Terapia celular

Clin Transl Med. 2025 Sep;15(9):e70475. doi: 10.1002/ctm2.70475.

ABSTRACT

BACKGROUND: To investigate the role of self-peripheral blood mesenchymal stem cell (PBMSC)-derived exosomes (Exos) in enhancing renal sympathetic denervation (RD)-mediated heart regeneration following myocardial infarction (MI) in a porcine model.

METHODS: Pigs (ejection fraction [EF] < 40% post-MI) were randomised to early sham RD or RD. At 2 weeks post-MI, autologous PBMSC-Exos were collected. At 30 days post-MI, pigs received either PBMSC-Exos (2 × 1013 particles) or phosphate-buffered saline and were followed until 90 days. Another cohort underwent myocardial biopsy at 14 days post-MI to assess PBMSC-Exos effects on ischaemic cardiomyocyte (CM) reprogramming, followed by adeno-associated viral therapy with miR-141-200-429 sponges or negative control sponges to explore the role of miR-141-200-429 clusters in reprogramming.

RESULTS: Two weeks post-MI, RD hearts showed increased Exos uptake and inhibited the sympathetic nervous system. By 90 days, the RD+Exos group had 11%-26% higher EF than single-treatment groups (all p < .001), with improved survival and reduced fibrosis. Exos therapy enhanced RD effects by suppressing the renin‒angiotensin‒aldosterone system and transferring the miR-141-200-429 cluster into ischaemic CMs. CMs from RD-treated hearts cocultured with PBMSC-ExosRD exhibited a more immature state, promoting reprogramming. β-Catenin overexpression further enhanced PBMSC-ExosRD effects, while miR-141-200-429 inhibition blocked RD-induced CM reprogramming and survival. Ultimately, PBMSC-ExosRD reduced dickkopf-1 (Dkk1) expression and activated GSK3β phosphorylation, thereby stimulating the Wnt/β-catenin pathway.

CONCLUSIONS: PBMSC-ExosRD enhances RD-mediated cardiac repair through miR-141-200-429 cluster-dependent activation of the Wnt/β-catenin pathway, offering a novel therapeutic strategy for MI-induced heart failure. Our findings unveil a novel therapeutic strategy, highlighting that RD maintains its efficacy and safety when integrated with complementary approaches over extended periods.

KEY POINTS: Myocardial infarction triggers cardiomyocyte depletion and sympathetic overactivation, culminating in irreversible heart failure. Renal denervation (RD) attenuates sympathetic signalling, modulating catecholamine‒B-type natriuretic peptide (BNP) homeostasis. We newly demonstrate RD-enhanced peripheral blood mesenchymal stem cell exosomal secretion enriched with miR-141-200-429 clusters. These exosomal miRNAs suppress dickkopf-1 (Dkk1), activating GSK3β/Wnt/β-catenin signalling to enhance myocardial survival and regeneration. Our findings establish a combined therapeutic paradigm wherein RD maintains durable efficacy and safety alongside complementary interventions for heart failure management.

PMID:40910352 | PMC:PMC12411928 | DOI:10.1002/ctm2.70475

RSC Adv. 2025 Sep 2;15(38):31564-31585. doi: 10.1039/d5ra05286f. eCollection 2025 Aug 29.

ABSTRACT

Myocardial infarction (MI) is one of the leading causes of heart failure and death worldwide. While conventional treatments have limitations in promoting myocardial repair and regeneration, hydrogel, as a multifunctional biomaterial, shows great potential in MI treatment due to its unique physicochemical properties and biocompatibility. This paper reviews the multifunctional applications of hydrogels in MI therapeutics, including drug delivery (miRNAs, exosomes, etc.), electrical conduction, immunomodulation, detection, tissue engineering, and microfluidic functions. In terms of drug delivery, hydrogels are able to precisely deliver drugs, stem cells and exosomes to improve the microenvironment of the infarcted area through their controlled release properties. In the field of electrical conduction, hydrogels are used as scaffolding materials that mimic the mechanical and electrical properties of myocardial tissues. The role of hydrogels in immunomodulation has also attracted much attention. In addition, the application of hydrogels in biosensing and detection functions provides new strategies for real-time monitoring of MI. In summary, hydrogels have demonstrated multifunctional advantages in MI therapy, but their clinical applications still face challenges, such as the long-term biocompatibility of the materials and the feasibility of large-scale production. Future research should focus on optimizing the design of hydrogels for more precise treatment and wider applications.

