Terapia celular

MedComm (2020). 2025 Oct 4;6(10):e70407. doi: 10.1002/mco2.70407. eCollection 2025 Oct.

ABSTRACT

The substantial loss of cardiomyocytes resulting from myocardial infarction leads to pathological remodeling of the heart and the onset of heart failure. Promoting heart regeneration is therefore a critical therapeutic goal for repairing damaged cardiac tissue. Over the past two decades, the utilization of cardiac stem cells for heart regeneration has emerged as a focal point of research. However, the related mechanisms and efficacy remain constrained by poor integration and survival. Concurrently, genetic lineage tracing has definitively shown that the adult mammalian heart lacks significant endogenous stem cells. It is now widely accepted that heart regeneration primarily arises from the proliferation of pre-existing adult cardiomyocytes. This review systematically summarizes the physiological and microenvironmental changes during the developmental process of cardiomyocytes, elucidates the intrinsic and extrinsic molecular biological mechanisms that regulate cardiomyocyte proliferation, and discusses exogenous cell transplantation therapy, potentially endogenous pharmacological and genetic approaches, as well as promising bioengineering and cross-disciplinary methods. By synthesizing these multifaceted advances, this review aims to clarify important issues that require further elucidation in this field, thereby advancing the depth of research on heart regeneration and its clinical translational applications.

PMID:41049268 | PMC:PMC12495452 | DOI:10.1002/mco2.70407

Histochem Cell Biol. 2025 Oct 4;163(1):94. doi: 10.1007/s00418-025-02426-w.

ABSTRACT

Coenzyme Q10 (CoQ10) is an antioxidant known for its potential protective effects against various types of cardiac injury. The aim of this study was to determine the protective effects of CoQ10 on cardiomyocytes, telocytes and progenitor cells in rats with isoproterenol (ISO)-induced cardiotoxicity. A total of 60 Sprague-Dawley rats were divided into six groups (n = 10): Group I: control, Group II: saline control, Group III: oil control, Group IV: ISO, Group V: CoQ10, Group VI: ISO and CoQ10. Isoproterenol was administered intraperitoneally at a dose of 85 mg/kg twice on the eighth and ninth days, and CoQ10 was administered by oral gavage at a daily dose of 20 mg/kg. Heart tissue samples were collected and analysed at the end of the study. CoQ10 reduced ISO-induced cardiac degeneration, necrosis, inflammatory infiltration and fibrosis. The stimulation of cell cycle activators such as histone H3 and proliferating cell nuclear antigen (PCNA) was found to play a role in the repair of cardiac injury in the cardiomyocytes known to be postmitotic. An increase in c-Kit and CD34 stem cells was seen with the beneficial effect of CoQ10 (P < 0.05). The presence of telocytes, which play an important role in cardiac regeneration, was visualised by double CD34-c-Kit and CD34-vimentin immunofluorescence staining. The results indicate that CoQ10, through its antioxidant effect, ameliorates cardiac lesions caused by ISO, induces a limited number of cell cycle activators in cardiomyocytes and interstitial cells and has a positive effect on the increase of progenitor cells in the heart.

PMID:41046280 | DOI:10.1007/s00418-025-02426-w

J Dent Sci. 2025 Oct;20(4):2066-2075. doi: 10.1016/j.jds.2025.05.014. Epub 2025 May 29.

ABSTRACT

Currently, the concept of regeneration and regenerative therapies are already being applied clinically to treat pulpal and periodontal diseases, as well as to repair and regenerate systemic organs and tissues. During wound healing, well-developed, functional vascular networks and revascularization are fundamental factors in restoring regenerative potential. Growth factors, stem cells, and scaffolds alone or in combination are reported to contribute to successful tissue repair and engineering via cell transplantation, cell homing or other technologies. Among the growth factors, basic fibroblast growth factor (bFGF) has been found to regulate the proliferation, stemness, migration, and differentiation of vascular and mineralized tissues into various cell types through the differential activation of FGF receptors (FGFRs) and downstream signaling pathways. In addition to growth factors, various dental stem cells are widely used for the regeneration of diseased or lost dental pulp and periodontal tissues, yielding promising results. Stem cells from the apical papilla (SCAPs) and dental pulp stem cells (DPSCs), with or without bFGF, have been shown to be crucial for angiogenesis/revascularization, neuronal growth, and the repair/regeneration of the pulpo-dentin complex, apexogenesis, and may potentially be used in the future to treat various systemic diseases such as myocardial infarction, diabetes, retinopathy, and others. Further studies are needed to optimize the use of bFGF and dental stem cells such as SCAPs and DPSCs by using cell transplantation, cell homing or other technologies for tissue and organ regeneration in experimental animal models and, eventually, in clinical patients in the future.

