152 patients found little difference in AFS between the treatment group and control group at 6 months (80% vs 69%; P ¼ .224). 529,531 Both of these phase 3 trials are being conducted through investigator device exemptions from the Center for Devices and Radiological Health of the FDA.…”

Section: Trials Of Gene and Stem Cell Therapy In Cltimentioning

confidence: 99%

Global vascular guidelines on the management of chronic limb-threatening ischemia

Conte

Bradbury

Kolh³

et al. 2019

Journal of Vascular Surgery

1,189

865

View full text Add to dashboard Cite

Chronic limb-threatening ischemia (CLTI) is associated with mortality, amputation, and impaired quality of life. These Global Vascular Guidelines (GVG) are focused on definition, evaluation, and management of CLTI with the goals of improving evidence-based care and highlighting critical research needs. The term CLTI is preferred over critical limb ischemia, as the latter implies threshold values of impaired perfusion rather than a continuum. CLTI is a clinical syndrome defined by the presence of peripheral artery disease (PAD) in combination with rest pain, gangrene, or a lower limb ulceration >2 weeks duration. Venous, traumatic, embolic, and nonatherosclerotic etiologies are excluded. All patients with suspected CLTI should be referred urgently to a vascular specialist. Accurately staging the severity of limb threat is fundamental, and the Society for Vascular Surgery Threatened Limb Classification system, based on grading of Wounds, Ischemia, and foot Infection (WIfI) is endorsed. Objective hemodynamic testing, including toe pressures as the preferred measure, is required to assess CLTI. Evidence-based revascularization (EBR) hinges on three independent axes: Patient risk, Limb severity, and ANatomic complexity (PLAN). Average-risk and high-risk patients are defined by estimated procedural and 2-year all-cause mortality. The GVG proposes a new Global Anatomic Staging System (GLASS), which involves defining a preferred target artery path (TAP) and then estimating limb-based patency (LBP), resulting in three stages of complexity for intervention. The optimal revascularization strategy is also influenced by the availability of autogenous vein for open bypass surgery. Recommendations for EBR are based on best available data, pending level 1 evidence from ongoing trials. Vein bypass may be preferred for average-risk patients with advanced limb threat and high complexity disease, while those with less complex anatomy, intermediate severity limb threat, or high patient risk may be favored for endovascular intervention. All patients with CLTI should be afforded best medical therapy including the use of antithrombotic, lipid-lowering, antihypertensive, and glycemic control agents, as well as counseling on smoking cessation, diet, exercise, and preventive foot care. Following EBR, long-term limb surveillance is advised. The effectiveness of nonrevascularization therapies (eg, spinal stimulation, pneumatic compression, prostanoids, and hyperbaric oxygen) has not been established. Regenerative medicine approaches (eg, cell, gene therapies) for CLTI should be restricted to rigorously conducted randomizsed clinical trials. The GVG promotes standardization of study designs and end points for clinical trials in CLTI. The importance of multidisciplinary teams and centers of excellence for amputation prevention is stressed as a key health system initiative.

show abstract

“…Tissue ischemia is prevalent in diabetes and patients could benefit from an autologous cell therapy that promotes vascular repair. Unfortunately, a recent report on the MOBILE trial suggested the effectiveness of an autologous cell therapy for critical limb ischemia is limited to nondiabetic patients . In addition, there is accumulating evidence to suggest that MACs are dysfunctional in diabetes.…”

Section: Introductionmentioning

confidence: 99%

The Vasoreparative Function of Myeloid Angiogenic Cells Is Impaired in Diabetes Through the Induction of IL1β

et al. 2018

View full text Add to dashboard Cite

Myeloid angiogenic cells (MACs) promote revascularization through the paracrine release of angiogenic factors and have been harnessed as therapeutic cells for many ischemic diseases. However, their proangiogenic properties have been suggested to be diminished in diabetes. This study investigates how the diabetic milieu affects the immunophenotype and function of MACs. Both MACs isolated from diabetic conditions and healthy cells exposed to a diabetic environment were used to determine the potential of MACs as a cell therapy for diabetic‐related ischemia. MACs were isolated from human peripheral blood and characterized alongside proinflammatory macrophages M (LPS + IFNγ) and proangiogenic macrophages M (IL4). Functional changes in MACs in response to high‐d‐glucose were assessed using an in vitro 3D‐tubulogenesis assay. Phenotypic changes were determined by gene and protein expression analysis. Additionally, MACs from type 1 diabetic (T1D) patients and corresponding controls were isolated and characterized. Our evidence demonstrates MACs identity as a distinct macrophage subtype that shares M2 proangiogenic characteristics, but can be distinguished by CD163hi expression. High‐d‐glucose treatment significantly reduced MACs proangiogenic capacity, which was associated with a significant increase in IL1β mRNA and protein expression. Inhibition of IL1β abrogated the antiangiogenic effect induced by high‐d‐glucose. IL1β was also significantly upregulated in MACs isolated from T1D patients with microvascular complications compared to T1D patients without microvascular complications or nondiabetic volunteers. This study demonstrates that Type 1 diabetes and diabetic‐like conditions impair the proangiogenic and regenerative capacity of MACs, and this response is mediated by IL‐1β. Stem Cells 2018;36:834–843

show abstract

SS19 Intramuscular Injection of Autologous Bone Marrow Cells to Prevent Amputation in Critical Limb Ischemia: The Results of the Phase III MOBILE Trial

Cited by 5 publications

References 0 publications

Cell therapy of critical limb ischemia-problems and prospects

Cell therapy of critical limb ischemia-problems and prospects

Global vascular guidelines on the management of chronic limb-threatening ischemia

The Vasoreparative Function of Myeloid Angiogenic Cells Is Impaired in Diabetes Through the Induction of IL1β

Contact Info

Product

Resources

About