Intramyocardial Stem Cell Transplantation during Coronary Artery Bypass Surgery Safely Improves Cardiac Function: Meta-Analysis of 20 Randomized Clinical Trials

Soetisna, Tri Wisesa; Thamrin, Ahmad Muslim Hidayat; Permadijana, Diajeng; Ramadhani, Andi Nurul Erisya; Sugisman,; Santoso, Anwar; Mansyur, Muchtaruddin

doi:10.3390/jcm12134430

Cited by 4 publications

(2 citation statements)

References 32 publications

(205 reference statements)

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“…Also, there was no significant improvement in LVEF, 6MWD, and pro-BNP levels compared to the baseline. These data contradict a meta-analysis by Soetisna et al [ 31 ], which reported an increase in the 6MWD in patients with ischemic heart disease treated. Nevertheless, apart from suggested efficacy limitations in our findings, one of the significant drawbacks to implementing the TEPI RoD is its invasive nature, which may also lead to perforation and arrhythmia.…”

Section: Discussioncontrasting

confidence: 98%

Establishing delivery route-dependent safety and efficacy of living biodrug mesenchymal stem cells in heart failure patients

Jihwaprani,

Sula,

Charbat

et al. 2024

World J Cardiol

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BACKGROUND Mesenchymal stem cells (MSCs) as living biopharmaceuticals with unique properties, i.e. , stemness, viability, phenotypes, paracrine activity, etc. , need to be administered such that they reach the target site, maintaining these properties unchanged and are retained at the injury site to participate in the repair process. Route of delivery (RoD) remains one of the critical determinants of safety and efficacy. This study elucidates the safety and effectiveness of different RoDs of MSC treatment in heart failure (HF) based on phase II randomized clinical trials (RCTs). We hypothesize that the RoD modulates the safety and efficacy of MSC-based therapy and determines the outcome of the intervention. AIM To investigate the effect of RoD of MSCs on safety and efficacy in HF patients. METHODS RCTs were retrieved from six databases. Safety endpoints included mortality and serious adverse events (SAEs), while efficacy outcomes encompassed changes in left ventricular ejection fraction (LVEF), 6-minute walk distance (6MWD), and pro-B-type natriuretic peptide (pro-BNP). Subgroup analyses on RoD were performed for all study endpoints. RESULTS Twelve RCTs were included. Overall, MSC therapy demonstrated a significant decrease in mortality [relative risk (RR): 0.55, 95% confidence interval (95%CI): 0.33-0.92, P = 0.02] compared to control, while SAE outcomes showed no significant difference (RR: 0.84, 95%CI: 0.66-1.05, P = 0.11). RoD subgroup analysis revealed a significant difference in SAE among the transendocardial (TESI) injection subgroup (RR = 0.71, 95%CI: 0.54-0.95, P = 0.04). The pooled weighted mean difference (WMD) demonstrated an overall significant improvement of LVEF by 2.44% (WMD: 2.44%, 95%CI: 0.80-4.29, P value ≤ 0.001), with only intracoronary (IC) subgroup showing significant improvement (WMD: 7.26%, 95%CI: 5.61-8.92, P ≤ 0.001). Furthermore, the IC delivery route significantly improved 6MWD by 115 m (WMD = 114.99 m, 95%CI: 91.48-138.50), respectively. In biochemical efficacy outcomes, only the IC subgroup showed a significant reduction in pro-BNP by -860.64 pg/mL (WMD: -860.64 pg/Ml, 95%CI: -944.02 to -777.26, P = 0.001). CONCLUSION Our study concluded that all delivery methods of MSC-based therapy are safe. Despite the overall benefits in efficacy, the TESI and IC routes provided better outcomes than other methods. Larger-scale trials are warranted before implementing MSC-based therapy in routine clinical practice.