PMID:40904844 | PMC:PMC12403691 | DOI:10.1039/d5ra05286f

Front Cardiovasc Med. 2025 Aug 19;12:1634877. doi: 10.3389/fcvm.2025.1634877. eCollection 2025.

ABSTRACT

Ischemia-reperfusion injury, marked by transient blood flow disruption followed by tissue reperfusion, constitutes a unifying pathological mechanism across cerebral stroke, myocardial infarction, and acute kidney injury. Hypoxia, a central driver of ischemia-reperfusion injury progression, triggers molecular cascades that simultaneously exacerbate tissue damage and activate compensatory repair mechanisms. Notably, hypoxia-induced angiogenesis and vascular remodeling serve as critical adaptive processes for functional recovery, supporting neuronal plasticity in stroke, myocardial salvage in infarction, and tubular regeneration in renal ischemia-reperfusion injury. While these conditions exhibit organ-specific manifestations, emerging studies underscore conserved regulatory frameworks mediated by extracellular vesicles (EVs) and their molecular cargoes, which orchestrate cross-organ protective responses. In this context, mesenchymal stem cell (MSC)-derived EVs have emerged as potent therapeutic agents for mitigating ischemia-reperfusion injury-related deficits, as evidenced by preclinical and clinical studies. These EVs act as bioactive nanocarriers, delivering cargos that modulate shared pathological pathways-particularly angiogenesis, a linchpin of post-ischemic tissue repair. Accumulating evidence highlights cargos within MSC-EVs (e.g., miRNAs, proteins) as master regulators of vascular regeneration, fine-tuning endothelial proliferation, vessel maturation, and hypoxia adaptation. This review systematically examines the dual roles of MSC-EV-associated cargos in promoting or suppressing angiogenesis across cerebral, cardiac, and renal ischemia-reperfusion injury models. By dissecting their mechanisms in spatiotemporal regulation of vascular signaling networks, we aim to elucidate their translational potential as universal therapeutic targets for multi-organ ischemia-reperfusion injury management.

PMID:40904530 | PMC:PMC12403218 | DOI:10.3389/fcvm.2025.1634877

Stem Cell Res Ther. 2025 Sep 2;16(1):485. doi: 10.1186/s13287-025-04357-8.

ABSTRACT

BACKGROUND: Myocardial infarction (MI) results in loss of cardiomyocytes leading to heart failure. Despite advancements in pharmacotherapy and interventions such as revascularization, ischemic heart failure remains a challenge. Recent advancements in stem cell therapies, genetic engineering and bioengineering have shown to improve cardiac function and quality of life.

METHODOLOGY: Following PRISMA guidelines, randomized controlled trials clinical trials from last 12 years were systematically reviewed. All the patients included in these studies had ischemic heart failure and were subjected to different types of stem cell therapies. Protocol for this meta-analysis is registered on PROSPERO (Registration no: CRD42023399263). Data extraction and Quality assessment was done according to Cochrane handbook of systematic reviews and meta-analysis. Meta-analysis was conducted using Revman, and a random-effect model was used to calculate weighted mean differences (WMD) in left ventricular ejection fraction (LVEF), scar size and Minnesota Living with Heart Failure score (MLHFQ) pre- and post-intervention.

RESULTS: The pooled mean difference (MD) for scar size reduction at 6 months follow-up was - 0.36; (95%CI [-0.63, -0.10]), I2 = 71% (p < 0.0001) and at 12 months follow-up was - 0.62; (95%CI [-1.03, -0.21]), I2 = 78% (p < 0.0001) with a positive effect direction. Weight of the studies ranged from 5.4 to 10.8% and 9.6-14.1% at 6 months and 12 months follow-up respectively. The pooled data analysis at 6 months and 12 months follow-up revealed weighted mean difference 0.44; (95% CI [0.13-0.75]), I2 = 85% (p < 0.00001) and 0.64; 95% CI [0.14-1.14], I2 = 85% (p < 0.00001) respectively. For MHLFQ score pooled weighted mean difference was calculated for 286 patients which revealed mean difference - 0.38, (95% CI [-0.71-0.05]) (p = 0.02), I2 = 69% (p < 0.002). Sensitivity analysis by excluding 'Gujjaro et al. 2016' revealed weighted mean difference - 0.49; (95% CI [-0.74-0.25]) (p < 0.0001), I2 = 72% (p = 0.09).

