Terapia celular

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Peripheral Artery Disease and Antithrombotic Management: A Global Perspective on Efficacy, Safety, and Access

Jue, 06/26/2025 - 10:00

Cardiol Rev. 2025 Jun 26. doi: 10.1097/CRD.0000000000000989. Online ahead of print.

ABSTRACT

Peripheral artery disease (PAD) is a severe manifestation of systemic atherosclerosis, affecting over 230 million individuals worldwide and leading to both limb-threatening ischemia and catastrophic cardiovascular events. This progression is driven in part by thrombosis, which arises from complex interactions of endothelial dysfunction, platelet activation, and thrombin generation. These processes culminate in acute limb ischemia, major amputations, and myocardial infarction. Antithrombotic therapy is fundamental to PAD management, with antiplatelet monotherapy (aspirin or clopidogrel) remaining first-line for symptomatic patients. However, the paradigm has shifted with dual-pathway inhibition (DPI), combining low-dose rivaroxaban (2.5 mg twice daily) with aspirin, which reduces major adverse cardiovascular events by 24% and limb events by 46%, particularly in high-risk subgroups including postrevascularization or chronic limb-threatening ischemia patients. Despite these advances, bleeding risks (eg, gastrointestinal hemorrhage with DPI) and global disparities in access to therapies pose significant challenges. Current guidelines now stratify recommendations by risk: the American Heart Association/American College of Cardiology endorses DPI for postrevascularization (class IIa), while the European Society of Cardiology reserves it for recurrent ischemia (class IIb). Emerging strategies target residual inflammatory risk (eg, colchicine) and vascular regeneration (stem cell therapy), yet cost and scalability limit widespread adoption, especially in developing nations bearing 70% of the PAD burden. The future of PAD care demands personalized approaches that integrate antithrombotic efficacy, bleeding mitigation, and socioeconomic realities. Further research is needed to refine risk stratification, expand access to DPI, and develop adjunctive therapies for this growing global health crisis.

PMID:40569059 | DOI:10.1097/CRD.0000000000000989

Categorías: Terapia celular

The Role of the Extracellular Matrix in Inducing Cardiac Cell Regeneration and Differentiation

Mié, 06/25/2025 - 10:00

Cells. 2025 Jun 10;14(12):875. doi: 10.3390/cells14120875.

ABSTRACT

The adult human heart has a limited ability to regenerate after injury, leading to the formation of fibrotic scars and a subsequent loss of function. In fish, mice, and humans, cardiac remodeling after myocardial injury involves the activation of epicardial and endocardial cells, pericytes, stem cells, and fibroblasts. The heart's extracellular matrix (ECM) plays a significant role in the regeneration and recovery process. The epicardium, endocardium, and pericytes reactivate the embryonic program in response to ECM stimulation, which leads to epithelial-mesenchymal transition, cell migration, and differentiation. This review analyzes the role of ECM in guiding the differentiation or dedifferentiation and proliferation of heart components by comparing significant findings in a zebrafish model with those of mammals.

PMID:40558502 | PMC:PMC12191243 | DOI:10.3390/cells14120875

Categorías: Terapia celular

Cullin-associated and neddylation-dissociated protein 1 (CAND1) promotes cardiomyocyte proliferation and heart regeneration by enhancing the ubiquitinated degradation of Mps one binder kinase activator 1b (Mob1b)

Mar, 06/24/2025 - 10:00

Cell Death Differ. 2025 Jun 24. doi: 10.1038/s41418-025-01540-5. Online ahead of print.

