Cellular Therapy With Ixmyelocel-T to Treat Critical Limb Ischemia: The Randomized, Double-blind, Placebo-controlled RESTORE-CLI Trial

Powell, Richard J.; Marston, William A.; Berceli, Scott A.; Guzman, Raul J.; Henry, Timothy D.; Longcore, Amy; Stern, Theresa; Watling, Sharon M.; Bartel, Ronnda L.

doi:10.1038/mt.2012.52

Cited by 136 publications

(110 citation statements)

References 16 publications

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“…7,21,22 To allow comparisons with recently published clinical trials, we included previously published composite outcomes for success and failure of cell-based therapy. 23,24 Clinical evaluation by the same investigator, treadmill exercise testing, and tco 2 measurement were performed at baseline and at 2 and 6 months follow-up.…”

Section: Surveillance Protocol and Outcome Assessmentmentioning

confidence: 99%

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Effect of Repetitive Intra-Arterial Infusion of Bone Marrow Mononuclear Cells in Patients With No-Option Limb Ischemia

Teraa¹,

Sprengers²,

Schutgens³

et al. 2015

Circulation

160

103

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Background— Patients with severe limb ischemia may not be eligible for conventional therapeutic interventions. Pioneering clinical trials suggest that bone marrow–derived cell therapy enhances neovascularization, improves tissue perfusion, and prevents amputation. The objective of this trial was to determine whether repetitive intra-arterial infusion of bone marrow mononuclear cells (BMMNCs) in patients with severe, nonrevascularizable limb ischemia can prevent major amputation. Methods and Results— The Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra-arterial Supplementation (JUVENTAS) trial is a randomized, double-blind, placebo-controlled clinical trial in 160 patients with severe, nonrevascularizable limb ischemia. Patients were randomly assigned to repetitive (3 times; 3-week interval) intra-arterial infusion of BMMNC or placebo. No significant differences were observed for the primary outcome, ie, major amputation at 6 months, with major amputation rates of 19% in the BMMNC versus 13% in the placebo group (relative risk, 1.46; 95% confidence interval, 0.62–3.42). The safety outcome (all-cause mortality, occurrence of malignancy, or hospitalization due to infection) was not significantly different between the groups (relative risk, 1.46; 95% confidence interval, 0.63–3.38), neither was all-cause mortality at 6 months with 5% versus 6% (relative risk, 0.78; 95% confidence interval, 0.22–2.80). Secondary outcomes quality of life, rest pain, ankle-brachial index, and transcutaneous oxygen pressure improved during follow-up, but there were no significant differences between the groups. Conclusions— Repetitive intra-arterial infusion of autologous BMMNCs into the common femoral artery did not reduce major amputation rates in patients with severe, nonrevascularizable limb ischemia in comparison with placebo. The general improvement in secondary outcomes during follow-up in both the BMMNC and the placebo group, as well, underlines the essential role for placebo-controlled design of future trials. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00371371.

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Section: Surveillance Protocol and Outcome Assessmentmentioning

confidence: 99%

“…‡Composite end point as defined by Powell et al 23 Success is defined as being alive, without major amputation of the index leg, and no doubling in wound size or de novo gangrene.…”

Section: Hemodynamic Measurements and Ulcer Healingmentioning

confidence: 99%

Effect of Repetitive Intra-Arterial Infusion of Bone Marrow Mononuclear Cells in Patients With No-Option Limb Ischemia

Teraa¹,

Sprengers²,

Schutgens³

et al. 2015

Circulation

160

103

View full text Add to dashboard Cite

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“…since that time, numerous other studies have examined the efficacy and safety of cell therapy for Pad, with varying results (tables 1 and 2). [22][23][24][25][26][27][28][29][30][31][32][33] Most clinical trials of cell therapy for Pad have consisted of uncontrolled patient series, with few randomized, properly controlled studies. sample sizes have been relatively small, with most studies enrolling fewer than 50 patients.…”

Section: Vascular Regeneration In Padmentioning

confidence: 99%

“…[22][23][24][25][26][27][28][29][30][31][32][33] Procedures associated with cell therapy, such as bone marrow aspiration and injection, were generally well-tolerated by the patients, with few adverse events reported. hence, current data is promising, and safety concerns do not outweigh the promise of potential benefit, which must now be tested in definitive clinical trials.…”

Section: Vascular Regeneration In Padmentioning

confidence: 99%

Clinical Trials of Adult Stem Cell Therapy for Peripheral Artery Disease

Botham

Bennett

Cooke

2013

Methodist DeBakey Cardiovascular Journal

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“…[75][76][77] MSCs are another population frequently used in clinical trials, sourced from various tissues including bone marrow, adipose tissue, and the umbilical cord. SVF represents an additional collection of progenitor cells, including MSCs and EPCs.…”

mentioning

confidence: 99%

Stem cells and chronic wound healing: state of the art

Leavitt¹,

Hu²,

Barnes³

et al. 2016

CWCMR

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Currently available treatments for chronic wounds are inadequate. A clearly effective therapy does not exist, and treatment is often supportive. This is largely because the cellular and molecular processes underlying failure of wound repair are still poorly understood. With an increase in comorbidities, such as diabetes and vascular disease, as well as an aging population, the incidence of these intractable wounds is expected to rise. As such, chronic wounds, which are already costly, are rapidly growing as a tremendous burden to the health-care system. Stem cells have garnered much interest as a therapy for chronic wounds due to their inherent ability to differentiate into multiple lineages and promote regeneration. Herein, we discuss the types of stem cells used for chronic wound therapy, as well as the proposed means by which they do so. In particular, we highlight mesenchymal stem cells (including adipose-derived stem cells), endothelial progenitor cells, and induced pluripotent stem cells. We include the results of recent in vitro and in vivo studies in both animal models and human clinical trials. Finally, we discuss the current studies to improve stem cell therapies and the limitations of stem cell-based therapeutics. Stem cells promise improved therapies for healing chronic wounds, but further studies that are well-designed with standardized protocols are necessary for fruition.

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Cellular Therapy With Ixmyelocel-T to Treat Critical Limb Ischemia: The Randomized, Double-blind, Placebo-controlled RESTORE-CLI Trial

Cited by 136 publications

References 16 publications

Effect of Repetitive Intra-Arterial Infusion of Bone Marrow Mononuclear Cells in Patients With No-Option Limb Ischemia

Effect of Repetitive Intra-Arterial Infusion of Bone Marrow Mononuclear Cells in Patients With No-Option Limb Ischemia

Clinical Trials of Adult Stem Cell Therapy for Peripheral Artery Disease

Stem cells and chronic wound healing: state of the art

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