CONCLUSIONS: Our meta-analysis not only demonstrated consistent improvements in LVEF and reductions in scar size but also improvement in quality of life with stem cell therapies, however, the heterogeneity among studies calls for a need of standardized protocols and further research in optimizing these therapies to improve cardiomyocyte regeneration and overall cardiac repair.

PMID:40898343 | PMC:PMC12403498 | DOI:10.1186/s13287-025-04357-8

Acta Biomater. 2025 Aug 30:S1742-7061(25)00649-X. doi: 10.1016/j.actbio.2025.08.057. Online ahead of print.

ABSTRACT

Background Myocardial infarction leads to irreversible cardiomyocyte loss and adverse ventricular remodeling, often culminating in heart failure. Transplantation of functional cardiac patches offers a promising avenue for myocardial repair, yet current delivery methods typically require open-chest surgery and suturing of the graft, limiting their applicability in patients with severe heart failure. Methods We developed an engineered heart tissue composed of human induced pluripotent stem cell-derived cardiomyocytes, endothelial cells, and fibroblasts seeded on a durable, flexible scaffold. The scaffold was made of intertwined poly lactide-co-glycolide nano- and microfiber hybrid aerogels coated with gelatin of shape-recoverable property, ensuring mechanical resilience and flexibility for thoracoscopic delivery. Engineered heart tissues were loaded with pro-angiogenic factors including fibroblast growth factor 1 and CHIR99021. After in vitro characterization and optimization, engineered heart tissues were delivered to rats via thoracoscopy at 28 days after myocardial infarction induction. Echocardiography and histological analysis were used to assess cardiac function and heart remodeling. Results Engineered heart tissues exhibited structural integrity under mechanical compression. Thoracoscopy-based epicardial engineered heart tissue transplantation to rats with chronic myocardial infarction significantly improved left ventricular ejection fraction and fractional shortening, concomitant with reduced fibrosis, cardiomyocyte apoptosis, and inflammation, as well as enhanced vascularization. Furthermore, engineered heart tissues modulated the immune response by decreasing neutrophil and macrophage infiltration. Conclusions These findings establish the feasibility of a minimally invasive approach for delivery of engineered heart tissues, eliminating the need for suturing and offering a less invasive alternative to transplantation, thereby broadening the clinical potential of engineered heart tissue-based therapy for heart failure. STATEMENT OF SIGNIFICANCE: Transplantation of engineered heart tissues emerges as a promising approach for regenerating myocardium and improving cardiac function in preclinical models of heart failure. However, clinical translation remains challenged due to the invasive nature of current delivery methods, which often involve open-chest procedures that pose significant risks, particularly for patients with severe heart failure. This study introduces an engineered heart tissue (EHT) made from human induced pluripotent stem cells-derived cardiac cells on a flexible scaffold, and shows that EHTs can be delivered to animal models of chronic myocardial infarction using a minimally invasive, video-assisted thoracoscopic approach. This approach offers a safer alternative to open-chest surgery for EHT treatment of patients with end-stage heart failure.

PMID:40889668 | PMC:PMC12450543 | DOI:10.1016/j.actbio.2025.08.057

Nucleosides Nucleotides Nucleic Acids. 2025 Sep 1:1-29. doi: 10.1080/15257770.2025.2550969. Online ahead of print.