PMID:41040621 | PMC:PMC12485421 | DOI:10.1016/j.jds.2025.05.014

Exp Mol Med. 2025 Oct 1. doi: 10.1038/s12276-025-01549-3. Online ahead of print.

ABSTRACT

Therapeutic interventions to replenish lost cardiomyocytes and recover myocardium functions following ischemic myocardial infarction (MI) remain major goals in the cardiac regeneration field. Clinical trials harnessing autologous or allogeneic cell therapy approaches from both cardiac and noncardiac cells sources, thus far, demonstrate marginal improvement. Moreover, complications such as arrythmias and graft rejections associated with cellular or organ-based therapies continue to prevail. Extracellular vesicles, on the other hand, are cell-derived, nano-sized, cargo-containing biomolecules that have emerged as potent alternatives to cell-based cardiac regeneration/replacement therapy. Recent studies demonstrate that most stem-cell-derived extracellular vesicles (Stem-EVs) are nonimmunogenic and carry cardioprotective therapeutic cargos. Moreover, administration of multiple Stem-EV types in animal models of acute MI results in reduced inflammation, apoptosis, smaller infarct size and improved cardiac functionality. With recent developments, engineered Stem-EVs with enhanced cardiac targeting, prolonged circulation and recombinant therapeutic cargos may tilt the cardiac regeneration field toward these novel cell-free biologics. Here we provide a brief overview of current approaches to repair and replenish damaged cardiomyocytes following MI via cell therapy and in vivo reprogramming, and we delve deeply into the therapeutic potentials of Stem-EVs in cardiac repair and regeneration.

PMID:41034526 | DOI:10.1038/s12276-025-01549-3

Circ Res. 2025 Oct 1. doi: 10.1161/CIRCRESAHA.125.326522. Online ahead of print.

ABSTRACT

BACKGROUND: Induction of cardiomyocyte proliferation in situ represents a promising strategy for myocardial regeneration following injury. However, cardiomyocytes possess intrinsic inhibitory mechanisms that attenuate pro-proliferative signaling and constrain their expansion. We hypothesized that cell-cell contact is a key suppressor of cardiomyocyte proliferation. We aimed to delineate the underlying molecular pathways to enable sustained proliferation in 3-dimensional contexts.

METHODS: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were cultured at varying plating densities to examine the impact of cell-cell contact on cell cycle activity. Phosphoproteomic profiling was performed in sparse versus dense cultures to identify signaling alterations. Conditioned media from sparse cultures were interrogated using a human growth factor array to identify secreted pro-proliferative factors.

RESULTS: hiPSC-CM proliferation increased proportionally with plating density until intercellular contacts were established, at which point proliferation was suppressed. Dense cultures exhibited enhanced adherens junction assembly, sarcomeric organization, and contractile function. Increased cell-cell contact in dense conditions attenuated nuclear translocation of β-catenin and reduced TCF/LEF transcriptional activity, providing a mechanistic basis for the reduced hiPSC-CM proliferation. Disruption of adherens junctions or sarcomere assembly via siRNA-mediated knockdown of N-cadherin or α-actinin, respectively, resulted in increased cell cycle activation of hiPSC-CMs, but this was not sufficient to drive division of hiPSC-CMs. Additional screening for putative secreted growth factors in the conditioned media from sparsely plated hiPSC-CMs revealed the enrichment of IGFBP2, which was sufficient to drive hiPSC-CM division in the presence of cell-cell contact in 3-dimensional constructs.