ABSTRACT

Activation of the intrinsic regenerative potential of adult mammalian hearts by promoting cardiomyocyte proliferation holds great potential in heart repair. CAND1 (Cullin-associated and neddylation-dissociated protein 1) functions as a critical regulator of cellular protein homeostasis by fine-tuning the ubiquitinated degradation of specific abnormally expressed protein substrates. Here, we identified that cardiac-specific transgenic overexpression of CAND1 reduced the infarct size, restored cardiac function, and promoted cardiomyocyte proliferation after myocardial infarction in juvenile (7-day-old) and adult (8-week-old) mice. Conversely, CAND1 deficiency blunted the regenerative capacity of neonatal hearts after apex resection. MS and functional verification demonstrated that CAND1 enhanced the assembly of Cullin1, FBXW11(F-box/WD repeat-containing protein 11), and Mob1b (Mps one binder kinase activator 1b) complexes, and thus promotes the degradation of Mob1b. The ubiquitination of Mob1b occurred at K108 and was linked by K48 of ubiquitin. Mob1b deletion partially rescued the loss of regenerative capacity in neonatal hearts induced by CAND1 deficiency and improved cardiac function in adult mice post-MI. Moreover, CAND1 promoted the proliferation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Our data demonstrate that CAND1 promotes cardiomyocyte proliferation via FBXW11-mediated K48-linked ubiquitination degradation of Mob1b, and improves heart regeneration after cardiac injury. The findings provide a novel strategy to promote cardiac regeneration and repair. Schematic diagram of the role of CAND1 in regulating ubiquitination and degradation of Mob1b and cardiomyocyte proliferation and heart regeneration. Under CAND1-High condition, CAND1 promotes the incorporation of Cullin1, FBXW11, and Mob1b complexes, and accelerates SCFFBXW11-mediated K48-linked ubiquitination of Mob1b at the K108 site, which leads to the degradation of Mob1b and thus suppresses the Hippo signaling pathway and facilitates cardiomyocyte proliferation and heart regeneration post-MI.

PMID:40555744 | DOI:10.1038/s41418-025-01540-5

Categorías: Terapia celular

Cardiac Regeneration From Scar to Syncytium: Mitigating the Formation of Scar Tissue

Mié, 06/18/2025 - 10:00

Cardiol Rev. 2025 Jun 18. doi: 10.1097/CRD.0000000000000972. Online ahead of print.

ABSTRACT

Myocardial infarction and heart failure remain among the leading global causes of morbidity and mortality, mainly due to the irreversible loss of cardiomyocytes and the human heart's inherently limited regenerative capacity. Cardiac regeneration has emerged as a transformative frontier in cardiovascular medicine in response to this clinical and biological impasse. This review examines current approaches to rebuilding damaged heart tissue and improving cardiac function. Early investigations into cell-based therapies, particularly mesenchymal stem cells, and bone marrow-derived mononuclear cells, showed modest improvements in heart function. These benefits appeared to arise primarily through paracrine signaling, rather than direct tissue regeneration. More recently, researchers have focused on extracellular vesicles and exosomes, acellular messengers that deliver molecular signals to encourage new blood vessel growth, reduce inflammation, and promote cell survival. Breakthroughs in direct cardiac reprogramming now make it possible to convert fibroblasts into cardiomyocyte-like cells, while induced pluripotent stem cell-derived cardiomyocytes open new doors for personalized disease modeling and potential myocardial reconstruction. Advances in gene editing, most notably clustered regularly interspaced short palindromic repeats/Cas9, are elevating the precision and efficiency of regenerative interventions. Finally, synthetic biology and tissue engineering innovations are accelerating the development of physiological cardiac tissue patches and driving the aspiration of a fully implantable bioartificial heart. These multidisciplinary innovations are redefining the boundaries of cardiac care and bringing the prospect of myocardial regeneration increasingly within reach.

PMID:40530862 | DOI:10.1097/CRD.0000000000000972

Categorías: Terapia celular

Cardiac Regeneration and Repair in Zebrafish and Mammalian Models

Mar, 06/17/2025 - 10:00

Curr Cardiol Rep. 2025 Jun 17;27(1):95. doi: 10.1007/s11886-025-02235-6.

ABSTRACT

AIM: In this review, we discuss the regenerative processes in the heart, focusing on non-cardiomyocyte cell populations (fibroblasts, immune cells, and endothelial cells) in zebrafish and mammals. We highlight the role of signaling pathways in heart repair and the potential for therapeutic strategies based on these mechanisms.

PURPOSE OF REVIEW: The review examines key molecular and cellular mechanisms in cardiac regeneration, with a focus on fibroblasts, immune modulation, and endothelial function, to identify strategies for enhancing heart repair.

RECENT FINDINGS: Recent advancements in characterization of different cell types at the single cell level, along with the discovery of regeneration enhancer elements, have opened new avenues for cardiac regeneration. Targeting the epicardium, along with fibroblast activation, immune modulation, and endothelial signaling, may offer therapeutic strategies to enhance heart regeneration by supporting cardiomyocytes in mice and humans. While non-cardiomyocytes in zebrafish contribute to heart regeneration, in mice and humans, these cells often drive fibrosis instead. Understanding these species-specific differences is crucial for optimizing therapeutic approaches to treat cardiac injury and prevent fibrosis.

