Myocardial infarction, commonly known as a heart attack, or ischemic heart disease (IHD), remains one of the most fatal health conditions worldwide due to the limited regenerative capacity of the heart muscle after infarction. Conventional medical treatments primarily focus on symptom control and tissue preservation but fail to address the loss of cardiomyocytes, the cells responsible for heart contraction. This systematic review explores the hypothesis that stem cell therapies can enhance cardiac regeneration by replacing or repairing damaged myocardium, with a focus on mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and embryonic stem cells (ESCs). The review was restricted to literature published between 2015 and 2024, sourced from PubMed, Web of Science, and Google Scholar. This timeframe reflects advances in stem cell research and regenerative therapies. Findings from trials such as Bone Marrow-Derived Mononuclear Cell Therapy in Acute Myocardial Infarction (BAMI) and Cardiopoietic Stem Cell Therapy in Heart Failure (C-CURE) suggest that stem cell therapies may improve left ventricular ejection fraction (LVEF) and reduce infarct size. However, the heterogeneity of trials, small sample sizes, and short follow-up durations limit the generalizability of these results. Long-term benefits, including improved survival rates and reduced hospital readmissions, remain inconclusive. Ethical concerns, particularly the use of ESCs, pose additional challenges, including controversies over embryonic sources and varying regulatory landscapes. Key areas for advancement include optimizing stem cell survival and differentiation, with genetic engineering to enhance tissue repair capabilities considered the most critical for improving clinical outcomes. The integration of regenerative treatments such as extracellular vesicle therapy, derived from stem cells to modulate repair, also shows promise. Imaging techniques, such as MRI and PET, provide real-time monitoring of stem cell effects, offering insights into therapeutic efficacy and safety. Despite promising results from preclinical models and early-phase trials, the full therapeutic potential of stem cell therapy for IHD remains unrealized. Effective treatment protocols, addressing patient-specific factors, ethical considerations, and long-term outcome evaluations, are essential. This review emphasizes the need for ongoing research and clinical development to maximize the potential of stem cell-based approaches in cardiac repair.

In this article, we evaluate the comparative efficacy and safety of mesenchymal stem cells (MSCs) derived from bone marrow (BM-MSCs) and umbilical cord (UC-MSCs) in the treatment of heart failure and myocardial infarction. MSCs have gained importance as living bio drug due to their regenerative potential, with BM-MSCs being the most extensively studied. However, UC-MSCs offer unique advantages, such as noninvasive collection and fewer ethical concerns. This systematic review and meta-analysis summarizes data from 13 randomized controlled trials, which included a total of 693 patients. Their study shows that UC-MSCs significantly improved left ventricular ejection fraction by 5.08% at 6 months and 2.78% at 12 months compared with controls, while BM-MSCs showed no significant effect. Neither cell type showed significant changes in 6-minute walk distance. In addition, UC-MSCs and BM-MSCs had comparable safety profiles, with no significant differences in major adverse cardiac events, except for a lower rehospitalization rate observed with BM-MSCs. These results position UC-MSCs as a promising alternative in MSC-based therapies for cardiac disease, offering potential improvements in cardiac function while maintaining a favorable safety profile. Future research should focus on optimizing administration protocols and further exploring the long-term benefits and mechanisms of UC-MSCs in cardiac repair.

Stem cell therapy is a promising approach for treating chronic diabetic wounds. However, its effectiveness is significantly limited by the high oxidative stress environment and persistent inflammation induced by diabetes. Strategies to overcome these challenges are essential to enhance the therapeutic potential of stem cell therapy.

Cu5.4O ultrasmall nanoparticles (Cu5.4O-USNPs), known for their excellent reactive oxygen species (ROS) scavenging properties, were utilized to protect adipose-derived stem cells (ADSCs) from oxidative stress injury. In vitro experiments were conducted to evaluate the viability, paracrine activity, and anti-inflammatory capabilities of ADSCs loaded with Cu5.4O-USNPs under oxidative stress conditions. In vivo experiments in diabetic mice were performed to assess the therapeutic effects of Cu5.4O-USNP-loaded ADSCs on wound healing, including their impact on inflammation, collagen synthesis, angiogenesis, and wound closure.