CONCLUSIONS: Our findings demonstrate that cell-cell contact inhibits hiPSC-CM proliferation through adherens junction formation, sarcomeric assembly, and reduced IGFBP2 secretion. Importantly, exogenous supplementation of IGFBP2 can overcome cell contact-mediated inhibition of hiPSC-CM proliferation and facilitate the growth of 3-dimensional cardiac tissue. These insights provide valuable implications for advancing cardiac tissue engineering and regenerative therapies.

PMID:41031396 | DOI:10.1161/CIRCRESAHA.125.326522

Biomaterials. 2025 Sep 20;327:123727. doi: 10.1016/j.biomaterials.2025.123727. Online ahead of print.

ABSTRACT

Up to 1 billion cardiomyocytes (CMs) die during myocardial infarction (MI), leading to permanent muscle loss and devasting functional impacts. Biomaterial therapies have aimed to passively reinforce the infarcted left ventricle (LV), but their therapeutic impact remains limited as they fail to directly address the loss of functional CMs. In this work, we employed a simulation-guided workflow to design an optimized biomaterial support that can be combined with contractile CMs for implantation after MI. A finite element model (FEM) of the LV post-MI was developed and showed longitudinal reinforcement and active contractility improves ejection fraction (EF) post-MI (+3.39 % and +14.97 %, respectively). To this end, we developed a coordinated remuscularization-reinforcement therapy using engineered human myocardium (EHM) composed of human induced pluripotent stem cell-derived CMs (hiPSC-CMs) integrated with a highly aligned electrospun polycaprolactone (PCL) scaffold. Remuscularization (EHM-only), reinforcement (PCL-only) and its coordinated therapy (PCL-EHM) were evaluated in a rat model of MI. We report successful engraftment of the implants onto the heart with significant maturation of hiPSC-CMs after four weeks in vivo (∼7-fold increase of cTnT area and ∼2-fold increase MLC2v area compared to in vitro cultured controls). Using 4D ultrasound (US), we quantified 3D regional strains and found that the benefits of PCL reinforcement on maintaining LV structure and function were additive with remuscularization by EHM. This additive effect was reflected inimproved regional strain after injury when PCL and EHM were delivered as a composite therapy. This work establishes a promising strategy for synergistic reinforcement and remuscularization of the infarcted heart.

PMID:41016348 | DOI:10.1016/j.biomaterials.2025.123727

Bioengineering (Basel). 2025 Sep 11;12(9):970. doi: 10.3390/bioengineering12090970.

ABSTRACT

Orofacial Mesenchymal Stem Cells (OMSCs) are an attractive and promising tool for tissue regeneration, with their potential for craniofacial bone repair being a primary focus of research. A key advantage driving their clinical interest is their accessibility from tissues that are often discarded, such as exfoliated deciduous teeth, which circumvents the ethical concerns and donor site morbidity associated with other stem cell sources. The high proliferation ability and multi-differentiation capacity of OMSCs make them a unique resource for tissue engineering. Recently, OMSCs have been explored in the restoration of the heart and skin, treatment of oral mucosal lesions, and regeneration of hard connective tissues such as cartilage. Beyond their direct regenerative capabilities, OMSCs possess potent immunomodulatory functions, enabling them to regulate the immune system in various inflammatory disorders through the secretion of cytokines. This review offers an in-depth update regarding the therapeutic possibilities of OMSCs, highlighting their roles in the regeneration of bone and various tissues, outlining their immunomodulatory capabilities, and examining the essential technologies necessary for their clinical application.

PMID:41007215 | PMC:PMC12467435 | DOI:10.3390/bioengineering12090970

Front Pharmacol. 2025 Sep 10;16:1667140. doi: 10.3389/fphar.2025.1667140. eCollection 2025.