PMID:40527972 | PMC:PMC12174244 | DOI:10.1007/s11886-025-02235-6

Categorías: Terapia celular

Extracellular Vesicle-Enhanced Stem Cell Therapy in Acute Myocardial Infarction: A Case Report of Cardiac Regeneration from a Bypass Surgery

Jue, 06/12/2025 - 10:00

Stem Cell Rev Rep. 2025 Jun 12. doi: 10.1007/s12015-025-10910-y. Online ahead of print.

ABSTRACT

Myocardial infarction is still a significant cause of morbidity and mortality. Coronary artery obstruction reduces blood flow and oxygen supply to the heart muscle, resulting in ischemia and necrosis. Due to the heart's limited healing mechanisms, regenerative therapies to restore cardiac function are being investigated. This case report, describes the utilization of mesenchymal stem cells and extracellular vesicles derived from these cells during coronary artery bypass grafting surgery for the patient who had a recent acute myocardial infarction. A direct injection into the myocardium was performed during surgery after a failed percutaneous coronary intervention. During the follow-up, the patient demonstrated improvements in cardiac function, with the ejection fraction increasing from 28 to 35% as measured by myocardial perfusion scintigraphy, and up to 43% on echocardiographic assessment at six months post-operation, as well as decreases in end-diastolic and end-systolic volumes. Significantly, these advantages remained despite the blockage of the bypass graft. The present case shows that extracellular vesicle-enhanced stem cell treatment may be used in surgical revascularization to restore myocardium in severe ischemic damage.

PMID:40504481 | DOI:10.1007/s12015-025-10910-y

Categorías: Terapia celular

Pericardial Administration of Extracellular Vesicles Derived from Bone Marrow Stem Cells Improved Doxorubicin-induced Heart Failure with Mid Range Ejection Fraction (HFmrEF) in Rats

Mié, 06/11/2025 - 10:00

Cardiovasc Drugs Ther. 2025 Jun 11. doi: 10.1007/s10557-025-07721-1. Online ahead of print.

ABSTRACT

PURPOSE: This study investigates the therapeutic effects of extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (BMSCs) on heart failure in rats through intrapericardial injection.

METHODS: Initially, doxorubicin was used to induce apoptosis in H9C2 cells, and the protective effects of EVs on these cells were evaluated. EVs were injected into the pericardial cavity of rats with heart failure, followed by real-time in vivo imaging and immunofluorescence detection to confirm the implantation of EVs in the myocardium. Cardiac function was assessed via echocardiography after the pericardial injection. Immunohistochemical techniques were employed to measure the expression of BNP, IL-6, CD31, and VEGFA in rat heart tissue. Additionally, the collagen fiber content in the heart tissue was detected using Masson staining.

RESULTS: The results showed that EVs derived from BMSCs at a concentration of 100 μg/ml most effectively promoted the proliferation of H9C2 cells and protected them from doxorubicin-induced damage. Compared to the heart failure group, EV treatment significantly increased LVEF, LVFS, and CO. Following intrapericardial injection of BMSCs, in vivo imaging revealed high-intensity fluorescence signals in the cardiac region, and immunofluorescence confirmed the implantation of EVs in the myocardium. Post-EV treatment, the expression levels of BNP and IL-6 and collagen content in myocardial tissue were significantly reduced, whereas the levels of CD31 and VEGFA were significantly increased.

CONCLUSION: EVs derived from BMSCs, when injected into the pericardial cavity, significantly improved cardiac function in heart failure rats through anti-inflammatory and pro-angiogenic mechanisms.

PMID:40498225 | DOI:10.1007/s10557-025-07721-1

Categorías: Terapia celular

Exploring hiPSC-CM replacement therapy in ischemic hearts

Mar, 06/10/2025 - 10:00

Basic Res Cardiol. 2025 Jun 10. doi: 10.1007/s00395-025-01117-w. Online ahead of print.

