Stem cells therapy in acute myocardial infarction: a new era?

Carbone, Roberto; Monselise, Assaf; Bottino, Giovanni; Negrini, Simone; Puppo, Francesco

doi:10.1007/s10238-021-00682-3

Cited by 20 publications

(22 citation statements)

References 57 publications

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“…In most stem cell-treated AMI trials, transplanted cells were BMNCs and the benefits in cardiac regeneration were mixed and uncertain ( 10 ). To date, the autologous bone marrow cell therapy in AMI trial (BAMI) is the largest study of stem-based cell therapy for AMI in the world.…”

Section: Discussionmentioning

confidence: 99%

First-in-human pilot trial of combined intracoronary and intravenous mesenchymal stem cell therapy in acute myocardial infarction

Hsiao

Lin

Shyu

et al. 2022

Front. Cardiovasc. Med.

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BackgroundAcute ST-elevation myocardial infarction (STEMI) elicits a robust cardiomyocyte death and inflammatory responses despite timely revascularization.ObjectivesThis phase 1, open-label, single-arm, first-in-human study aimed to assess the safety and efficacy of combined intracoronary (IC) and intravenous (IV) transplantation of umbilical cord-derived mesenchymal stem cells (UMSC01) for heart repair in STEMI patients with impaired left ventricular ejection fraction (LVEF 30-49%) following successful reperfusion by percutaneous coronary intervention.MethodsConsenting patients received the first dose of UMSC01 through IC injection 4-5 days after STEMI followed by the second dose of UMSC01 via IV infusion 2 days later. The primary endpoint was occurrence of any treatment-related adverse events and the secondary endpoint was changes of serum biomarkers and heart function by cardiac magnetic resonance imaging during a 12-month follow-up period.ResultsEight patients gave informed consents, of whom six completed the study. None of the subjects experienced treatment-related serious adverse events or major adverse cardiovascular events during IC or IV infusion of UMSC01 and during the follow-up period. The NT-proBNP level decreased (1362 ± 1801 vs. 109 ± 115 pg/mL, p = 0.0313), the LVEF increased (52.67 ± 12.75% vs. 62.47 ± 17.35%, p = 0.0246), and the wall motion score decreased (26.33 ± 5.57 vs. 22.33 ± 5.85, p = 0.0180) at the 12-month follow-up compared to the baseline values. The serial changes of LVEF were 0.67 ± 3.98, 8.09 ± 6.18, 9.04 ± 10.91, and 9.80 ± 7.56 at 1, 3, 6, and 12 months, respectively as compared to the baseline.ConclusionThis pilot study shows that combined IC and IV transplantation of UMSC01 in STEMI patients with impaired LVEF appears to be safe, feasible, and potentially beneficial in improving heart function. Further phase 2 studies are required to explore the effectiveness of dual-route transplantation of UMSC01 in STEMI patients.

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Section: Discussionmentioning

confidence: 99%

First-in-human pilot trial of combined intracoronary and intravenous mesenchymal stem cell therapy in acute myocardial infarction

Hsiao

Lin

Shyu

et al. 2022

Front. Cardiovasc. Med.

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“…Cells of extracardiac origin were shown to home to the injured myocardium and contribute to repair via an effect on angiogenesis and inflammation [2,3]. Seeing this potential marked the onset of the quest for CVD cell-based therapy, which has shown to have some beneficial effects [2,3,5,6 ▪▪ ,7 ▪▪ ]. Yet, it depends on both cell type and the extent of cell retention and survival.…”

Section: Cell-based Therapiesmentioning

confidence: 99%

“…PreSERVE-AMI found an effect only upon adjustment for ischemia time [5]. The MI cell-based therapy therefore does not seem to be thoroughly convincing, and the pros and cons are summarized elsewhere [6 ▪▪ ]. Optimization steps such as cell preconditioning or genetic modifications are being studied to enhance cell properties (reviewed in [7 ▪▪ ]).…”

Section: Cell-based Therapiesmentioning

confidence: 99%

Building new cardiac vasculature and myocardium: where are we at?