ABSTRACT

Heart failure (HF) is not a disease but a combination of signs and symptoms caused by the failure of the heart to pump blood to support the circulatory system at rest or during activity. HF is the potential end stage of all heart diseases in which cardiomyopathies are a diverse group of cardiac disorders with distinct phenotypes, depending on the protein and pathways affected. Cardiomyopathies represent major causes of morbidity and mortality at all ages in humans in which hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), are the most common. Among the different common diagnostic tests for heart failure such as physical examination, blood tests, chest X-rays, electrocardiogram (ECG), etc. ultrasound has also been used not only for diagnosis such as echocardiography but also for therapeutic purposes. The development of therapeutic strategies for HF aiming to improve the heart's function, delay progression of HF, and treat HF symptoms as well as to stimulate the capacity to regenerate cardiomyocytes via stem cell therapy have been under intensive research interest. This narrative review aims to present the current understanding of the pathogenesis, diagnosis, and treatment of HF. Furthermore, as a perspective, this review navigates emerging therapies for HF by emphasizing on the use of low-intensity pulsed ultrasound (LIPUS) as a noninvasive therapy for (1) stimulation of the myocardial tissue reconstruction mechanisms; and (2) exploration of the molecular mechanisms behind the mechanotransduction from the muscle LIM protein (MLP), which is believed to be involved in human HF, using its expression vector via glycosylphosphatidylinositol, GPI, anchor.

PMID:40889110 | DOI:10.1080/15257770.2025.2550969

Int J Mol Sci. 2025 Aug 21;26(16):8100. doi: 10.3390/ijms26168100.

ABSTRACT

Renocardiac syndrome type 4 (RCS4) is a common comorbid pathology, but the mechanisms of kidney dysfunction-induced cardiac remodeling and the involvement of cardiac progenitor cells (CPCs) in this process remain unclear. The aim of this study was to investigate the structural and functional changes in the cardiac muscle in RCS4 induced by unilateral ureteral obstruction (UUO) and the role of nestin+ CPCs in these. Heart function and localization of nestin+ cells in the myocardium were assessed using nestin-GFP transgenic mice subjected to UUO for 14 and 28 days. UUO resulted in cardiac hypertrophy, accompanied by an elongation of the QRS wave on the ECG, decreased expression of Cxcl1, Cxcl9, and Il1b, reduced the number of CD11b+ cells, and increased in titin isoform parameters, such as T1/MHC and TT/MHC ratios, without changes in fibrosis markers. The number of nestin+ cells increased in the myocardium with increased duration of UUO and displayed an SCA-1+TBX5+ phenotype, consistent with CPCs. Thus, cardiac pathology in RCS4 was manifested by cardiomyocyte hypertrophy with changes in the electrophysiological phenotype of the heart, not accompanied by fibrosis or inflammation. Nestin+ cardiac cells retained the CPC phenotype during UUO, and their number increased, which suggests their participation in regenerative processes in the heart.

PMID:40869420 | PMC:PMC12386493 | DOI:10.3390/ijms26168100

Biol Cell. 2025 Aug;117(8):e70028. doi: 10.1111/boc.70028.

ABSTRACT

Cardiac regeneration is hindered by the permanent cell cycle arrest of cardiomyocytes post-birth, leading to compensatory fibrosis and impaired cardiac function after injury. While the role of cell cycle regulatory proteins is well understood, the impact of long non-coding RNAs (lncRNAs) remains unclear. To address this gap, we reanalyzed public transcriptomic datasets comparing pre- and post-natal ventricular cardiomyocytes. In silico analysis identified differentially expressed lncRNAs, with four candidates selected for further validation. Human embryonic stem cells (hESCs) were differentiated into cardiomyocytes, and their cell cycle status was assessed on Days 10, 20, and 30. The expression of in silico-identified lncRNAs was evaluated in proliferative (Day 10) and non-proliferative (Days 20 and 30) hESC-derived cardiomyocytes, resembling pre- and post-natal ventricular cardiomyocytes. Among the candidates, STARD4-AS1 and H19 showed a permanent downregulation pattern in both in silico and in vitro assays. STARD4-AS1 and H19 lncRNAs might reside in the regulatory network of cardiomyocytes cell cycle arrest and as targets for cardiac regenerative strategies.

PMID:40851346 | DOI:10.1111/boc.70028

Medicine (Baltimore). 2025 Aug 15;104(33):e43878. doi: 10.1097/MD.0000000000043878.

ABSTRACT

The phenotype of stem cell-derived cardiomyocytes is far from that of adult cardiomyocytes. Specifically, it is characterized by spontaneous contraction, irregular morphology, and differences in sarcomere components and metabolism. Human cardiomyocyte maturation involves a shift in metabolism from glycolysis to fatty acid oxidation. This metabolic shift alters gene expression and inhibits proliferation. These findings indicate that the glucose concentration manipulates cardiomyocyte metabolism and modulates maturation. This review summarizes the main phenotypic differences, focusing on changes in myocardial cell metabolism. We also summarize the effect of the glucose concentration on maturity of stem cell-derived cardiomyocytes, and how glucose may support a novel maturation strategy.