ABSTRACT

Ischemic heart disease is one of the leading causes of heart failure and death worldwide. The loss of cardiomyocytes following a myocardial infarction drives the remodeling process, which, in most cases, ultimately leads to heart failure. Since the available treatment options only slow down the remodeling process without tackling the causes of heart failure onset (i.e., cardiomyocyte loss and inability of the remaining cardiomyocytes to enter the cell cycle and regenerate the heart), in the last two decades, cardiovascular research focused on finding alternative solutions to regenerate the heart. So far, the investigated approaches include a variety of methods aiming at manipulation of non-coding RNAs, such as long non-coding RNA (lncRNA), circular RNA (circRNA), and microRNA (miRNA), and growth factors to enable the cardiomyocytes to re-enter the cell cycle, direct reprogramming of fibroblasts into cardiomyocytes (CM), and CM replacement therapy, all of them with the main goal to replace the loss of cardiomyocytes and restore the heart function. The development of reprogramming protocols from somatic cells to induced pluripotent stem cells (iPSCs) by Yamanaka and Takahashi, along with advancements in differentiation protocols to generate almost pure populations of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), has fostered optimism in cardiac regenerative medicine. Despite these advancements, critical concerns arose regarding the survival and retention of the engrafted cells, arrhythmogenicity, and immune response. Over time, much effort has been put into enhancing iPSC-CM therapy with different methods, ranging from anti-apoptotic small molecule-based approaches to tissue engineering. In this review, we discuss the evolution of cardiac cell therapy, highlighting recent advancements and the remaining challenges that must be overcome to translate this promising approach into clinical practice.

PMID:40493218 | DOI:10.1007/s00395-025-01117-w

Categorías: Terapia celular

Leveraging electric current stimulation and chemical induction to enhance MSC differentiation into cardiomyocytes

Vie, 06/06/2025 - 10:00

Regen Med. 2025 May;20(5):181-192. doi: 10.1080/17460751.2025.2514905. Epub 2025 Jun 6.

ABSTRACT

AIMS: To investigate whether direct electric current stimulation, when combined with chemical induction, can enhance the cardiomyogenic differentiation of mesenchymal stem cells (MSCs), offering a potential strategy for cardiac regeneration.

MATERIALS & METHODS: Bone marrow-derived MSCs were subjected to short-term microcurrent stimulation (90 seconds) using an electroporation cuvette with voltages of 1-10 V and pulse parameters of 2 ms at 0.5-2 hz. 5-azacytidine (5-aza) was added as a chemical inducer. In vitro analyses included morphological observation, immunofluorescence staining, qPCR, and flow cytometry. In vivo, pretreated MSCs were injected into a rat myocardial infarction model.

RESULTS: Electrical stimulation enhanced MSC alignment and upregulated cardiomyocyte-specific markers. Gene and protein expression analyses confirmed enhanced differentiation, especially in the combined treatment group. In vivo transplantation resulted in partial restoration of myocardial architecture, though no significant ventricular wall thickening was observed within four weeks.

CONCLUSIONS: This study introduces a dual approach combining electrical and chemical cues to promote cardiomyogenic differentiation in MSCs. The use of a simple electroporation cuvette offers a practical and accessible method, with potential translational relevance for future cardiac repair strategies.

PMID:40476836 | DOI:10.1080/17460751.2025.2514905

Categorías: Terapia celular

Ultrasound-triggered targeted delivery of engineered ADSCs-derived exosomes with high SDF-1alpha levels to promote cardiac repair following myocardial infarction

Mar, 06/03/2025 - 10:00

Int J Pharm. 2025 Jun 1;681:125786. doi: 10.1016/j.ijpharm.2025.125786. Online ahead of print.

ABSTRACT

Myocardial Infarction (MI) is still a leading cause of mortality, and current treatments primarily focus on symptom alleviation and blood flow restoration, with limited capacity for myocardial repair. Exosomes, key mediators of intercellular communication, have demonstrated potential to promote myocardial regeneration but exhibit limited cardiac-targeting efficiency due to rapid accumulation in other organs. To overcome this limitation, we designed targeted nanobubbles (TNBCD81-cRGD) loaded with exosomes derived from adipose-derived stem cells (ADSCs) in this study. These ADSCs were genetically modified through viral transfection to secrete exosomes with high expression of stromal cell-derived factor 1α (SDF-1α), which was upregulated in the infarcted region and promotes stem cell homing via the SDF-1α-CXCR4 axis. The nanobubbles, modified with anti-CD81 antibodies and cRGD, enabled efficient targeting of ischemic myocardium under Low-Intensity Pulsed Ultrasound (LIPUS) irradiation. Our study demonstrated that the combination of targeted nanobubbles, ADSC-derived exosomes with high SDF-1α expression, and LIPUS irradiation enhanced exosome retention in the heart, improved therapeutic efficacy, and promoted myocardial repair. This approach holds potential for advancing exosome-based therapies in myocardial infarction treatment.