Sedláková

Ahumada

Suuronen

et al. 2021

Current Opinion in Cardiology

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Purpose of reviewThis review describes the latest advances in cell therapy, biomaterials and 3D bioprinting for the treatment of cardiovascular disease.Recent findingsCell therapies offer the greatest benefit for patients suffering from chronic ischemic and nonischemic cardiomyopathy. Rather than replacing lost cardiomyocytes, the effects of most cell therapies are mediated by paracrine signalling, mainly through the induction of angiogenesis and immunomodulation. Cell preconditioning, or genetic modifications are being studied to improve the outcomes. Biomaterials offer stand-alone benefits such as bioactive cues for cell survival, proliferation and differentiation, induction of vascularization or prevention of further cardiomyocyte death. They also provide mechanical support or electroconductivity, and can be used to deliver cells, growth factors or drugs to the injured site. Apart from classical biomaterial manufacturing techniques, 3D bioprinting offers greater spatial control over biomaterial deposition and higher resolution of the details, including hollow vessel-like structures.SummaryCell therapy induces mainly angiogenesis and immunomodulation. The ability to induce direct cardiomyocyte regeneration to replace the lost cardiomyocytes is, however, still missing until embryonic or induced pluripotent stem cell use becomes available. Cell therapy would benefit from combinatorial use with biomaterials, as these can prolong cell retention and survival, offer additional mechanical support and provide inherent bioactive cues. Biomaterials can also be used to deliver growth factors, drugs, and other molecules. 3D bioprinting is a high-resolution technique that has great potential in cardiac therapy.

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“…Stem cell therapy in patients with AMI was introduced as putative treatment in repairing the damaged myocardium. So far, multipotent stem cells from different sources, such as bone marrow-derived stem cells, circulating progenitor cells, and mesenchymal cells, have been employed for transplantation which can be delivered through different routes [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…It has been shown that cell therapy of the infarcted myocardium can promote regeneration of the cardiomyocytes and angiogenic capacity by producing different paracrine factors [ 5 ]. Among different kinds of cells, bone marrow mononuclear cells (BM-MNCs) and mesenchymal stem cells (MSCs) are the most frequently explored stem cells in trials exploring the potential regenerative effects of stem cells on injured myocardial tissue in AMI patients [ 4 ]. Autologous administration of stem cells in humans for assessing their effects on cardiac function in AMI was first appeared in a study at 2001 by Strauer et al which showed improvement in ejection fraction (LVEF) and reduction in scar size [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Comparing the effect of bone marrow mono-nuclear cells with mesenchymal stem cells after acute myocardial infarction on improvement of left ventricular function: a meta-analysis of clinical trials

et al. 2022

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Background The effect of transplantation of bone-marrow mononuclear cells (BM-MNCs) and mesenchymal stem cells (MSCs) on ejection fraction (LVEF) has been studied in patients with acute myocardial infarction (AMI) in clinical trials. This raises the question that which type of cell may help improve LVEF better in AMI patients. No meta-analysis of clinical trials has yet addressed this question. Methods Electronic databases were searched thoroughly to find eligible trials on the effects of transplantation of BM-MNCs and MSCs in patients with AMI. The primary outcome was improvement in LVEF. Data were synthesized using random-effects meta-analysis. For maximizing the credibility of subgroup analysis, we used the instrument for assessing the Credibility of Effect Modification of Analyses (ICEMAN) for meta-analyses. Results A total of 36 trials (26 on BM-MNCs and 10 on MSCs) with 2489 patients (1466 were transplanted [1241 with BM-MNCs and 225 with MSCs] and 1023 as controls) were included. Both types of cells showed significant improvements in ejection fraction in short-term follow-up (BM-MNCs: WMD = 2.13%, 95% CI = 1.23 to 3.04, p < 0.001; MSCs: WMD = 3.71%, 95% CI = 2.32 to 5.09, p < 0.001), and according to ICEMAN criteria, MSCs are more effective. For selected population of patients who received stem cell transplantation in early course after AMI (less than 11 days), this effect was even more pronounced (BM-MNC: WMD = 3.07%, 95% CI = 1.97 to 4.17, p < 0.001, I2 = 40.7%; MSCs: WMD = 5.65%, 95% CI = 3.47 to 7.84, p < 0.001, I2 = 84.6%). Conclusion Our results showed that transplantation of MSCs after AMI might increase LVEF more than BM-MNCs; also, based on ICEMAN, there was likely effect modification between subgroups although uncertainty still remained.

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Stem cells therapy in acute myocardial infarction: a new era?

Cited by 20 publications

References 57 publications

First-in-human pilot trial of combined intracoronary and intravenous mesenchymal stem cell therapy in acute myocardial infarction

First-in-human pilot trial of combined intracoronary and intravenous mesenchymal stem cell therapy in acute myocardial infarction

Building new cardiac vasculature and myocardium: where are we at?

Comparing the effect of bone marrow mono-nuclear cells with mesenchymal stem cells after acute myocardial infarction on improvement of left ventricular function: a meta-analysis of clinical trials

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