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Section: Discussioncontrasting

confidence: 98%

Establishing delivery route-dependent safety and efficacy of living biodrug mesenchymal stem cells in heart failure patients

Jihwaprani,

Sula,

Charbat

et al. 2024

World J Cardiol

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“…A systemic review and meta-analysis in 2015, which included 48 randomized controlled trials recruiting 2602 patients diagnosed with either chronic ischemic heart disease or myocardial infarction, demonstrated an improvement in left ventricular ejection fraction and the suppression of myocardial remodeling in those undergoing adult bone marrow cell therapies [51]. In addition, a recent meta-analysis of 20 randomized controlled trials on the outcome and safety of intramyocardial stem cell transplantation during coronary artery bypass surgery reported a significant improvement in left ventricular ejection fraction and wall motion without increasing risk in patients receiving cell therapy compared to controls [52], thereby further supporting the significant therapeutic benefits of stem cell application in the treatment of ischemic heart disease.…”

Section: Acute and Chronic Coronary Syndromesmentioning

confidence: 99%

Stem Cell Therapy against Ischemic Heart Disease

Tsai,

Sun

2024

IJMS

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Ischemic heart disease, which is one of the top killers worldwide, encompasses a series of heart problems stemming from a compromised coronary blood supply to the myocardium. The severity of the disease ranges from an unstable manifestation of ischemic symptoms, such as unstable angina, to myocardial death, that is, the immediate life-threatening condition of myocardial infarction. Even though patients may survive myocardial infarction, the resulting ischemia-reperfusion injury triggers a cascade of inflammatory reactions and oxidative stress that poses a significant threat to myocardial function following successful revascularization. Moreover, despite evidence suggesting the presence of cardiac stem cells, the fact that cardiomyocytes are terminally differentiated and cannot significantly regenerate after injury accounts for the subsequent progression to ischemic cardiomyopathy and ischemic heart failure, despite the current advancements in cardiac medicine. In the last two decades, researchers have realized the possibility of utilizing stem cell plasticity for therapeutic purposes. Indeed, stem cells of different origin, such as bone-marrow- and adipose-derived mesenchymal stem cells, circulation-derived progenitor cells, and induced pluripotent stem cells, have all been shown to play therapeutic roles in ischemic heart disease. In addition, the discovery of stem-cell-associated paracrine effects has triggered intense investigations into the actions of exosomes. Notwithstanding the seemingly promising outcomes from both experimental and clinical studies regarding the therapeutic use of stem cells against ischemic heart disease, positive results from fraud or false data interpretation need to be taken into consideration. The current review is aimed at overviewing the therapeutic application of stem cells in different categories of ischemic heart disease, including relevant experimental and clinical outcomes, as well as the proposed mechanisms underpinning such observations.

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Transendocardial injection of expanded autologous CD34+ cells after myocardial infarction: Design of the EXCELLENT trial

Roncalli,

Roubille,

Meyer

et al. 2024

ESC Heart Failure

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AimsThe extent of irreversible cardiomyocyte necrosis after acute myocardial infarction (AMI) is a major determinant of residual left ventricular (LV) function and clinical outcome. Cell therapy based on CD34+ cells has emerged as an option to help repair the myocardium and to improve outcomes. The dose of CD34+ cells and the route of administration are two important factors that will determine the clinical effectiveness of the approach, provided it is robust and feasible. Here, we describe the rationale and design of the multicentre open‐label randomized controlled phase I/IIb trial evaluating the safety and the likelihood of efficacy of transendocardial expanded CD34+ cell administration in patients presenting with AMI and a reduced LV ejection fraction.MethodsPatients with a large AMI and LV ejection fraction <50% are randomized 3:1 to transendocardial expanded CD34+ cell injection plus standard of care or standard of care alone. Patients randomized to intervention are treated with lenograstim for 5 days before 220 ± 10 mL blood cell harvest from which autologous CD34+ cells are purified and expanded for 9 days using an automated good manufacturing practice compliant platform. The primary endpoint is the incidence of major adverse cardiac events over 6 months. The main secondary endpoints are LV end systolic volume index and the viability of the infarcted segments.ConclusionsAutologous CD34+ cell therapy is currently limited by technological constraints. This is the first trial to evaluate the feasibility and potential effect of CD34+ cells after automated expansion and transendocardial administration in patients with large AMI.

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Intramyocardial Stem Cell Transplantation during Coronary Artery Bypass Surgery Safely Improves Cardiac Function: Meta-Analysis of 20 Randomized Clinical Trials

Cited by 4 publications

References 32 publications

Establishing delivery route-dependent safety and efficacy of living biodrug mesenchymal stem cells in heart failure patients

Establishing delivery route-dependent safety and efficacy of living biodrug mesenchymal stem cells in heart failure patients

Stem Cell Therapy against Ischemic Heart Disease

Transendocardial injection of expanded autologous CD34+ cells after myocardial infarction: Design of the EXCELLENT trial

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