PMID:40460966 | DOI:10.1016/j.ijpharm.2025.125786

Categorías: Terapia celular

Neural Organoids Protect Engineered Heart Tissues From Glucolipotoxicity by Transferring Versican in a Co-Culture System

Mar, 06/03/2025 - 10:00

Cell Prolif. 2025 Jun 3:e70070. doi: 10.1111/cpr.70070. Online ahead of print.

ABSTRACT

Metabolic disorders could cause dysregulated glucose and lipid at the systemic level, but how inter-tissue/organ communications contribute to glucolipotoxicity is difficult to dissect in animal models. To solve this problem, myocardium and nerve tissues were modelled by 3D engineered heart tissues (EHTs) and neural organoids (NOs), which were co-cultured in a generalised medium with normal or elevated glucose/fatty acid contents. Morphology, gene expression, cell death and functional assessments detected no apparent alterations of EHTs and NOs in co-culture under normal conditions. By contrast, NOs significantly ameliorated glucolipotoxicity in EHTs. Transcriptomic and protein secretion assays identified the extracellular matrix protein versican as a key molecule that was transferred from NOs into EHTs in the high-glucose/fatty acid condition. Recombinant versican protein treatment was sufficient to reduce glucolipotoxicity in EHTs. Adeno-associated virus-delivered versican overexpression was sufficient to ameliorate cardiac dysfunction in a murine model of diabetic cardiomyopathy. These data provide the proof-of-concept evidence that inter-tissue/organ communications exist in the co-culture of engineered tissues and organoids, which could be systemically studied to explore potential pathological mechanisms and therapeutic strategies for multi-organ diseases in vitro.

PMID:40459298 | DOI:10.1111/cpr.70070

Categorías: Terapia celular

Human induced pluripotent stem cell derived nanovesicles for cardiomyocyte protection and proliferation

Lun, 06/02/2025 - 10:00

Bioact Mater. 2025 May 2;50:585-602. doi: 10.1016/j.bioactmat.2025.04.017. eCollection 2025 Aug.

ABSTRACT

It remains a significant challenge to reactivate the cell cycle activity of adult mammalian cardiomyocytes (CMs). This study created a hypo-immunogenic human induced pluripotent stem cell (hiPSC) line using clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 gene editing to knockout β2-microglobulin in hiPSCs (B2MKOhiPSCs) for manufacturing nanovesicles (B2MKOhiPSC-NVs). Approximately 9500 B2MKOhiPSC-NVs were produced from a single B2MKOhiPSC. Proteomic analyses indicated that, compared to B2MKOhiPSCs, the cargos of B2MKOhiPSC-NVs were enriched in spindle and chromosomal proteins, as well as proteins that regulate the cell cycle and scavenge reactive oxygen species (ROS). When administrated to hiPSCs derived CMs (hiPSC-CMs), B2MKOhiPSC-NVs reduced lactate dehydrogenase leakage and apoptosis in hypoxia-cultured hiPSC-CMs through activating the AKT pathway, protected hiPSC-CMs from H2O2-induced damage by ROS scavengers in the NV cargo, increased hiPSC-CM proliferation via the YAP pathway, and were hypoimmunogenic when co-cultured with human CD8+ T cells or delivered to mice. Furthermore, when B2MKOhiPSC-NVs or 0.9 % NaCl were intramyocardially injected into mice after cardiac ischemia/reperfusion injury, cardiac function and infarct size, assessed 4 weeks later, were significantly improved in the B2MKOhiPSC-NV group, with increased mouse CM survival and cell cycle activity. Thus, the proteins in the B2MKOhiPSC-NV cargos convergently activated the AKT pathway, scavenged ROS to protect CMs, and upregulated YAP signaling to induce CM cell cycle activity. Thus, B2MKOhiPSC-NVs hold great potential for cardiac protection and regeneration.