ABSTRACT

Myocardial infarction (MI) remains a leading cause of cardiovascular mortality despite advances in reperfusion strategies, necessitating innovative therapeutic approaches. Human umbilical cord mesenchymal stem cell-derived exosomes (HUCMSCs-Exos) have emerged as promising next-generation therapeutics, offering superior advantages including enhanced stability, reduced immunogenicity, and ability to cross biological barriers compared to cellular therapies. These naturally occurring nanovesicles exert comprehensive cardioprotective effects through multifaceted mechanisms encompassing anti-apoptotic signaling, angiogenesis promotion, immunomodulation, anti-fibrotic activity, oxidative stress reduction, and cardiac regeneration enhancement. The therapeutic arsenal includes diverse molecular cargo such as microRNAs (miR-29b, miR-133a-3p, miR-24-3p), long non-coding RNAs, circular RNAs, and bioactive proteins that synergistically target key pathophysiological processes in MI. Advanced engineering approaches, including genetic modification, surface functionalization, and biomaterial integration, have further enhanced therapeutic efficacy through targeted delivery and sustained release systems. While preclinical studies demonstrate significant cardioprotective effects, clinical translation faces challenges in standardization, manufacturing scalability, and regulatory approval. The convergence of innovative engineering strategies, personalized medicine approaches, and emerging technologies positions HUCMSCs-Exos as promising therapeutic approach that could fundamentally alter MI treatment paradigms and improve global cardiovascular health outcomes.

PMID:41001344 | PMC:PMC12457780 | DOI:10.3389/fphar.2025.1667140

Elife. 2025 Sep 23;13:RP100248. doi: 10.7554/eLife.100248.

ABSTRACT

The Hippo pathway controls organ development, homeostasis, and regeneration primarily by modulating YAP/TEAD-mediated gene expression. Although emerging studies report Hippo-YAP dysfunction after viral infection, it is largely unknown in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we analyzed RNA sequencing data from human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and SARS-CoV-2-infected human lung samples, and observed a decrease in YAP target gene expression. In screening SARS-CoV-2 nonstructural proteins, we found that nonstructural protein 13 (NSP13), a conserved coronavirus helicase, inhibits YAP transcriptional activity independent of the upstream Hippo kinases LATS1/2. Consistently, introducing NSP13 into mouse cardiomyocytes suppresses an active form of YAP (YAP5SA) in vivo. Subsequent investigations on NSP13 mutants revealed that NSP13 helicase activity, including DNA binding and unwinding, is crucial for suppressing YAP transactivation in HEK293T cells. Mechanistically, TEAD4 serves as a platform to recruit NSP13 and YAP. NSP13 likely inactivates the YAP/TEAD4 transcription complex by remodeling chromatin to recruit proteins, such as transcription termination factor 2 (TTF2), to bind the YAP/TEAD/NSP13 complex. These findings reveal a novel YAP/TEAD regulatory mechanism and uncover molecular insights into Hippo-YAP regulation after SARS-CoV-2 infection in humans.

PMID:40985618 | PMC:PMC12456957 | DOI:10.7554/eLife.100248

Mater Today Bio. 2025 Aug 29;34:102256. doi: 10.1016/j.mtbio.2025.102256. eCollection 2025 Oct.

ABSTRACT

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) hold promise in averting the development of heart failure with reduced ejection fraction (HFrEF) following myocardial infarction (MI) by potentially regenerating the infarcted myocardium and restoring left ventricular contractility. However, challenges remain regarding the structural and functional maturation states of these cells, as well as their retention and integration into the myocardium. Here, we developed a novel three-dimensional cardiac patch and evaluated its potential to instigate cardiac regeneration. For the first time, melt electrowriting (MEW) was utilised to fabricate reproducible, structurally anisotropic, and handleable scaffolds from high molecular weight, medium chain-length polyhydroxyalkanoates (MCL-PHAs). These MEW-PHA scaffolds maintained hPSC-CMs, facilitating their rapid structural maturation and functional improvement in vitro. Different combinations of hPSC-derived cardiovascular cells were seeded onto the MEW-PHA scaffolds and stacked to create synchronously beating, multi-scaffold cardiac patches. These were well-accepted in a murine MI model without capsule formation. Notably, cardiac patches containing hPSC-derived cardiac microvascular-like endothelial cells (hPSC-CMVECs) initiated vascular regeneration within the infarcted myocardium. This novel advancement enabled the reproducible fabrication of high molecular weight MCL-PHA-based MEW cardiac patches that matured hPSC-CMs and promoted vascular regeneration, offering potential for future improvement in post-MI cardiac function through enhanced hPSC-CM retention.

