A critical challenge: Dosage-related efficacy and acute complication intracoronary injection of autologous bone marrow mesenchymal stem cells in acute myocardial infarction

Gao, Lei; Xue, Ping; Ding, Qingqing; Chen, Yu; Zhang, Ning K.; Chen, Hai Y.; Wang, Zhi G.; Wang, Yun F.; Zhu, Zhihao; Li, Tian C.; Liu, Hui L.; Tong, Zi C.; Yang, Yong; Nan, Xue; Guo, Feng; Shen, Jian; Shen, Yan; Zhang, Jian Jun; Fei, Yu X.; Xu, Hongtao; Wang, Li H.; Tian, Hao; Liu, Da Q.; Yang, Ye

doi:10.1016/j.ijcard.2013.04.112

Cited by 73 publications

(69 citation statements)

References 30 publications

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“…Of the 23 included studies, 11 evaluated AMI ( n = 509 patients) and 12 evaluated IHF ( n = 639 patients) (Table ). Of these studies, eight were RCTs that evaluated AMI ( n = 429 patients) and five were RCTs that evaluated IHF ( n = 472 patients) . The number of evaluated patients who received MSCs ranged from 9 to 58 patients for the AMI studies and from 6 to 107 patients for the IHF studies.…”

Section: Resultsmentioning

confidence: 99%

Safety and Efficacy of Adult Stem Cell Therapy for Acute Myocardial Infarction and Ischemic Heart Failure (SafeCell Heart): A Systematic Review and Meta-Analysis

Lalu

Mazzarello

Zlepnig

et al. 2018

Stem Cells Translational Medicine

103

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Preclinical and clinical evidence suggests that mesenchymal stem cells (MSCs) may be beneficial in treating both acute myocardial infarction (AMI) and ischemic heart failure (IHF). However, the safety profile and efficacy of MSC therapy is not well‐known. We conducted a systematic review of clinical trials that evaluated the safety or efficacy of MSCs for AMI or IHF. Embase, PubMed/Medline, and Cochrane Central Register of Controlled Trials were searched from inception to September 27, 2017. Studies that examined the use of MSCs administered to adults with AMI or IHF were eligible. The Cochrane risk of bias tool was used to assess bias of included studies. The primary outcome was safety assessed by adverse events and the secondary outcome was efficacy which was assessed by mortality and left ventricular ejection fraction (LVEF). A total of 668 citations were reviewed and 23 studies met eligibility criteria. Of these, 11 studies evaluated AMI and 12 studies evaluated IHF. There was no association between MSCs and acute adverse events. There was a significant improvement in overall LVEF in patients who received MSCs (SMD 0.73, 95% CI 0.24–1.21). No significant difference in mortality was noted (Peto OR 0.68, 95% CI 0.38–1.22). Results from our systematic review suggest that MSC therapy for ischemic heart disease appears to be safe. There is a need for a well‐designed adequately powered randomized control trial (with rigorous adverse event reporting and evaluations of cardiac function) to further establish a clear risk‐benefit profile of MSCs. Stem Cells Translational Medicine 2018;7:857–866

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Section: Resultsmentioning

confidence: 99%

Safety and Efficacy of Adult Stem Cell Therapy for Acute Myocardial Infarction and Ischemic Heart Failure (SafeCell Heart): A Systematic Review and Meta-Analysis

Lalu

Mazzarello

Zlepnig

et al. 2018

Stem Cells Translational Medicine

103

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“…After 6 months, they found a reduction in LV infarction percentage (15.3% ± 2.6% vs. 31.6% ± 5.3%) by cardiac MRI in the cell‐treated group, in addition to an improvement in the MIBI‐SPECT perfusion defect. In contrast, Gao et al injected 3.0 × 10 6 MSCs 14 days postacute MI, and found no significant difference in LVEF between MSC‐treated and placebo‐treated groups up to 24 months post injection .…”

Section: Clinical Trials Of Mscs For Ischemic Heart Diseasementioning

confidence: 94%

Concise Review: Rational Use of Mesenchymal Stem Cells in the Treatment of Ischemic Heart Disease

Ward

Abadeh

Connelly

2018

Stem Cells Translational Medicine

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The capacity of stem and progenitor cells to stimulate cardiac regeneration has been studied for almost 20 years, with very promising preclinical data and mixed clinical results. Several cell types have been studied, identified by their cell surface markers, differentiation capacity and their secreted growth factors. Bone marrow derived mesenchymal stem cells (MSCs) have been found to have potent regenerative capacity, through multiple mechanisms, including mesoderm lineage differentiation, immunomodulation, and paracrine stimulation. MSCs also secrete exosomes and microvesicles, which themselves contain potent angiogenic cytokines or mRNA molecules with effects on their local milieu. This concise review summarizes the mechanisms of MSC‐based cardiac regeneration and highlighting results from molecular and preclinical studies. We also discuss clinical trial results to date, and ongoing studies. Furthermore, we discuss novel approaches for the enhancement of MSC based cardiac regeneration, such as genetic modification. stem cells translational medicine 2018;7:543–550

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“…In addition, the risk of vascular embolisms must be considered [49]. In an ischemic rat model subjected to intracavitary SPION-labeled MSC injection, high SMF intensities induced cell accumulation in the vessel lumen [49, 50]. In this study, a permanent magnet was placed next to the injured myocardium for only 20 min (10 min after and 10 min before cell injection).…”

Section: Concernsmentioning

confidence: 99%

Magnetic targeting as a strategy to enhance therapeutic effects of mesenchymal stromal cells

et al. 2017

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Mesenchymal stromal cells (MSCs) have been extensively investigated in the field of regenerative medicine. It is known that the success of MSC-based therapies depends primarily on effective cell delivery to the target site where they will secrete vesicles and soluble factors with immunomodulatory and potentially reparative properties. However, some lesions are located in sites that are difficult to access, such as the heart, spinal cord, and joints. Additionally, low MSC retention at target sites makes cell therapy short-lasting and, therefore, less effective. In this context, the magnetic targeting technique has emerged as a new strategy to aid delivery, increase retention, and enhance the effects of MSCs. This approach uses magnetic nanoparticles to magnetize MSCs and static magnetic fields to guide them in vivo, thus promoting more focused, effective, and lasting retention of MSCs at the target site. In the present review, we discuss the magnetic targeting technique, its principles, and the materials most commonly used; we also discuss its potential for MSC enhancement, and safety concerns that should be addressed before it can be applied in clinical practice.

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A critical challenge: Dosage-related efficacy and acute complication intracoronary injection of autologous bone marrow mesenchymal stem cells in acute myocardial infarction

Cited by 73 publications

References 30 publications

Safety and Efficacy of Adult Stem Cell Therapy for Acute Myocardial Infarction and Ischemic Heart Failure (SafeCell Heart): A Systematic Review and Meta-Analysis

Safety and Efficacy of Adult Stem Cell Therapy for Acute Myocardial Infarction and Ischemic Heart Failure (SafeCell Heart): A Systematic Review and Meta-Analysis

Concise Review: Rational Use of Mesenchymal Stem Cells in the Treatment of Ischemic Heart Disease

Magnetic targeting as a strategy to enhance therapeutic effects of mesenchymal stromal cells

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