PMID:40453695 | PMC:PMC12124652 | DOI:10.1016/j.bioactmat.2025.04.017

Categorías: Terapia celular

An overview on cardiac regeneration revolution: exploring the promise of stem cell therapies

Mié, 05/28/2025 - 10:00

Mol Biol Rep. 2025 May 28;52(1):511. doi: 10.1007/s11033-025-10580-6.

ABSTRACT

Cardiovascular diseases (CVDs) remain the leading cause of global mortality, with myocardial infarction (MI) and subsequent heart failure (HF) posing significant clinical challenges. Despite advancements in pharmacological and surgical interventions, the limited regenerative capacity of the adult human heart necessitates innovative therapeutic strategies. Stem cell-based therapies have emerged as a promising approach to cardiac regeneration, aiming to restore damaged myocardial tissue through cell replacement and paracrine-mediated repair mechanisms. This review provides a comprehensive overview of the current landscape of stem cell therapies for cardiac regeneration, focusing on the molecular mechanisms, cell types, delivery techniques, and recent clinical advancements. We highlight the roles of key signaling pathways, including NOTCH, PI3K/Akt, Wnt/β-catenin, Hippo/YAP, and MAPK, in regulating cardiomyocyte proliferation, angiogenesis, fibrosis, and inflammation. Additionally, we discuss the therapeutic potential of various stem cell types, such as mesenchymal stem cells (MSCs), cardiac progenitor cells (CPCs), induced pluripotent stem cells (iPSCs), and embryonic stem cells (ESCs), in promoting cardiac repair. Despite promising preclinical results, challenges such as low cell retention, immune rejection, and inconsistent clinical outcomes persist. Recent advancements in genetic engineering, and innovative delivery methods, including transendocardial and intracoronary injections, offer new avenues for enhancing therapeutic efficacy. This review underscores the need for further research to optimize stem cell-based therapies, improve clinical trial design, and translate these innovative approaches into effective treatments for heart disease. By addressing these challenges, stem cell therapy holds the potential to revolutionize cardiac regeneration and improve outcomes for patients with ischemic heart disease and heart failure.

PMID:40434692 | DOI:10.1007/s11033-025-10580-6

Categorías: Terapia celular

Identification of Critical Molecular Pathways Induced by HDAC11 Overexpression in Cardiac Mesenchymal Stem Cells

Mié, 05/28/2025 - 10:00

Biomolecules. 2025 May 3;15(5):662. doi: 10.3390/biom15050662.

ABSTRACT

HDAC11, the only class IV histone deacetylase, primarily functions as a fatty acid deacylase and has been implicated in metabolic regulation, cancer stemness, and muscle regeneration. However, its role in cardiac mesenchymal stem cells (CMSCs) remains unexplored. To investigate the effects of HDAC11 overexpression on the gene regulatory networks in CMSCs, we treated mouse CMSCs with an adenoviral vector encoding human HDAC11 (Ad-HDAC11) versus adenoviral GFP (Ad-GFP) as a control. Gene expression and pathway enrichment were assessed using RNA sequencing (RNA-seq), and HDAC11 overexpression was validated at the RNA and protein levels through qRT-PCR and Western blot. RNA-seq and Gene Ontology (GO) analysis revealed that HDAC11 overexpression activated cell cycle pathways while suppressing nucleotide transport and phagolysosome-related processes. Furthermore, pHH3 protein level was increased, suggested enhanced proliferation in HDAC11-overexpressed CMSCs. qRT-PCR also confirmed the downregulation of GM11266, a long non-coding RNA, in HDAC11-overexpressing CMSCs. In summary, HDAC11 overexpression promotes transcriptional reprogramming, cell cycle progression, and CMSC proliferation, underscoring its potential role in regulating CMSC growth and division.

PMID:40427555 | PMC:PMC12109384 | DOI:10.3390/biom15050662

Categorías: Terapia celular

Stem Cell Therapy for Myocardial Infarction Recovery: Advances, Challenges, and Future Directions

Mié, 05/28/2025 - 10:00

Biomedicines. 2025 May 16;13(5):1209. doi: 10.3390/biomedicines13051209.