PMID:40826763 | PMC:PMC12366996 | DOI:10.1097/MD.0000000000043878

Polymers (Basel). 2025 Jul 30;17(15):2088. doi: 10.3390/polym17152088.

ABSTRACT

Myocardial infarction (MI) remains one of the most common cardiovascular diseases and a leading cause of morbidity and mortality worldwide. In recent years, natural polymeric patches have attracted increasing attention as a promising therapeutic platform for myocardial tissue repair. This study explored the fabrication and evaluation of screen-printed electrodes (SPEs) on chitosan film as a novel platform for cardiac patch applications. Chitosan is a biodegradable and biocompatible natural polymer that provides an ideal substrate for SPEs, providing mechanical stability and promoting cell adhesion. Silver ink was employed to enhance electrochemical performance, and the electrodes exhibited strong adhesion and structural integrity under wet conditions. Mechanical testing and swelling ratio analysis were conducted to assess the patch's physical robustness and aqueous stability. Silver ink was employed to enhance electrochemical performance, which was evaluated using cyclic voltammetry. In vitro, electrical stimulation through the chitosan-SPE patch significantly increased the expression of cardiac-specific genes (GATA-4, β-MHC, troponin I) in bone marrow mesenchymal stem cells (BMSCs), indicating early cardiogenic differentiation potential. In vivo, the implantation of the chitosan-SPE patch in a rat MI model demonstrated good tissue integration, preserved myocardial structure, and enhanced ventricular wall thickness, indicating that the patch has the potential to serve as a functional cardiac scaffold. These findings support the feasibility of screen-printed electrodes fabricated on chitosan film substrates as a cost-effective and scalable platform for cardiac repair, offering a foundation for future applications in cardiac tissue engineering.

PMID:40808135 | PMC:PMC12349067 | DOI:10.3390/polym17152088

Cells. 2025 Aug 1;14(15):1188. doi: 10.3390/cells14151188.

ABSTRACT

Diabetes mellitus, both type 1 (T1D) and type 2 (T2D), has become the epidemic of the century and a major public health concern given its rising prevalence and the increasing adoption of a sedentary lifestyle globally. This multifaceted disease is characterized by impaired pancreatic beta cell function and insulin resistance (IR) in peripheral organs, namely the liver, skeletal muscle, and adipose tissue. Additional insulin target tissues, including cardiomyocytes and neuronal cells, are also affected. The advent of stem cell research has opened new avenues for tackling this disease, particularly through the regeneration of insulin target cells and the establishment of disease models for further investigation. Human-induced pluripotent stem cells (iPSCs) have emerged as a valuable resource for generating specialized cell types, such as hepatocytes, myocytes, adipocytes, cardiomyocytes, and neuronal cells, with diverse applications ranging from drug screening to disease modeling and, importantly, treating IR in T2D. This review aims to elucidate the significant applications of iPSC-derived insulin target cells in studying the pathogenesis of insulin resistance and T2D. Furthermore, recent differentiation strategies, protocols, signaling pathways, growth factors, and advancements in this field of therapeutic research for each specific iPSC-derived cell type are discussed.

PMID:40801620 | PMC:PMC12345660 | DOI:10.3390/cells14151188

Tissue Eng Part B Rev. 2025 Aug 7. doi: 10.1177/19373341251364282. Online ahead of print.

ABSTRACT

Myocardial infarction (MI), a prevalent critical cardiovascular disease (CVD), poses a severe threat to patients' lives. Despite the availability of pharmacological, interventional, and surgical treatments in clinical practice, these conventional therapies encounter the bottleneck of difficulty in repairing and reconstructing damaged myocardial tissue. Additionally, novel cardiac repair approaches based on stem cell and cardiomyocyte injections are restricted by the harsh microenvironment of infarcted areas. However, biomaterial hydrogels emerge as promising candidates for MI treatment due to their strong mechanical properties, good biocompatibility, high water absorption capacity, and excellent anti-inflammatory and antioxidant properties. These features enable them to enhance the microenvironment, promote myocardial regeneration, and restore myocardial function. This article delves into the therapeutic effects of sodium alginate (SA) and its composite hydrogel materials in repairing and regenerating myocardial injuries caused by MI. Furthermore, it offers insights into the future research directions of SA and its composite hydrogel materials. It also explores their potential applications in the field of CVDs. Impact Statement This review article highlights the significance and potential impact of sodium alginate (SA)-based hydrogels in myocardial infarction (MI) treatment. It effectively communicates the importance of the research, the gap in the current treatments for MI, and how the reviewed SA hydrogels offer a promising solution with their unique properties. It also clearly states the intended contribution to the field and the potential benefits for researchers and clinicians.

