Improved outcome with repeated intracoronary injection of bone marrow-derived cells within a registry: rationale for the randomized outcome trial REPEAT

Aßmus, Birgit; Alakmeh, Samer; Rosa, Salvatore De; Bönig, Halvard; Hermann, Eva; Levy, Wayne C.; Dimmeler, Stefanie; Zeiher, Andreas M.

doi:10.1093/eurheartj/ehv559

Cited by 40 publications

(22 citation statements)

References 25 publications

(25 reference statements)

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“…For post-infarction ischemic cardiomyopathy, the REPEAT (REpetitive Progenitor cEll therapy in Advanced chronic hearT failure, NCT01693042), is a multicenter, open-label, randomized controlled trial of 676 patients comparing single vs. repeat intracoronary infusion of BM-MNCs powered for all-cause mortality, with completion anticipated in 2025 after a 2-year minimum follow-up. 106 If the BAMI and REPEAT trials are successfully completed, their outcomes will hopefully definitively answer the efficacy of BM-MNCs in acute MI and ischemic cardiomyopathy, respectively.…”

Section: Cardiosphere-derived Cellsmentioning

confidence: 99%

Function Follows Form　― A Review of Cardiac Cell Therapy ―

Nakamura

Murry

2019

Circ J

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The investment of nearly 2 decades of clinical investigation into cardiac cell therapy has yet to change cardiovascular practice. Recent insights into the mechanism of cardiac regeneration help explain these results and provide important context in which we can develop next-generation therapies. Non-contractile cells such as bone marrow or adult heart derivatives neither engraft long-term nor induce new muscle formation. Correspondingly, these cells offer little functional benefit to infarct patients. In contrast, preclinical data indicate that transplantation of bona fide cardiomyocytes derived from pluripotent stem cells induces direct remuscularization. This new myocardium beats synchronously with the host heart and induces substantial contractile benefits in macaque monkeys, suggesting that regeneration of contractile myocardium is required to fully recover function. Through a review of the preclinical and clinical trials of cardiac cell therapy, distinguishing the primary mechanism of benefit as either contractile or non-contractile helps appreciate the barriers to cardiac repair and establishes a rational path to optimizing therapeutic benefit.

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Section: Cardiosphere-derived Cellsmentioning

confidence: 99%

Function Follows Form　― A Review of Cardiac Cell Therapy ―

Nakamura

Murry

2019

Circ J

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“…Th is treatment still did not become a standard for CAD patients, despite several meta-analyses have shown some benefi ts of the cellular therapy [18][19][20] Over At the present time, upon additional analysis and further controlled studies, we conclude that the most positive eff ects of the cellular therapy could be explained by neoangiogenesis which could be observed following an eff ective cellular therapy. Most workers agree that a paracrine mechanism for the cytokine action is predominant under these conditions [24]. However, intercellular relations are known to be mediated by the cytokine eff ects.…”

Section: Clinical Evidencementioning

confidence: 99%

“…A successful experience with repeated injections of BM MNCs was also published by a group of workers from Frankfurt [24]. Th e authors used intracoronary injections of autologous bone marrow-derived mononuclear cells (BM-MNCs).…”

Section: Dilated Cardiomyopathymentioning

confidence: 99%

Does the local coronary endothelial dysfunction exist? Potential implications for cardiac cellular therapy

Немков¹,

Zhang²

2017

CTT

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Endothelium is a cellular layer lining blood vessels in either a human organ or tissue. For decades, protective and barrier functions were considered to be the main property of vascular endothelium. Over last 20 years, however, endothelium is also considered an active endocrine organ which, due to secretion of multiple enzymes, metabolic and growth factors, may exert suffi cient regulatory eff ects upon heart and blood vessels, thus playing an important role in pathogenesis of certain cardiovascular disorders. Accumulating data on changing interactions between heart vascular endothelium and myocardium allow us to suggest an additional local function for coronary endothelium, i.e., a proposed production of biologically active substances by endothelial cells, and their eff ects upon metabolism, functioning, survival and regeneration of cardiomyocytes. Th e discussion article presents analysis of distinct studies concerning cellular therapy in human heart diseases. Th ese data are favoring a hypothesis about additional role of endothelium in cardiac function, and off er a potential ability to correct endothelial dysfunction by means of cellular therapy.

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“…Consistently, in the CCTRN TIME (Cardiovascular Cell Therapy Research Network Timing in Myocardial Infarction Evaluation) trial, administration of a higher percentage of CD45 + CD31 low bone marrow-derived single cells resulted in significantly reduced infarct size at 6 months after cell therapy. 11 Recently, several studies have reported that repeated injections of bone marrow-derived cells significantly improve LV function and long-term survival 12,13.…”

mentioning

confidence: 99%

Insights From 10-Year Outcomes of Mesenchymal Stem Cell Transplantation in Heart Failure Patients

Inoue

Takamura

2019

Circ J

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cardiac function in rodents. 2 Since the mid-2000 s, clinical trials, including randomized controlled trials (RCTs), using bone marrow-derived MSCs (BMMSCs) have been conducted. 3 A meta-analysis of cell therapy studies using bone marrow-derived cells, including BMMSCs (50 studies, 2,625 recipients) demonstrated that patients receiving cell therapy resulted in improvement of LV function with greater EF (+3.96%), reduced infarct size, and smaller LV volume. 4

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Improved outcome with repeated intracoronary injection of bone marrow-derived cells within a registry: rationale for the randomized outcome trial REPEAT

Cited by 40 publications

References 25 publications

Function Follows Form　― A Review of Cardiac Cell Therapy ―

Function Follows Form　― A Review of Cardiac Cell Therapy ―

Does the local coronary endothelial dysfunction exist? Potential implications for cardiac cellular therapy

Insights From 10-Year Outcomes of Mesenchymal Stem Cell Transplantation in Heart Failure Patients

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Improved outcome with repeated intracoronary injection of bone marrow-derived cells within a registry: rationale for the randomized outcome trial REPEAT

Cited by 40 publications

References 25 publications

Function Follows Form ― A Review of Cardiac Cell Therapy ―

Function Follows Form ― A Review of Cardiac Cell Therapy ―

Does the local coronary endothelial dysfunction exist? Potential implications for cardiac cellular therapy

Insights From 10-Year Outcomes of Mesenchymal Stem Cell Transplantation in Heart Failure Patients

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Product

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Function Follows Form　― A Review of Cardiac Cell Therapy ―

Function Follows Form　― A Review of Cardiac Cell Therapy ―