ADSCs treated with Cu5.4O-USNPs showed significantly enhanced viability, paracrine activity, and anti-inflammatory properties under oxidative stress conditions in vitro. In diabetic mice, Cu5.4O-USNP-loaded ADSCs reduced inflammatory responses in wound tissues, promoted collagen synthesis and angiogenesis, and accelerated diabetic wound healing. These findings suggest that Cu5.4O-USNPs effectively mitigate the adverse effects of oxidative stress and inflammation, enhancing the therapeutic efficacy of ADSCs.

This study presents a simple and effective approach to improve the therapeutic potential of stem cell therapy for diabetic wounds. By incorporating Cu5.4O-USNPs, the antioxidative and anti-inflammatory capabilities of ADSCs are significantly enhanced, offering a promising strategy for ROS-related tissue repair and chronic wound healing.

Mesenchymal stem cells (MSCs) have demonstrated significant therapeutic potential in heart failure (HF) treatment. However, their clinical application is impeded by low retention rate and low cellular activity of MSCs caused by high inflammatory and reactive oxygen species (ROS) microenvironment. In this study, monascus pigment (MP) nanoparticle (PPM) was proposed for improving adverse microenvironment and assisting in transplantation of bone marrow-derived MSCs (BMSCs). Meanwhile, in order to load PPM and reduce the mechanical damage of BMSCs, injectable hydrogels based on Schiff base cross-linking were prepared. The PPM displays ROS-scavenging and macrophage phenotype-regulating capabilities, significantly enhancing BMSCs survival and activity in HF microenvironment. This hydrogel demonstrates superior biocompatibility, injectability, and tissue adhesion. With the synergistic effects of injectable, adhesive hydrogel and the microenvironment-modulating properties of MP, cardiac function was effectively improved in the pericardial sac of rats. Our results offer insights into advancing BMSCs-based HF therapies and their clinical applications.

JOURNAL/nrgr/04.03/01300535-202409000-00035/figure1/v/2024-01-16T170235Z/r/image-tiff Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy, neurosensory impairments, and cognitive deficits, and there is no effective treatment for complications related to hypoxic-ischemic encephalopathy. The therapeutic potential of human placental chorionic plate-derived mesenchymal stem cells for various diseases has been explored. However, the potential use of human placental chorionic plate-derived mesenchymal stem cells for the treatment of neonatal hypoxic-ischemic encephalopathy has not yet been investigated. In this study, we injected human placental chorionic plate-derived mesenchymal stem cells into the lateral ventricle of a neonatal hypoxic-ischemic encephalopathy rat model and observed significant improvements in both cognitive and motor function. Protein chip analysis showed that interleukin-3 expression was significantly elevated in neonatal hypoxic-ischemic encephalopathy model rats. Following transplantation of human placental chorionic plate-derived mesenchymal stem cells, interleukin-3 expression was downregulated. To further investigate the role of interleukin-3 in neonatal hypoxic-ischemic encephalopathy, we established an in vitro SH-SY5Y cell model of hypoxic-ischemic injury through oxygen-glucose deprivation and silenced interleukin-3 expression using small interfering RNA. We found that the activity and proliferation of SH-SY5Y cells subjected to oxygen-glucose deprivation were further suppressed by interleukin-3 knockdown. Furthermore, interleukin-3 knockout exacerbated neuronal damage and cognitive and motor function impairment in rat models of hypoxic-ischemic encephalopathy. The findings suggest that transplantation of hpcMSCs ameliorated behavioral impairments in a rat model of hypoxic-ischemic encephalopathy, and this effect was mediated by interleukin-3-dependent neurological function.

Cardiovascular diseases (CVDs) are the leading cause of death and include several vascular and cardiac disorders, such as atherosclerosis, coronary artery disease, cardiomyopathies, and heart failure. Multiple treatment strategies exist for CVDs, but there is a need for regenerative treatment of damaged heart. Stem cells are a broad variety of cells with a great differentiation potential that have regenerative and immunomodulatory properties. Multiple studies have evaluated the efficacy of stem cells in CVDs, such as mesenchymal stem cells and induced pluripotent stem cell-derived cardiomyocytes. These studies have demonstrated that stem cells can improve the left ventricle ejection fraction, reduce fibrosis, and decrease infarct size. Other studies have investigated potential methods to improve the survival, engraftment, and functionality of stem cells in the treatment of CVDs. The aim of the present review is to summarize the current evidence on the role of stem cells in the treatment of CVDs, and how to improve their efficacy.