bims-evecad 2026-05-31 papers

Issue of 2026–05–31
six papers selected by
Cliff Dominy

Cells. 2026 May 14. pii: 900. [Epub ahead of print]15(10):

Extracellular Vesicles in Cardiac Repair Approaches: Implications for In Vitro Heart Models and Potential ATMP Development.

Simona Di Stefani, Maura Cimino, Rosaria Tinnirello, Martina Maria Cocco, Cinzia Maria Chinnici, Giandomenico Amico, Valentina Di Felice, Filippo Macaluso, Bruno Douradinha, Paolo Di Nardo, Gioacchin Iannolo.

Cardiovascular diseases remain the leading cause of mortality in developed countries. Among these conditions, acute myocardial infarction (AMI) is associated with particularly high rates of cardiac morbidity and mortality. Cardiac development in mammals is primarily dependent on cardiomyocyte (CM) proliferation during embryonic and early postnatal stages. However, following birth, the proliferative capacity of CMs declines markedly, with only limited cellular renewal occurring during adult life in response to pathological injury. Consequently, the irreversible loss of functional cardiomyocytes and the subsequent formation of fibrotic scar tissue frequently lead to persistent cardiac dysfunction and progressive impairment of cardiac physiology. Cardiomyocyte self-renewal is a tightly regulated process involving multiple molecular pathways. Among factors implicated in this regulation, microRNAs (miRNAs) have emerged as key modulators coordinating both cardiac development and tissue repair mechanisms. In this context, extracellular vesicles (EVs) have attracted considerable interest as potential modulators of these regenerative processes. In particular, mesenchymal stromal cells (MSCs) represent a promising therapeutic platform due to their immunomodulatory and anti-fibrotic properties demonstrated across multiple in vitro and in vivo models. Furthermore, the therapeutic potential of MSC-derived EVs can be enhanced through bioengineering approaches aimed at improving targeted molecular delivery. In this review, we summarize recent advances in the development and application of EV-based therapeutic strategies, with particular emphasis on their potential use as advanced therapy medicinal products (ATMPs) for cardiovascular regeneration and repair.

Keywords: advanced therapy medicinal products (ATMPs); cardiac progenitor cells; cardiosphere-derived cells (CDCs); cardiospheres; heart transplantation; heart-on-a-chip technologies; mesenchymal stromal cells (MSCs); organ failure; organ-on-a-chip systems; organoids

DOI: https://doi.org/10.3390/cells15100900

Front Cardiovasc Med. 2026 ;13 1815938

The dual role of extracellular vesicles in vascular calcification: from molecular mechanisms to clinical translation.

Yuxia Zhang, Yujia Wang, Jian Lu, Xueqi Li, Zhiqing Chen, Xin Wang, Taotao Tang, Rining Tang.

Vascular calcification (VC) is an active and regulated pathological process, which plays a central role in cardiovascular disease. Extracellular vesicles (EVs) are now recognized as crucial players in this pathology. EVs are nanoscale membrane vesicles secreted by cells. According to their biogenesis, they are mainly divided into exosomes, microvesicles and apoptotic bodies. They are rich in proteins, nucleic acids, lipids and other biologically active molecules. EVs play a dual role in VC. Regarding the pro-calcific role, EVs released by vascular smooth muscle cells (VSMCs), endothelial cells (ECs), and macrophages drive the phenotypic transformation of VSMCs by serving as nucleation cores for hydroxyapatite crystal deposition and by delivering pro-inflammatory and osteogenic signaling molecules. In addition to local effects, EVs also mediate long-distance intercellular communication. Together, these actions establish and amplify a pro-calcific microenvironment. In the aspect of anti-calcification, protective EVs can antagonize the osteogenic signaling pathway and maintain vascular homeostasis by delivering inhibitory microRNA (miRNA) (such as miR-126-5p, miR-133) and proteins (such as matrix Gla protein). The progress of VC depends on the balance between pro-calcific and anti-calcific EVs. Given their central position in pathology, EVs have become a highly promising source of new biomarkers, therapeutic intervention targets and drug delivery carriers. This review systematically summarizes the basic biological characteristics of EVs and the specific mechanisms underlying their dual regulatory roles in VC. It also discusses the challenges and future prospects for their clinical translation, thereby highlighting current knowledge gaps and outlining the exploratory nature of diagnostic and therapeutic strategies against VC.

