bims-evecad 2026-02-01 papers

bims-evecad

Biomed News

on Extracellular vesicles and cardiovascular disease

Issue of 2026–02–01
six papers selected by
Cliff Dominy

Optimizing Extracellular Vesicles for Cardiac Repair Post-Myocardial Infarction: Approaches and Challenges.
Integrative Proteomics of Extracellular Vesicles from hiPSC-Derived Cardiac Organoids Reveals Heart Tissue-like Molecular Representativity.
Role of Extracellular Vesicles in Abdominal Aortic Aneurysm: Pathophysiology, Biomarkers, and Therapeutic Potentials.
Extracellular Vesicles as Biological Templates for Next-Generation Drug-Coated Cardiovascular Devices: Cellular Mechanisms of Vascular Healing, Inflammation, and Restenosis.
Bioengineered Cellular and Acellular Therapies for Ischemic Heart Disease in Clinically Relevant Models.
Exogenous dendritic cell-derived exosomes promote Treg differentiation via IDO1-Kyn-AhR axis and improve cardiac function after myocardial infarction.

Biomolecules. 2025 Dec 30. pii: 58. [Epub ahead of print]16(1):

Optimizing Extracellular Vesicles for Cardiac Repair Post-Myocardial Infarction: Approaches and Challenges.

Yanling Huang, Han Li, Jinjie Xiong, Xvehua Wang, Jiaxi Lv, Ni Xiong, Qianyi Liu, Lihui Yin, Zhaohui Wang, Yan Wang.

  Ischemic heart disease remains the leading cause of cardiovascular mortality worldwide. In myocardial infarction (MI), extracellular vesicles (EVs)-particularly small EVs (sEVs)-transport therapeutic cargo such as miR-21-5p, which suppresses apoptosis, and other proteins, lipids, and RNAs that can modulate cell death, inflammation, angiogenesis, and remodeling. This review synthesizes recent mechanistic and preclinical evidence on native and engineered EVs for post-MI repair, mapping therapeutic entry points across the MI timeline (acute injury, inflammation, and healing) and comparing EV sources (stem-cell and non-stem-cell), administration routes, and dosing strategies. We highlight engineering approaches-including surface ligands for cardiac homing, rational cargo loading to enhance potency, and biomaterial depots to prolong myocardial residence-that aim to improve tropism, durability, and efficacy. Manufacturing and analytical considerations are discussed in the context of contemporary guidance, with emphasis on identity, purity, and potency assays, as well as safety, immunogenicity, and pharmacology relevant to cardiac populations. Across small- and large-animal models, EV-based interventions have been associated with reduced infarct/scar burden, enhanced vascularization, and improved ventricular function, with representative preclinical studies reporting approximately 25-45% relative reductions in infarct size in rodent and porcine MI models, despite substantial heterogeneity in EV sources, formulations, and outcome reporting that limits cross-study comparability. We conclude that achieving clinical translation will require standardized cardiac-targeting strategies, validated good manufacturing practice (GMP)-compatible manufacturing platforms, and harmonized potency assays, alongside rigorous, head-to-head preclinical designs, to advance EV-based cardiorepair toward clinical testing.

Keywords:  EVs; cardiac repair; engineered exosomes; extracellular vesicles (EVs); ischemia–reperfusion (I/R) injury; myocardial infarction (MI); targeted delivery

DOI:  https://doi.org/10.3390/biom16010058
Int J Mol Sci. 2026 Jan 19. pii: 981. [Epub ahead of print]27(2):

Integrative Proteomics of Extracellular Vesicles from hiPSC-Derived Cardiac Organoids Reveals Heart Tissue-like Molecular Representativity.

Carlos Miguel Vital, José Manuel Inácio, Ana Sofia Carvalho, Hans Christian Beck, Rune Matthiesen, José António Belo.

  Cardiovascular diseases remain a growing concern worldwide. Hence, it is critical to understand cardiac development and disease in a relevant human-based in vitro model. Human cardiac organoids are an alternative approach to studying cardiogenesis, in the context of cell-cell communication, and disease etiology, using human induced pluripotent stem cells (hiPSCs). Extracellular vesicles (EVs) are nanosized particles harboring proteins, nucleic acids, and metabolites and are implicated in intercellular communication. Since cardiac development requires a complex interplay between several cell types, we hypothesize that EVs may mediate this communication. Here, we isolated EVs from hiPSC-derived cardiac organoids (cardEVs). LC-MS/MS was performed to analyze their protein cargo and compare it with those from a cardiomyocyte cell line (AC10 CM EVs) and from human heart explants of cadaveric donors (heEVs) using a bioinformatic approach. cardEVs share 48.9% of their proteins with heEVs, with important biological processes such as "Metabolism" and "Cardiac Function" highlighted in both proteomes. This overlap between the proteomes of cardEVs and heEVs suggests a molecular similarity between the two models. Therefore, we reiterate the importance of cardiac organoids as an excellent model for studying cardiac development and disease modeling, as well as to explore the complexity of intercellular communication.

Keywords:  cardiac development; cardiac organoids; disease modeling; extracellular vesicles; proteomics

DOI:  https://doi.org/10.3390/ijms27020981
Int J Mol Sci. 2026 Jan 06. pii: 567. [Epub ahead of print]27(2):

Role of Extracellular Vesicles in Abdominal Aortic Aneurysm: Pathophysiology, Biomarkers, and Therapeutic Potentials.

Kazuki Takahashi, Yusuke Yoshioka, Naoya Kuriyama, Shinsuke Kikuchi, Nobuyoshi Azuma, Takahiro Ochiya.

