Intracoronary autologous bone marrow cell transfer after myocardial infarction: the BOOST-2 randomised placebo-controlled clinical trial

Wollert, Kai C.; Meyer, Gerd Peter; Müller‐Ehmsen, Jochen; Tschöpe, Carsten; Bonarjee, Vernon; Larsen, Alf Inge; May, Andreas E.; Empen, Klaus; Chorianopoulos, Emmanuel; Tebbe, Ulrich; Waltenberger, Johannes; Mahrholdt, Heiko; Ritter, Benedikta; Pirr, Jens; Fischer, Dieter; Korf‐Klingebiel, Mortimer; Arseniev, Lubomir; Heuft, Hans‐Gert; Brinchmann, Jan E.; Messinger, Diethelm; Hertenstein, Bernd; Ganser, Arnold; Katus, Hugo A.; Felix, Stephan B.; Gawaz, Meinrad; Dickstein, Kenneth; Schultheiss, Heinz‐Peter; Ladage, Dennis; Greulich, Simon; Bauersachs, Johann

doi:10.1093/eurheartj/ehx188

Cited by 99 publications

(64 citation statements)

References 23 publications

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“…If the difference between the different treatment groups was 4.5%, the bilateral test was carried out at a signi cant level of α = 0.05, and the test e cacy reached 80%. To draw a conclusion that the difference was statistically signi cant, then 34 patients were required in each group [22] . During the implementation of this study, it was discovered that although the researchers explained in detail to the patients that the extraction of bone marrow had no adverse effects on the body, the patient had an instinctive fear of taking bone marrow, and they were very resistant.…”

Section: Discussionmentioning

confidence: 99%

Bone marrow mesenchymal stem cells transfer in patients with ST-segment elevation myocardial infarction: single-blind, randomized controlled muticentre trial

Zhang

Jiang

Zhang³

et al. 2020

Preprint

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Objective: Our aimed to evaluate efficacy and safety of intracoronary autologous bone morrow mesenchymal stem cells (BM-MSCs) transplantation in patients with ST-segment elevation myocardial infarction（STEMI）. Methods: In this randomised, single-blind, controlled trial, patients with STEMI (aged 39-76 years) were enrolled at 6 centers in Beijing (the People's Liberation Army Navy General Hospital, Beijing Armed Police General Hospital, Chinese People's Liberation Army General Hospital, Beijing Huaxin Hospital, Beijing Tongren Hospital, Beijing Chaoyang Hospital West Hospital). Patients underwent optimum medical treatment and percutaneous coronary intervention,and were randomly assigned in a 1:1 ratio to BM-MSCs group or control group. The primary endpoint was change of myocardial viability at 6 months' follow-up and left-ventricular (LV) function at 12 months' follow-up.The secondary endpoints were incidence of cardiovascular event, total mortality and adverse event at 12 months' follow-up. The myocardial viability assessed by single- photon emission tomography (SPECT). The left ventricular ejection fraction was used to assess LV function. All patients underwent dynamic ECG and laboratory evaluations. This trial is registered with ClinicalTrails.gov, number NCT04421274. Results: Between March , 2008, and July , 2010, 43 patients were randomly assigned to BM-MSCs group (n=21)or control group(n=22) and followed up for 12 months. LV ejection fraction increased from baseline to 12 months in the BM-MSCs group and control group ( mean baseline-adjusted BM-MSCs treatment differences in LV ejection fraction 4.8% (SD 9.0) and mean baseline-adjusted control group treatment differences in LV ejection fraction 5.8% (SD 6.04) ). After 6 months of follow-up, there was no significant improvement in myocardial metabolic activity in the BM-MSCs group before and after transplantation. however,there was no statistically significant difference between the two groups in the change of LV ejection fraction (p=0.30) and myocardial metabolic activity(p>0.05). We noticed that ,after 12 months of follow-up, except for 1 death and 1 coronary microvascular embolism in the BM-MSCs group, no other events occurred and Alanine transaminase(ALT) and C-reactive protein(CRP) in BM-MSCs group were significantly lower than that in control group. Conclusions: It is unreasonable to speculate that intracoronary transfer of autologous bone marrow MSCs could augment recovery of LV function and myocardial viability after acute myocardial infarction.Trial registration: clinicaltrials,NCT04421274. Registered 06,08,2020- Retrospectively registered, https://register.clinicaltrials.gov/NCT04421274.

