Cardiac Stem Cell Treatment in Myocardial Infarction: A Systematic Review and Meta-Analysis of Preclinical Studies (original) (raw)
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Stem Cells Improve Left Ventricular Function in Acute Myocardial Infarction
Clinical Cardiology, 2009
Background: Animal studies have suggested dramatic improvement in cardiac function after acute myocardial infarction (AMI) through regeneration of the myocardium or neovascularization by transfer of cells derived from bone marrow (BMC) generated clinical studies. Recently published small sized studies have yielded mixed results, leaving the question unanswered. Hypothesis: We analyzed data from these studies in a meta-analysis to investigate if intracoronary stem cell therapy was effective in improving cardiac function. Methods: A total of 7 randomized controlled trials meeting the inclusion criteria were identified by a systematic literature search. Primary endpoint was change in global left ventricular ejection fraction (LVEF) baseline to follow-up (ranging between 3 to 6 months). The meta-analysis consisted of 516 patients (BMC group, 256; control group, 260). A 2-sided α error of less than .05 was considered to be statistically significant (P<.05).
Animals, 2022
Stem-cell therapy provides a promising strategy for patients with ischemic heart disease. In recent years, numerous studies related to this therapeutic approach were performed; however, the results were often heterogeneous and contradictory. For this reason, we conducted a systematic review and meta-analysis of trials, reporting the use of stem-cell treatment against acute or chronic ischemic cardiomyopathies in large animal models with regard to Left Ventricular Ejection Fraction (LVEF). The defined research strategy was applied to the PubMed database to identify relevant studies published from January 2011 to July 2021. A random-effect meta-analysis was performed on LVEF mean data at follow-up between control and stem-cell-treated animals. In order to improve the definition of the effect measure and to analyze the factors that could influence the outcomes, a subgroup comparison was conducted. Sixty-six studies (n = 1183 animals) satisfied our inclusion criteria. Ischemia/reperfusi...
The Indian journal of medical research, 2015
Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 × 10 [8] autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy. In this phase III prospective, multicentric trial 250 patient...
New directions in cardiac stem cell therapy: An update for clinicians
World Journal of Cardiovascular Diseases, 2012
The emergence of cardiac stem cell therapy can be traced to late 2001, when studies in small animal models of myocardial infarction suggested that stem cells could engraft, proliferate, and regenerate myocardium. Subsequent animal laboratory studies showed improved cardiac function, perfusion and survival compared to controls (Figure 1). Within two years, the first clinical trials of stem cell therapy began to appear, and we now have several trials of intracoronary infusion of bone marrow cells with more than one year follow-up. Although this clinical therapy has proven to be safe, the magnitude of improvement in objective measures like ejection fraction has been modest, and the therapy has not entered clinical practice. In the absence of a large prospective randomized trial, the field has moved back to the laboratory. This manuscript aims to provide clinicians with a broad overview of this complex field by briefly reviewing the existing status of clinical myocardial regeneration therapy, then describing selected examples from the laboratory research approaches that may provide a platform for new and potentially increasingly effective clinical strategies.
Circulation: Cardiovascular Interventions, 2014
Background-Several cell-based therapies for adjunctive treatment of acute myocardial infarction have been investigated in multiple clinical trials, but the benefits still remain controversial. This meta-analysis aims to evaluate the efficacy of bone marrow-derived mononuclear cell (BMMNC) therapy in patients with acute myocardial infarction, but also explores the effect of newer generations of stem cells. Methods and Results-A random-effects meta-analysis was performed on randomized controlled trials investigating the effects of stem cell therapy in patients with acute myocardial infarction that were published between January 2002 and September 2013. The defined end points were left ventricular (LV) ejection fraction, LV end-systolic and end-diastolic volumes, infarct size, and major adverse cardiac and cerebrovascular event rates. Also, several subgroup analyses were performed on BMMNC trials. Overall, combining the results of 22 randomized controlled trials (RCTs), LV ejection fraction increased by +2.10% (95% confidence interval [CI], 0.68-3.52; P=0.004) in the BMMNC group as compared with controls, evoked by a preservation of LV end-systolic volume (−4.05 mL; 95% CI, −6.91 to −1.18; P=0.006) and a reduction in infarct size (−2.69%; 95% CI, −4.83 to −0.56; P=0.01). However, there is no effect on cardiac function, volumes, or infarct size, when only RCTs (n=9) that used MRI-derived end points were analyzed. Moreover, no beneficial effect could be detected on major adverse cardiac and cerebrovascular event rates after BMMNC infusion after a median follow-up duration of 6 months. Conclusions-Intracoronary infusion of BMMNC is safe, but does not enhance cardiac function on MRI-derived parameters, nor does it improve clinical outcome. New and possibly more potent stem cells are emerging in the field, but their clinical efficacy still needs to be defined in future trials.
Stem cell therapy in acute myocardial infarction: A pot of gold or Pandora's box
2011
Stem cell therapy for conditions characterized by myocyte loss in myocardial infarction and heart failure is intuitively appealing. Stem cells from various sources, including heart itself in preclinical and animal studies, have shown the potential to improve the function of ventricular muscle after ischaemic injury. The clinical experience from worldwide studies have indicated the safety profile but with modest benefits. The predominant mechanisms of transplanted cells for improving cardiac function have pointed towards paracrine effects rather than transdifferentiation into cardiomyocytes. Thus, further investigations should be encouraged towards bench side and bedside to resolve various issues for ensuring the correct type and dosing of cells, time, and method of delivery and identify correct mechanism of functional improvement. An interdisciplinary effort at the scientific, clinical, and the government front will bring successful realization of this therapy for healing the heart and may convert what seems now a Pandora's Box into a Pot of Gold.
Interactive cardiovascular and thoracic surgery, 2011
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'Can intracoronary stem cell injection permanently improve cardiac function after myocardial infarction?'. Altogether 314 papers were found using the reported search, of which five represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that stem cells may have controversial effects on cardiac function in long-term follow-up of more than two years as they improved the left ventricular ejection fraction and end systolic volume index just in two studies in which none of them utilized cardiac magnetic resonance imaging (MRI), as the most reliable method, to quantify cardiac function. However, all remaining three trials which reported negative results used cardiac MRI for assessment of cardiac inde...