PMID:40977832 | PMC:PMC12446554 | DOI:10.1016/j.mtbio.2025.102256

Cell Stem Cell. 2025 Oct 2;32(10):1563-1576.e11. doi: 10.1016/j.stem.2025.08.015. Epub 2025 Sep 17.

ABSTRACT

Adult mammalian hearts are non-regenerative, and a majority of studies examining repair and potential regeneration post-myocardial infarction (MI) have focused on cardiomyocyte (CM) proliferation and infarcted zones. Here, we observed aberrantly high expression of lysozyme 2 (Lyz2) in injured mouse hearts at both local injury sites and at remote zones, with sustained Lyz2 expression conspicuous in endocardial cells of non-regenerative hearts. Although traditionally conceptualized as a myeloid marker, we demonstrate that LYZ2 functions as an injury-specific, positive regulator of lysosomal degradation capacity that mediates pathogenic degradation of the extracellular matrix. We observed an anti-apoptotic benefit to CMs upon disrupting LYZ2/LYZ function in mice and in a human endomyocardium experimental model. Harnessing these insights, we show that both Lyz2 knockout (KO) and pharmacological inhibition of lysosomal degradation confer rapid functional recovery in injured non-regenerative hearts. Thus, targeting a remote injury response in a non-CM cell type rapidly promotes post-MI recovery of non-regenerative hearts.

PMID:40967223 | DOI:10.1016/j.stem.2025.08.015

Circ Res. 2025 Sep 26;137(8):1117-1132. doi: 10.1161/CIRCRESAHA.125.326758. Epub 2025 Sep 3.

ABSTRACT

BACKGROUND: In response to cardiac injury the mammalian heart undergoes ventricular remodeling to maintain cardiac function. These changes are initially considered compensatory, but eventually lead to increased cardiomyocyte apoptosis, reduced cardiac function and fibrosis which are important contributors to the development of heart failure. The small GTPase Sept4 (Septin4) has previously been implicated in the regulation of regeneration and apoptosis in several organs. However, the role of Sept4 in regulating the response of the heart to stress is unknown.

METHODS: Ten-week-old wild-type (WT) and Sept4 knockout mice were subjected to transverse aortic constriction to induce cardiac injury. Genotype-dependent differences were investigated at baseline and at 1- and 4-week postinjury time points. To definitively establish the fibroblast-specific cardioprotective effects of Sept4, we generated a fibroblast-specific Sept4 conditional knockout model.

RESULTS: Under homeostatic conditions Sept4 knockout mice showed normal cardiac function comparable with WT controls. In response to transverse aortic constriction, WT mice developed reduced cardiac function and heart failure, accompanied by an increase in cardiomyocyte apoptosis. In contrast, knockout mice were protected against injury with maintenance of normal cardiac function and reduced levels of cardiomyocyte apoptosis. Both at baseline and after transverse aortic constriction, knockout hearts exhibited decreased levels of cardiac extracellular matrix deposition and fibrosis compared with WT controls. In support of these data, the level of myofibroblast activation was lower after injury in knockout mice. Furthermore, the knockout group showed higher levels of cardiac compliance and improved diastolic function compared with WT controls. Mechanistically, we identified reduced fibrosis development due to alterations in calcineurin-dependent signaling in fibroblasts. These results were further verified in fibroblast-specific conditional Sept4 knockout mice subjected to cardiac pressure overload.

CONCLUSIONS: We identified Sept4 as an important regulator of extracellular matrix remodeling in the heart. Sept4 controls the conversion of fibroblast to myofibroblast through calcineurin-dependent mechanisms.

PMID:40960950 | PMC:PMC12466173 | DOI:10.1161/CIRCRESAHA.125.326758

World J Cardiol. 2025 Aug 26;17(8):107437. doi: 10.4330/wjc.v17.i8.107437.