PMID:40772844 | DOI:10.1177/19373341251364282

Circ Res. 2025 Aug 29;137(6):846-859. doi: 10.1161/CIRCRESAHA.125.326716. Epub 2025 Aug 5.

ABSTRACT

BACKGROUND: Myocardial ischemia-reperfusion (I/R) injury induces myocardial fibrosis that compromises cardiac function and electrical conduction, yet current clinical options remain inadequate. To address this unmet need, we explored macrophage-targeted lipid nanoparticles (LNPs) encapsulating FAP CAR (FAP [fibroblast activation protein]-targeted chimeric antigen receptor) mRNA for in vivo generation of FAP CAR macrophages and evaluated their therapeutic potential in reducing myocardial fibrosis and improving cardiac function after myocardial I/R injury.

METHODS: We formulated 1,2-dioleoyl-sn-glycero-3-phospho-l-serine-doping ALC-0315 (an ionizable lipid) LNP to deliver FAP CAR mRNA to generate FAP CAR macrophages. The platform was first validated in vitro by assessing phagocytosis of FAP-overexpressing fibroblasts by these macrophages. For in vivo evaluation, C57BL/6J mice subjected to I/R injury received intravenous administration of PBS, control LNPs, or LNP-FAP CAR (LNPs encapsulating mRNA encoding a FAP-targeting CAR). Comprehensive analyses included tracking the biodistribution of the resultant FAP CAR macrophages, quantitative measurement of fibrosis reduction, assessment of cardiac function by echocardiography, and safety evaluations.

RESULTS: LNP-FAP CAR successfully generated functional FAP CAR macrophages that demonstrated phagocytosis ability toward FAP-positive fibroblasts in vitro. In vivo studies revealed that intravenous delivery of LNP-FAP CAR generated functional FAP CAR macrophages that selectively engaged and phagocytosed activated cardiac fibroblasts in I/R mouse hearts. This targeted cell clearance translated to a significant reduction in the number of activated cardiac fibroblasts and the extent of myocardial fibrosis, as well as marked improvement in cardiac function without detectable toxicities. Notably, these effects were achievable even when intervention was delayed for up to 2 weeks post-I/R.

CONCLUSIONS: Our study demonstrates that FAP CAR macrophages generated in vivo by LNP-FAP CAR treatment effectively mitigate cardiac fibrosis and improve heart function after I/R injury, with lasting benefits and no observed toxicity. This safe and adaptable platform offers a promising treatment strategy for myocardial I/R injury and holds potential for treating other fibrotic heart diseases.

PMID:40762067 | DOI:10.1161/CIRCRESAHA.125.326716

Curr Cardiol Rev. 2025 Aug 1. doi: 10.2174/011573403X376065250728094646. Online ahead of print.

ABSTRACT

Cardiovascular diseases, especially myocardial infarction, remain the prominent causes of death globally, necessitating the exploration of innovative therapeutic strategies. Medical and surgical available treatments mainly manage disease symptoms and prevent deterioration, but do not focus on the repair of lost cardiomyocytes. Mesenchymal stem cells (MSCs) have emerged as a promising tool for heart repair and regeneration after injury, as they possess unique properties, such as the potential for differentiation into cardiomyocytes and vascular endothelial cells, immunomodulation, the release of mediators, and paracrine effects. This review focuses on the latest understanding of MSC therapies for cardiac repair, specifically addressing their properties, mechanism of action, preclinical and clinical studies, problems and prospects, and future strategies. MSCs can be isolated from various tissues, including bone marrow and adipose tissue, each with its own advantages and disadvantages in cardiac repair. Many preclinical studies conducted concluded that MSCs could differentiate into cardiomyocytes. MSCs involve multiple factors that enhance angiogenesis, promote the survival of existing myocardium and cardiomyocytes, reduce fibrosis, modulate the immune response, activate existing cardiac stem cells, and facilitate tissue remodeling; all of these processes are crucial in myocardial repair after MI. Although preclinical studies have promising outcomes, the application of MSC therapy in clinical trials has faced many challenges. Clinical trials conducted so far have yielded variable outcomes, with some showing marked improvements and others producing no promising results, indicating less improvement in cardiac function and mortality. This variability may be due to multiple sources, including MSCs, delivery methods, culture conditions, the timing of administration after MI, and patient-dependent factors, such as disease severity, overall patient well-being, and other comorbid conditions. The review concluded that although MSCs have a significant role in cardiac repair, further research is essential for overcoming current challenges to unlocking the maximum regenerative potential of these cells.