ABSTRACT

Myocardial infarction (MI) is a leading cause of morbidity worldwide, resulting from ischemic damage and necrosis to cardiomyocytes. While the standard treatment regimen for MI can be successful in restoring coronary perfusion, it typically does not resolve myocardial damage, which can leave patients particularly vulnerable to complications such as heart failure or electrical conduction abnormalities. Stem cell therapies offer a promising novel approach aimed at restoring cardiac function and decreasing the incidence of functional complications after an MI. This review used a literature search to evaluate the current landscape of stem cell therapy for post-MI recovery and focuses on the stem cell candidates for MI recovery therapy, delivery methods of such treatment, and their effectiveness. Both preclinical and clinical trials have demonstrated the safety of stem cells, but have struggled with limited cell retention, inconsistent efficacy, and survival. Mechanisms are employed by stem cells to promote regeneration, such as paracrine signaling, angiogenesis, and structural remodeling, in addition to the various stem cell delivery methods, including intracoronary infusion, direct myocardial injection, and intravenous administration. Furthermore, some strategies to combat past challenges in this field are discussed; for instance, extracellular vesicles, bioengineered patches, hydrogels, gene editing, and bioprinting. This article will provide a framework for future research in stem cell therapies and highlight the current progress in the field.

PMID:40427036 | PMC:PMC12109359 | DOI:10.3390/biomedicines13051209

Categorías: Terapia celular

Injectable Stem Cell-Based Therapies for Myocardial Regeneration: A Review of the Literature

Mar, 05/27/2025 - 10:00

J Funct Biomater. 2025 Apr 23;16(5):152. doi: 10.3390/jfb16050152.

ABSTRACT

Stem cell-based therapies are an emerging treatment modality aimed at replenishing lost cardiomyocytes and improving myocardial function after cardiac injury. This review examines the current state of research on injectable stem cell therapies in the setting of cardiovascular disease given their relative simplicity and ability for deep myocardial tissue penetration. Various methods of cell delivery, ranging in level of invasiveness and procedural complexity, have been developed, and numerous cell types have been studied as potential sources of stem cells, each with distinct advantages and disadvantages. We discuss key challenges associated with this approach, including low stem cell retention after transplantation and the innovative biomolecular strategies that have been explored to address this issue. Overall, investigations into the application of stem cells toward cardiac regeneration remain predominantly in the preclinical stage with a number of small, early-phase clinical trials. However, continued scientific advancements in stem cell technology may provide transformative treatment options for patients with heart failure, offering improved survival and quality of life.

PMID:40422817 | PMC:PMC12111900 | DOI:10.3390/jfb16050152

Categorías: Terapia celular

Pluripotent stem cell-derived cardiomyocyte transplantation: marching from bench to bedside

Lun, 05/26/2025 - 10:00

Sci China Life Sci. 2025 May 23. doi: 10.1007/s11427-024-2801-x. Online ahead of print.

ABSTRACT

Cardiovascular diseases such as myocardial infarction, heart failure, and cardiomyopathy, persist as a leading global cause of death. Current treatment options have inherent limitations, particularly in terms of cardiac regeneration due to the limited regenerative capacity of adult human hearts. The transplantation of pluripotent stem cell-derived cardiomyocytes (PSC-CMs) has emerged as a promising and potential solution to address this challenge. This review aims to summarize the latest advancements and prospects of PSC-CM transplantation (PCT), along with the existing constraints, such as immune rejection and engraftment arrhythmias, and corresponding solutions. Encompassing a comprehensive range from fundamental research findings and preclinical experiments to ongoing clinical trials, we hope to offer insights into PCT from bench to bedside.

PMID:40418524 | DOI:10.1007/s11427-024-2801-x

Categorías: Terapia celular

In vivo assessment of iPSC-cardiomyocyte loaded auxetic cardiac patches following chronic myocardial infarction

Vie, 05/23/2025 - 10:00

Biomaterials. 2025 Dec;323:123418. doi: 10.1016/j.biomaterials.2025.123418. Epub 2025 May 20.