ABSTRACT

Mesenchymal stem cells (MSCs) possess unique properties such as immunomodulation, paracrine actions, multilineage differentiation, and self-renewal. Therefore, MSC-based cell therapy is an innovative approach to treating various degenerative illnesses, including cardiovascular diseases. However, several challenges, including low transplant survival rates, low migration to the ischemic myocardium, and poor tissue retention, restrict the application of MSCs in clinical settings. These undesirable cell therapy outcomes mainly originated due to the overproduction of reactive oxygen species (ROS) in the injured heart. MSCs' stress-coping capacity can be enhanced by preconditioning them under conditions similar to the microenvironment of wounded tissues. Hydrogen peroxide (H2O2) is a ROS that has been shown to activate protective cellular mechanisms such as survival, proliferation, migration, paracrine effects, and differentiation at sublethal doses. These processes are induced via phosphatidylinositol 3-kinase/protein kinase B, p38 mitogen-activated protein kinases, c-Jun N-terminal kinase, Janus kinase/signal transducer and activator of the transcription, Notch1, and Wnt signaling pathways. H2O2 preconditioning could lead to many clinical benefits, including ischemic injury reduction, enhanced survival of cellular transplants, and tissue regeneration. In this review, we present an overview of stem cell preconditioning methods and the biological functions activated by H2O2 preconditioning. Furthermore, this review explores the molecular mechanisms underlying the protective cellular functions stimulated under H2O2 preconditioning.

PMID:40949936 | PMC:PMC12426982 | DOI:10.4330/wjc.v17.i8.107437

Elife. 2025 Sep 12;14:RP107148. doi: 10.7554/eLife.107148.

ABSTRACT

Tissue regeneration enhancer elements (TREEs) direct expression of target genes in injured and regenerating tissues. Additionally, TREEs of zebrafish origin were shown to direct expression of transgenes in border zone regions after cardiac injury when packaged into recombinant adeno-associated viral (AAV) vectors and introduced into mice. Future implementation of TREEs into AAV-based vectors as research tools and potential gene therapy modalities requires a deeper understanding of expression dynamics and potential off-target effects. Here, we applied in vivo bioluminescent imaging to mice systemically injected with AAV vectors containing different combinations of capsids, enhancers, and timing of delivery. Longitudinal tracking of expression directed by different TREEs revealed distinct amplitudes and durations of reporter gene expression in the injured heart. The liver-de-targeted AAV capsid, AAV.cc84, could deliver TREEs either pre- or post-cardiac injury to negate off-target expression in the liver while maintaining transduction in the heart. By screening AAV9-based capsid libraries dosed systemically in mice post-cardiac injury, we discovered a new capsid variant, AAV.IR41, with enhanced transduction in cardiac injuries and with elevated transduction of TREE-driven transgenes versus conventional AAV9 vectors. In vivo bioluminescence imaging offers insights into how enhancers and engineered capsids can be implemented to modulate spatiotemporal transgene expression for targeted therapies.

PMID:40938325 | PMC:PMC12431772 | DOI:10.7554/eLife.107148

J Adv Res. 2025 Sep 9:S2090-1232(25)00694-0. doi: 10.1016/j.jare.2025.09.011. Online ahead of print.

ABSTRACT

INTRODUCTION: Aortic stenosis (AS) involves aortic obstruction, pressure overload, reduced cardiac output, and impaired organ arterial hemodynamics. Many patients remain at risk of rehospitalization or death after transcatheter aortic valve replacement (TAVR) due to unclear mechanisms. Our previous studies linked bile acids (BAs) metabolism to heart-other organ crosstalk, but the BAs-hemodynamics interplay in AS remains unclear.

OBJECTIVES: To investigate metabolic abnormalities in AS, focusing on the role of BA metabolism in AS pathogenesis and the underlying mechanisms.