PMID:40760749 | DOI:10.2174/011573403X376065250728094646

J Stem Cells Regen Med. 2025 Jan 28;21(1):3-10. doi: 10.46582/jsrm.2101002. eCollection 2025.

ABSTRACT

The proposed topic is important because it helps find a lot of problems that happen when cardiovascular diseases are passed on along with fibrosis and the link between stem cells and myocardial regeneration. This study aims to investigate the effectiveness of autologous stem cells in the treatment of post-infarction myocardial changes. Statistical, bibliographic, and bibliosemantic research methods and scientific literature for the last 6 years were used to achieve the purpose. Cardiovascular diseases hold the highest prevalence and mortality rates, second only to the number of accidents. Today, there are many methods in the fight against coronary heart disease. However, drug therapy is the least effective, and instrumental methods are too invasive and entail several complications and side effects. Therefore, conducting detailed research on the impact of stem cells on the myocardium affected by infarction presents a challenge. Stem cell transplantation, which includes autologous bone marrow stem cells, typically leads to noticeable and significant changes in cardiac hemodynamic parameters and rheological properties. The development of autologous bone marrow stem cells during the angiogenesis process substantiates such metamorphoses. In addition, factors such as vascular endothelial growth factor and the whole list of coagulogram indicators may influence these changes. The practical significance of the raised subject is using stem cell therapy as an alternative, less invasive method in the fight against postinfarction myocardial changes.

PMID:40756129 | PMC:PMC12311326 | DOI:10.46582/jsrm.2101002

J Stem Cells Regen Med. 2025 May 29;21(1):1-2. doi: 10.46582/jsrm.2101001. eCollection 2025.

NO ABSTRACT

PMID:40756126 | PMC:PMC12311325 | DOI:10.46582/jsrm.2101001

Front Cell Dev Biol. 2025 Jul 17;13:1612589. doi: 10.3389/fcell.2025.1612589. eCollection 2025.

ABSTRACT

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are revolutionizing the field of regenerative medicine, becoming the core carriers of next-generation acellular therapeutic strategies. In contrast to traditional mesenchymal stem cell therapy, these nanoscale "regenerative tiny giants" offer significant advantages, including low immunogenicity, efficient biological barrier penetration, and stable storage. As natural bioactive molecular carriers, MSC-EVs precisely regulate the inflammatory response, angiogenesis, and tissue repair processes in target tissues by delivering functional RNA, proteins, and other signaling elements. They have demonstrated multidimensional therapeutic potential in diseases such as bone and joint regeneration, nerve function reconstruction, myocardial repair, and skin wound healing. Worldwide, 64 registered clinical trials have preliminarily validated the safety and applicability of MSC-EVs across various diseases. Notably, they have shown significant progress in treating severe coronavirus disease 2019 (COVID-19), ischemic stroke, and complex wound healing. However, the lack of standardization in production processes, insufficient targeting for in vivo delivery, and the scarcity of long-term biodistribution data remain core bottlenecks limiting the clinical translation of MSC-EVs. Future interdisciplinary technologies, including 3-dimensional (3D) dynamic culture, genetic engineering, and intelligent slow-release systems, are expected to facilitate the transition of MSC-EVs from the lab to large-scale applications. This shift may transform "injectable regenerative factors" into "programmable nanomedicines", offering new solutions for precision medicine.