Keywords: anti-calcification; extracellular vesicles; pro-calcification; therapeutic target; vascular calcification

DOI: https://doi.org/10.3389/fcvm.2026.1815938

Biomark Res. 2026 May 29.

The actively secreted plasma extracellular vesicle troponin (ASPECT) study: circulating troponin in extracellular vesicles across cardiovascular disease cohorts.

Michail Spanos, Priyanka Gokulnath, Aarush Singh, Christopher Azzam, Ronak Wakhlu, Claire Lin, Ana-Chrysa Maravelias, Timothy Oasan, Albree Tower-Rader, Megan Wasfy, Petr Jarolim, James L Januzzi, Saumya Das.

Cardiac troponin is essential for diagnosing myocardial infarction, yet high-sensitivity assays frequently detect troponin elevations in non-ischemic contexts, complicating clinical decision-making. We investigated extracellular vesicle-associated (EV) versus non-vesicular (NEV) troponin in plasma samples from 266 participants across acute and chronic heart failure, type 1 and type 2 MI, hypertrophic cardiomyopathy, end-stage kidney disease, healthy individuals, and exercise states. EV troponin was negligible in necrosis-dominant conditions (MI, kidney disease) but constituted up to 40-60% of total troponin in chronic heart failure or hypertrophic cardiomyopathy; in healthy controls and athletes, troponin concentrations were near or below the detection limit, though detectable troponin was predominantly EV-associated. Unlike plasma troponin, EV troponin weakly correlated with natriuretic peptides or renal indices, suggesting a distinct release mechanism linked to chronic stress or physiological processes. These findings highlight the potential for EV troponin to distinguish active, non-necrotic processes from acute injury. Further study may clarify its prognostic utility and refine current diagnostics and risk stratification.

Keywords: Cardiac biomarkers; Cardiac troponin; Exosomes; Extracellular vesicles (EVs); Heart failure; Hypertrophic cardiomyopathy; Myocardial infarction

DOI: https://doi.org/10.1186/s40364-026-00947-7

Acta Pharmacol Sin. 2026 May 26.

The spleen-heart crosstalk in cardiovascular disease: integrating neural, immune, and secretory pathways.

Ke-Yu Liu, Yan-Fang Chen, Yue Luo, Liang-Qing Zhang, Wen-Liang Chen.

Emerging evidence links cardiovascular disease (CVD) to organ-to-organ signaling that extends beyond the heart. The spleen is increasingly recognized as an innervated immune organ that rapidly remodels after cardiovascular injury and, in turn, regulates myocardial inflammation, repair, and remodeling. Human studies support clinical relevance through associations between splenic imaging phenotypes and cardiovascular risk or prognosis, while animal studies provide mechanistic support through spleen-targeted perturbations and mapping of immune trafficking and secreted mediators. This review synthesizes spleen-heart crosstalk as three interacting, bidirectional pathways including neural, immune, and secretory, and highlights phase dependence and spleen-specific mechanisms. The neural pathway links cardiac stress sensing and central autonomic processing to splenic sympathetic signals; for example, transcutaneous auricular vagus nerve stimulation (taVNS) activates a vago-splenic axis that reduces infarct size in patients with acute myocardial infarction. The immune pathway involves splenic leukocyte reservoirs, extramedullary hematopoiesis, and trafficking programs that may initially exhibit inflammatory characteristics following injury but transition to reparative roles during the resolution phase. This is exemplified by CCR2-dependent splenic monocyte egress, which influences infarct inflammation, and CD169⁺Tim4⁺ splenic macrophages, which facilitate wound healing. The secretory pathway comprises soluble mediators and extracellular vesicles (EVs) signaling that can instruct splenic responses and modulate cardiac target cells; specific examples include placental growth factor (PlGF) release from the spleen driving adaptive remodeling in pressure overload, and VCAM-1⁺ endothelial cell-derived EVs rapidly mobilizing neutrophils to the ischemic myocardium. Despite these advancements, significant knowledge gaps remain: the precise identification of splenic cellular sources for soluble mediators and EVs, the determination of recipient cardiac cell types and their functional interactions, and the mapping of phase-specific neural circuit dynamics across various CVD states. Translational priorities include the implementation of time-windowed targeting informed by spleen-state biomarkers (e.g., splenic FDG-PET activity, volume/stiffness), rigorous source-to-target validation through lineage-restricted perturbations, and the development of recipient-level engagement panels to facilitate mechanism-based, spleen-informed therapies for CVD.