METHODS: An acute canine model of AS was established via intra-aortic balloon catheter-induced transverse aortic obstruction (ITAO). Computational fluid dynamics (CFD) simulation was performed to assess the arterial hemodynamics of the aorta and other organs. Untargeted/targeted metabolomics and transcriptomics were performed in ITAO and deleting ITAO (deITAO) canines. The findings were validated in 33 controls and 30 AS patients. Metabolic predictive performance was assessed by the area under the receiver operating characteristic (AUROC) curve. Transcriptomic and western blot analyses were used to assess the effects of glycoursodeoxycholic acid (GUDCA) and glycoursodeoxycholic acid 3 sulfate sodium (GUDCA-3S) on isoproterenol (ISO)-induced myocardial remodeling.

RESULTS: ITAO replicated AS hemodynamics (reduced cardiac output, increased aortic velocity), reversed post-deITAO. CFD revealed that ITAO increased organ (e.g., liver) artery pressure, improved after deITAO. Untargeted metabolomics identified 1583 differentially abundant metabolites; transcriptomics revealed 291 DEGs enriched in BA biosynthesis. Targeted BA analysis revealed that GUDCA-3S was elevated in ITAO canines, correlated with aortic velocity (R = -0.4822, P = 0.0002) and BNP (R = 0.3836, P = 0.0019) in AS patients, and exhibited superior AS diagnostic performance (AUROC = 0.844, P < 0.001). Reduced aortic flow upregulated hepatic SULT2A1, driving GUDCA sulfonation to GUDCA-3S and weakening GUDCA's cardioprotection by impairing IL-17/NF-κB signaling inhibition in ISO-induced cardiomyocytes.

CONCLUSIONS: BA metabolism dysfunction responds to cardiac hemodynamic changes, with GUDCA-3S linking cardiac hemodynamics and BA metabolism in AS.

PMID:40934971 | DOI:10.1016/j.jare.2025.09.011

Mol Biol Rep. 2025 Sep 10;52(1):880. doi: 10.1007/s11033-025-11001-4.

ABSTRACT

Regenerative cardiology has emerged as a novel strategy to improve cardiac healing following ischemic injury. While stem-cell-mediated cardiac regeneration has garnered much attention as a promising strategy, its value remains debated owing to the lack of ideal stem cell source candidates. Resident/endogenous cardiac-derived stromal cells (CSCs) exhibit superior therapeutic potential due to their innate abilities to differentiate into cardiac cells, especially cardiomyocytes (CM). Emerging research has highlighted diverse endogenous CSCs phenotypes and sub-types as candidates for cardiac repair. Interestingly, CSCs promote healing through angiogenesis and regenerative paracrine signaling along with replenishing CM, and CM-like cells in the ischemic heart. Unfortunately, the clonogenic properties and translational potential of CSCs are minimally explored. This review examines the healing promise of a myriad CSCs such as c-kit + cardiac cells, Sca-1 + cells, cardiosphere-derived cells, side population cells, Bm1 + cells, cardiac atrial appendage cells, cardiac adipose cells, epicardial cells, and Isl1 + cells. Also, the review highlights the areas of improvement regarding the therapeutic applications of CSC to extrapolate into the clinical arena of cardiac management.

PMID:40928598 | PMC:PMC12423225 | DOI:10.1007/s11033-025-11001-4

Adv Pharm Bull. 2025 Jun 16;15(2):268-283. doi: 10.34172/apb.025.45122. eCollection 2025 Jul.

ABSTRACT

PURPOSE: Myocardial infarction (MI), the leading cause of human mortality, is induced by a sudden interruption of blood supply. Among various stem cell types, endothelial progenitor cells (EPCs) are novel and valid cell sources for the restoration of vascularization in the ischemic tissue. The present study aimed to evaluate the regenerative properties of EPCs in rodent models of MI.

METHODS: A comprehensive systematic search was implemented in Cochrane Library, Embase, PubMed, Scopus, and Web of Science databases without language limitation in Sep 2024. Of the 67 papers pooled, 42 met the inclusion criteria and were subjected to multiple analyses.