PMID:40746857 | PMC:PMC12310703 | DOI:10.3389/fcell.2025.1612589

J Cell Physiol. 2025 Jul;240(7):e70076. doi: 10.1002/jcp.70076.

ABSTRACT

X.-H. Gong, H. Liu, S.-J. Wang, S.-W. Liang, and G.-G. Wang, "Exosomes Derived From SDF1-Overexpressing Mesenchymal Stem Cells Inhibit Ischemic Myocardial Cell Apoptosis and Promote Cardiac Endothelial Microvascular Regeneration in Mice With Myocardial Infarction." Journal of Cellular Physiology 234, no. 8 (2019): 13878-13893. https://doi.org/10.1002/jcp.28070. The above article, published online on February 5, 2019, in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor-in-Chief, Robert Heath, and Wiley Periodicals LLC. A third party shared a report from the National Natural Science Foundation of China, which indicated that data in this article had been purchased from an external company (National Natural Science Foundation of China 2015). An investigation by the publisher found that this fact is not reported in the article and also that the article is missing necessary information on the ethical approval for animal and human experiments performed as part of this study. The authors responded to an inquiry by the publisher requesting original data and evidence of approval for animal and human experiments. The authors stated that they conducted partial pre-experiments and then commissioned third-party companies to conduct the main experiments. The authors further stated that those companies could not provide raw data. The authors did not provide information regarding ethical approval for the animal and human experiments reported in the article. The authors requested the withdrawal of their article. The retraction has been agreed to because the data and ethical approval of experiments reported in this article cannot be validated.

PMID:40726436 | DOI:10.1002/jcp.70076

Stem Cell Res. 2025 Sep;87:103776. doi: 10.1016/j.scr.2025.103776. Epub 2025 Jul 16.

ABSTRACT

Understanding cell division in disease contexts is of paramount importance for elucidating disease mechanisms and developing regenerative therapies, such as cardiac regeneration. Nevertheless, tools for identifying and to studying key factors in regenerative processes in human cells remain scarce. Here, we generated a human induced pluripotent stem cell (hiPSC) reporter line expressing a cell cycle-regulated cyclinB1-eGFP construct that enables live tracking of proliferating human cells. The reporter hiPSC line successfully differentiated into cardiomyocytes (CMs), endothelial cells (ECs), and fibroblasts (FBs), with eGFP+ cells identifying actively dividing populations across lineages. Each cell type exhibited appropriate lineage-specific marker expression and high differentiation efficiency. Importantly, the cyclinB1-eGFP system allowed real-time identification and tracking of proliferating (eGFP+) cells within these differentiated populations. This tool provides an innovative platform for screening potential pro-proliferative compounds, facilitating the discovery of novel therapies to stimulate or inhibit cell division.

PMID:40694867 | DOI:10.1016/j.scr.2025.103776

Am J Stem Cells. 2025 Jun 15;14(2):53-72. doi: 10.62347/YGXA7976. eCollection 2025.

ABSTRACT

Mesenchymal stem cells (MSCs) are a type of pluripotent stem cells originating from the mesoderm, known for their capability to differentiate into various specific tissue cell types and fulfill corresponding physiological roles. Furthermore, MSCs are essential in modulating the tissue microenvironment through the release of soluble factors that can modify the local inflammatory conditions of injured tissues. As a result, MSCs show considerable promise for therapeutic use in a range of traumatic scenarios, including but not limited to liver damage, myocardial infarction, neurological conditions, lung trauma, kidney injuries, and disorders affecting the female reproductive system. They play a key role in alleviating cell apoptosis, sustaining cell survival, encouraging proliferation, enhancing the inflammatory milieu, minimizing tissue fibrosis, and supporting vascular regeneration. These mechanisms are crucial for controlling excessive and persistent inflammatory reactions that arise after organ injury, which may lead to cell death and hindered blood circulation, ultimately causing fibrosis and weakened organ functionality. Additionally, MSCs are gradually being incorporated into clinical settings, where careful considerations regarding methods of administration, dosing, safety, and effectiveness are vital for achieving optimal clinical results. This review provides an overview of the mechanisms by which mesenchymal stem cells aid in the repair of major bodily organs. We also examine their current status, obstacles, and pertinent issues concerning clinical applications.

PMID:40686745 | PMC:PMC12267123 | DOI:10.62347/YGXA7976