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Section: Discussionmentioning

confidence: 99%

Bone marrow mesenchymal stem cells transfer in patients with ST-segment elevation myocardial infarction: single-blind, randomized controlled muticentre trial

Zhang

Jiang

Zhang³

et al. 2020

Preprint

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“…BM-MNC therapy has been initiated for limb ischemia and in ischemic wound healing with angiographic findings and physiological parameters being reported. 23 However, nonresponders to cell therapy exist 24,25 and both positive 26,27 and neutral/negative 28,29 results have been reported in double blinded, placebo-controlled studies using autologous BM-MNC transplantation for myocardial infarction. The reasons of the contradictory results are currently unclear.…”

Section: Discussionmentioning

confidence: 99%

Clot-Derived Contaminants in Transplanted Bone Marrow Mononuclear Cells Impair the Therapeutic Effect in Stroke

Okinaka

Kikuchi-Taura

Takeuchi

et al. 2019

Stroke

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Background and Purpose— The beneficial effects of bone marrow mononuclear cell (BM-MNC) transplantation in preclinical experimental stroke have been reliably demonstrated. However, only overall modest effects in clinical trials were observed. We have investigated and reported a cause of the discrepancy between the preclinical and clinical studies. Methods— To investigate the possible cause of low efficacy of BM-MNC transplantation in experimental stroke, we have focused on blood clot formation, which is not uncommon in human bone marrow aspirates. To evaluate the effects of clot-derived contaminants in transplanted BM-MNC on stroke outcome, a murine stroke model was used. Results— We show that BM-MNC separated by an automatic cell isolator (Sepax2), which does not have the ability to remove clots, did not attenuate brain atrophy after stroke. In contrast, manually isolated, clot-free BM-MNC exerted therapeutic effects. Clot-derived contaminants were also transplanted intravenously to poststroke mice. We found that the transplanted contaminants were trapped at the peristroke area, which were associated with microglial/macrophage activation. Conclusions— Clot-derived contaminants in transplanted BM-MNC nullify therapeutic effects in experimental stroke. This may explain neutral results in clinical trials, especially in those using automated stem cell separators that lack the ability to remove clot-derived contaminants. Visual Overview— An online visual overview is available for this article.

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“…For example, intracoronary delivery of autologous stem/progenitor cells (SPCs) is a promising adjuvant therapeutic strategy to improve LV function for patients with acute myocardial infarction (AMI) [7,8]. However, published data from clinical trials conducted so far showed inconsistent results in regard to the effectiveness of stem cell-based therapy [9][10][11][12][13][14]. Our understanding of pathomechanisms of stem cell-based therapy is still limited.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Intracoronary Infusion of Autologous Bone Marrow-Derived Lineage-Negative Stem/Progenitor Cells on Remodeling of Post-Infarcted Heart in Patient with Acute Myocardial Infarction

Peregud‐Pogorzelska¹,

Przybycień²,

Baumert³

et al. 2020

Int. J. Med. Sci.

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Introduction: Regenerative capacity of the heart is limited, and the post-infarct left ventricle (LV) dysfunction is associated with poor prognosis. Administration of stem/progenitor cells (SPCs) is a promising approach for cardiac regeneration. Objectives: In the study, we assessed LV function and post-infarcted remodeling in patients with ST-elevated myocardial infarct (STEMI) who received autologous lineage-negative (LIN -) SPCs. Patients and methods: Patients with STEMI and one-vessel coronary artery disease treated with percutaneous revascularisation were divided into study group (LINgroup, 15 patients) that received standard therapy and autologous BM-derived LIN -SPCs and control group (standard therapy group, 19 patients). The cells were administered intracoronary 24 hours after STEMI. The follow-up was 12 months with subsequent non-invasive tests and laboratory parameter evaluation on days 1 st , 3 rd , and 7 th as well as at 1 st , 3 rd , 6 th and 12 th month after STEMI. Results: All procedures related to SPCs administration were well tolerated by the patients. In 12-month follow-up, there were no major adverse cardiac events connected with LIN -SPCs administration. During 12-month follow-up, 9 patients from LINgroup (Responders) achieved an improvement in LV ejection fraction (>10% after 12 months) with no signs of unfavorable LV remodeling. Laboratory parameters analysis showed that Troponin T levels were significantly lower until day 7 th in the Responders group, while brain natriuretic peptide (BNP) level remained significantly lower from day 3 rd to 12 th month respectively. Conclusions: Intracoronary infusion of autologous BM-derived LINstem/progenitor cells is feasible and safe for patient. Improvement in LV function and prevention of unfavorable remodeling in the 60% of study group seems relatively promising. Stem cell-based therapy for cardiac regeneration still needs more accurate and extensive investigations to estimate and improve their efficacy.

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Intracoronary autologous bone marrow cell transfer after myocardial infarction: the BOOST-2 randomised placebo-controlled clinical trial

Cited by 99 publications

References 23 publications

Bone marrow mesenchymal stem cells transfer in patients with ST-segment elevation myocardial infarction: single-blind, randomized controlled muticentre trial

Bone marrow mesenchymal stem cells transfer in patients with ST-segment elevation myocardial infarction: single-blind, randomized controlled muticentre trial

Clot-Derived Contaminants in Transplanted Bone Marrow Mononuclear Cells Impair the Therapeutic Effect in Stroke

The Effect of Intracoronary Infusion of Autologous Bone Marrow-Derived Lineage-Negative Stem/Progenitor Cells on Remodeling of Post-Infarcted Heart in Patient with Acute Myocardial Infarction

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