RESULTS: Compared to the MI group, the overall effect size was confirmed in the groups receiving EPC with enhanced angiogenesis (SMD: 2.02, CI 95%: 1.51-2.54, P<0.00001; I2: 82%), reduced fibrosis (SMD: -1.48; 95% CI-2.15, -0.81; P<0.0001; I2: 88%), improved ejection fraction (EF; SMD: 1.72; 95% CI-1.21, 2.23; P<0.00001; I2: 87%), and fractional shortening (FS; SMD: 1.58; 95% CI-1.13, 2.03; P<0.00001; I2: 82%). Data confirmed significant improvements in the cardiac tissue parameters after intramyocardial injection of EPCs.

CONCLUSION: These data showed that EPC transplantation is an alternative therapy to ameliorate ischemic myocardium in rodents via the stimulation of angiogenesis, reduction of fibrosis, and improvement of fractional shortening and ejection fraction.

PMID:40922747 | PMC:PMC12413962 | DOI:10.34172/apb.025.45122

Expert Opin Investig Drugs. 2025 Sep;34(9):675-683. doi: 10.1080/13543784.2025.2558655. Epub 2025 Sep 10.

ABSTRACT

INTRODUCTION: Ischemic heart disease (IHD) constitutes the most prevalent form of cardiac disease in the general population. Although current therapeutic interventions have significantly improved both quality of life and survival rates, no available treatment can reverse the loss of cardiomyocytes resulting from ischemic injury. Existing therapies are limited to attenuating myocardial damage, reducing its extent, and mitigating its clinical consequences.

AREA COVERED: Advances in pharmacological and biomedical research have paved the way for novel therapeutic modalities. Tissue engineering, gene therapy, microRNAs (miRNAs), small interfering RNAs (siRNAs), and stem cell-based approaches represent promising avenues for promoting myocardial regeneration. In the present review, we aim to provide a succinct yet comprehensive review of the principal areas of current scientific investigation in this evolving field.

EXPERT OPINION: Although current scientific evidence remains limited, primarily due to the lack of large-scale clinical trials in vivo, the prospects of these therapeutic strategies are highly promising, particularly for patients with limited conventional treatment options. It remains to be determined when and how these approaches may be effectively implemented in clinical practice.

PMID:40914985 | DOI:10.1080/13543784.2025.2558655

Int J Artif Organs. 2025 Sep;48(9):627-635. doi: 10.1177/03913988251370227. Epub 2025 Sep 5.

ABSTRACT

Cardiovascular disease (CVD) is a leading cause of death worldwide. CVD includes conditions such as myocardial infarction (MI), arrhythmias, valvular heart disease, and cardiomyopathy. The limitations of heart treatment are related to the inability of damaged cells to regenerate, which leads to an increasing demand for new therapies. Cardiac tissue engineering (CTE) aims to efficiently regenerate damaged cardiac tissues by combining cells and biomaterials to address these diseases. Various cell types have been used in CTE research, including adult and pluripotent stem cells, the latter differentiating into functional cardiomyocytes. An ideal biomaterial promotes efficient adhesion, growth, and differentiation of cardiac cells and possesses the appropriate characteristics needed for functional cardiac cells, showing great potential for heart repair and regeneration. This review focuses on various tissue engineering approaches for the regeneration and repair of cardiac tissues following myocardial infarction.

PMID:40913305 | DOI:10.1177/03913988251370227

Biotechnol J. 2025 Sep;20(9):e70116. doi: 10.1002/biot.70116.

ABSTRACT

Cardiac tissue engineering (CTE) is a rapidly evolving field that combines cells, scaffolds, and biofabrication methods to repair damaged heart tissue. New technologies have made it possible to utilize AI in designing cardiac patches and 4D bioprinting to create biomaterials that respond to time. These procedures are a big step forward from traditional ones since they offer more accuracy, flexibility, and the possibility of therapies that are tailored to each patient. This review talks about the latest developments in cellular sources, biomaterials, and bioprinting platforms, as well as immunological, regulatory, and translational issues. We show a realistic way forward for using CTE in clinical settings by looking at both its strengths and weaknesses. SUMMARY: Innovative biomaterials enhance cardiac tissue regeneration. 3D bioprinting revolutionizes cardiac tissue fabrication. Patient-specific stem cell therapies offer personalized solutions. AI and 4D printing advance tissue design and clinical applications.

PMID:40911173 | DOI:10.1002/biot.70116