Keywords: cardiovascular disease; extracellular vesicles; hematopoiesis; monocytes; neuroimmune; spleen

DOI: https://doi.org/10.1038/s41401-026-01841-6

Bioengineering (Basel). 2026 May 19. pii: 573. [Epub ahead of print]13(5):

Artificial Intelligence-Enabled Bioengineering of Extracellular Vesicle Platforms in Cardiovascular Medicine.

Nurittin Ardic, Rasit Dinc.

Extracellular vesicles (EVs) hold significant potential in cardiovascular diagnosis and treatment. However, their clinical applications are limited by challenges such as isolation efficiency, subpopulation heterogeneity, analytical standardization, and manufacturing scalability. Artificial intelligence (AI) and machine learning (ML) offer a computational framework to address these constraints through data-driven platform engineering. This review examines AI-assisted strategies in three interconnected EV platform pillars in cardiovascular medicine. These include: (i) isolation and processing platforms where ML algorithms optimize microfluidic separation and improve signal accuracy; (ii) analytical and diagnostic platforms where deep learning supports single vesicle phenotyping, multi-omics biomarker engineering, and biosensor interpretation; and (iii) therapeutic and manufacturing platforms where AI guides cargo loading, biodistribution estimation, and process control. We also assess key translational challenges, including MISEV2023 compliance, dataset bias, reproducibility, and regulatory alignment. This review positions artificial intelligence as the fundamental layer of the EV bioengineering process, providing a structured framework for advancing EV-based cardiovascular platforms from laboratory research to clinical application.

Keywords: artificial intelligence; bioengineering; biosensors; extracellular vesicles; microfluidics; precision medicine

DOI: https://doi.org/10.3390/bioengineering13050573

Acta Pharm Sin B. 2026 May;16(5): 2838-2876

Extracellular vesicles: Revolutionizing targeted therapy for ischemic stroke.

Ju Bai, Jingshu Yang, Wei Liu, Bin Han, Shaoyan Jiang, Jinping Sun, Hongzhao Qi.

Ischemic stroke (IS) remains a leading cause of global death and disability, with treatment effectiveness limited by its complex mechanisms, which include blood-brain barrier (BBB) disruption, neuroinflammation, excitotoxicity, oxidative stress, and cell death. This review summarizes emerging research on extracellular vesicle (EV)-based therapies for IS. EVs, sourced from animals, plants, and microbes, have unique benefits as natural nanocarriers, such as inherent BBB permeability, biocompatibility, and the ability to deliver multiple therapeutic cargos (like miRNAs, proteins, and drugs). We evaluate how EVs target key IS issues: (1) restoring BBB integrity by stabilizing tight junctions (TJs) and reducing matrix metalloproteinases (MMPs), (2) modulating microglia to reduce neuroinflammation, (3) decreasing excitotoxicity, (4) scavenging reactive oxygen species (ROS) to lessen oxidative stress, and (5) inhibiting apoptosis, ferroptosis, and other cell death pathways. Additionally, engineered EVs, such as antibody-conjugated or magnetically guided types, exhibit improved targeting and treatment accuracy, yielding promising results. Despite significant preclinical promise, clinical application faces challenges in standardization, scalable production, and delivery improvement. EVs offer a transformative, multi-targeted approach with the potential to overcome current limitations in IS treatment.

Keywords: Blood–brain barrier; Extracellular vesicles; Functional recovery; Ischemic stroke; Neuroprotection; Oxidative stress; Pathomechanism; Targeted therapy

DOI: https://doi.org/10.1016/j.apsb.2026.03.025