ABSTRACT

Novel cardiac patch designs achieved by advanced 3D manufacturing continue to have favorable impacts on the repair and regeneration of the myocardium after injury. Briefly, auxetic units with a negative Poisson's ratio have already shown remarkable promise for serving as a next-generation complex scaffold in left ventricular disease. In this study we biofabricated a 3D printed polycaprolactone (PCL) cardiac auxetic patch loaded with high density contractile induced pluripotent stem cell-derived cardiomyocytes (iCMs) and examined the synergist effect of iCM auxetic patches on a chronic myocardial infarct rodent model compared to a stiffer non-auxetic control patch architecture. A week after the induction of a temporary left anterior descending artery ligation, we administered the treatment groups in the form of patch implantation over the ischemic area after initial acute inflammation was complete and prior to granulation tissue formation following the infarct for clinical relevance. Our findings highlight that auxetic patches can provide additional ventricular support and diminished adverse ventricular remodeling, as seen through ejection fraction outputs and histology, and iCM-laden auxetics show localized regenerative potential through increased vascularization compared to controls with no patch or a non-auxetic patch architecture. Exploration on the impact of a negative Poisson's ratio on both global functional outcomes and local therapeutic benefit highlights that iCM-laden auxetics should be further surveyed for other cardiac pathophysiologic conditions, including more in-depth studies on infarction or right ventricular disease.

PMID:40408975 | DOI:10.1016/j.biomaterials.2025.123418

Categorías: Terapia celular

PTMA controls cardiomyocyte proliferation and cardiac repair by enhancing STAT3 acetylation

Vie, 05/23/2025 - 10:00

Sci Adv. 2025 May 23;11(21):eadt9446. doi: 10.1126/sciadv.adt9446. Epub 2025 May 23.

ABSTRACT

The adult mammalian heart has limited regenerative capacity due to the low proliferative ability of cardiomyocytes, whereas embryonic cardiomyocytes exhibit robust proliferative potential. Using single-cell RNA sequencing of embryonic hearts, we identified prothymosin α (PTMA) as a key factor driving cardiomyocyte proliferation. Overexpression of PTMA in primary mouse and rat cardiomyocytes significantly promoted cardiomyocyte proliferation and similarly enhanced proliferation in human iPSC-derived cardiomyocytes. Conditional knockout of Ptma in cardiomyocytes impaired neonatal heart regeneration. AAV9-mediated overexpression of Ptma extended the neonatal proliferative window and showed therapeutic promise for enhancing adult heart regeneration. Mechanistically, PTMA interacted with MBD3, inhibiting its deacetylation activity within the MBD3/HDAC1 NuRD complex. This inhibition increased STAT3 acetylation, which positively regulated STAT3 phosphorylation and activation of its target genes. These findings establish PTMA as a critical regulator of heart regeneration and suggest its potential as a therapeutic target for ischemic myocardial injury.

PMID:40408476 | PMC:PMC12101487 | DOI:10.1126/sciadv.adt9446

Categorías: Terapia celular

Therapeutic Performance of Hydrogel-Derived Extracellular Wharton's Jelly Matrix and Wharton's Jelly Mesenchymal Stem Cells in Repairing Infarcted Myocardium of Ischemic Rats: a Preclinical Study

Mar, 05/20/2025 - 10:00

Macromol Biosci. 2025 May 20:e70007. doi: 10.1002/mabi.202400578. Online ahead of print.

ABSTRACT

Following myocardial infarction (MI), progressive death of cardiomyocytes and subsequent loss of the extracellular matrix leads to drastic alterations in the structure and mechanical performance of the heart, thereby leading to infarct expansion and cardiac dysfunction. To compensate for the lack of reparative potency in infarcted hearts and to inhibit negative remodeling in the myocardium after MI, stem cell-based therapy in combination with hydrogels has emerged as a promising strategy to improve cardiac function recovery. In this study, a novel injectable hydrogel derived from decellularized Wharton's jelly extracellular matrix (DWJM) is prepared and examined the therapeutic performance of a combination of bioactive DWJM hydrogels and Wharton's jelly mesenchymal stem cells (WJMSCs) for myocardial repair in ischemic rats. In vitro examinations indicated that the DWJM hydrogel exhibited appropriate rheological performance and is capable of undergoing sol-gel transition at 37 °C. After intramyocardial injection in MI rats, DWJM-trapped WJMSCs significantly improved cardiac function recovery, reduced scar formation, and promoted cardiomyogenesis and microvascular renewal compared to WJMSCs or DWJM hydrogels alone. The results demonstrated that the DWJM hydrogel and WJMSCs synergistically promoted myocardial repair, which further confirmed the promising stem cell therapy using the bioactive ECM hydrogel.

PMID:40391578 | DOI:10.1002/mabi.202400578

Categorías: Terapia celular