  Abdominal aortic aneurysm (AAA) is a life-threatening disease. Although AAA is generally asymptomatic, the mortality rate remains very high once rupture occurs, even with successful treatment. The pathophysiology of AAA involves inflammatory cell infiltration, smooth muscle cell apoptosis, and extracellular matrix degradation. However, there are various unclear aspects of pathophysiology due to cellular heterogeneity and multifactorial disease. Moreover, there are no blood biomarkers or available pharmacological drugs for AAA. Extracellular vesicles (EVs) are lipid bilayer particles released from every type of cell for intercellular communication. EVs include proteins, DNA, RNA (mRNA, microRNA), and lipids. EV cargos are delivered to recipient cells and modulate their biological effects. Although fewer studies have investigated EVs in AAA than in other cardiovascular diseases with similar molecular mechanisms, recent research indicates that EVs play a significant role in AAA development. Further research on EVs and AAA will contribute to the elucidation of AAA pathophysiology and the development of novel pharmacological drugs. In this review, we summarize the EV-associated pathophysiology, EV-based biomarkers, and EV-based treatment strategies in AAA. We also discuss the prospects for EVs research in AAA.

Keywords:  abdominal aortic aneurysm; biomarker; extracellular vesicles; microRNA

DOI:  https://doi.org/10.3390/ijms27020567
Cells. 2026 Jan 09. pii: 121. [Epub ahead of print]15(2):

Extracellular Vesicles as Biological Templates for Next-Generation Drug-Coated Cardiovascular Devices: Cellular Mechanisms of Vascular Healing, Inflammation, and Restenosis.

Rasit Dinc, Nurittin Ardic.

  While drug-eluting cardiovascular devices, including drug-eluting stents and drug-coated balloons, have significantly reduced restenosis rates, they remain limited by delayed vascular healing, chronic inflammation, and late adverse events. These limitations reflect a fundamental mismatch between current device pharmacology, which relies on nonselective antiproliferative drugs, and the highly coordinated, cell-specific programs that orchestrate vascular repair. Extracellular vesicles (EVs), nanometer-scale membrane-bound particles secreted by virtually all cell types, provide a biologically evolved platform for intercellular communication and cargo delivery. In the cardiovascular system, EVs regulate endothelial regeneration, smooth muscle cell phenotype, extracellular matrix remodeling, and macrophage polarization through precisely orchestrated combinations of miRNA, proteins, and lipids. Here, we synthesize mechanistic insights into EV biogenesis, cargo selection, recruitment, and functional effects in vascular healing and inflammation and translate these into a formal framework for EV-inspired device engineering. We discuss how EV-based or EV-mimetic coatings can be designed to sense the local microenvironment, deliver encoded biological "instruction sets," and function within ECM-mimetic scaffolds to couple local stent healing with systemic tissue repair. Finally, we outline the manufacturing, regulatory, and clinical trial issues that must be addressed for EV-inspired cardiovascular devices to transition from proof of concept to clinical reality. By shifting the focus from pharmacological suppression to biological regulation of healing, EV-based strategies offer a path to resolve the long-standing tradeoff between restenosis prevention and durable vascular healing.

Keywords:  biomimetic nanoparticles; cardiovascular devices; drug-eluting stents; endothelial cells; exosomes; extracellular vesicles; inflammation; restenosis; smooth muscle cells; vascular healing

DOI:  https://doi.org/10.3390/cells15020121
Bioengineering (Basel). 2026 Jan 12. pii: 81. [Epub ahead of print]13(1):

Bioengineered Cellular and Acellular Therapies for Ischemic Heart Disease in Clinically Relevant Models.

Kelsey C Muir, Clark Zheng, Keertana Yalamanchili, Riya Reddy, Alexander Joseph, Jad Hamze, Dwight D Harris, Frank W Sellke.

  Despite significant improvements in revascularization strategies and medical management, ischemic heart disease (IHD) remains the top cause of mortality and disability worldwide. The myocardium lacks regenerative capacity and consequently, recovery depends on re-establishing microvascular integrity and sustaining angiogenesis to preserve viable myocardium. Emerging and novel bioengineering approaches, such as stem cells, extracellular vesicles (EVs), and matrix-based strategies, seek to address this unmet need by promoting neovascularization and structural restoration. However, clinical translation remains limited by poor engraftment, product variability, and arrhythmogenic risk. Large animal models provide a clinically relevant platform to thoroughly investigate these interventions and ideally enhance their translational potential. This review discusses cellular approaches leveraging stem and progenitor cells and acellular modalities using extracellular vesicles, growth factors, or extracellular matrix-based scaffolds with an emphasis on large animal translational models and clinical trials.

Keywords:  angiogenesis; extracellular matrix; extracellular vesicles; ischemic heart disease; large animal models; regenerative therapy; stem cells

DOI:  https://doi.org/10.3390/bioengineering13010081
Int Immunopharmacol. 2026 Jan 24. pii: S1567-5769(26)00096-2. [Epub ahead of print]173 116253

Exogenous dendritic cell-derived exosomes promote Treg differentiation via IDO1-Kyn-AhR axis and improve cardiac function after myocardial infarction.

Yiran Qin, Youming Zhang, Mingxuan Li, Di Ding, Rong Luo, Haibo Liu.

  Regulatory T cells (Tregs) play a vital role in cardiac remodeling after myocardial infarction (MI). Our previous study demonstrated that dendritic cell-derived exosomes (DEXs) improve cardiac function after MI by promoting Treg differentiation. However, the underlying mechanisms remain incompletely understood. In this study, we found that necrotic HL-1 cardiomyocyte supernatant-conditioned DEXs (MI-DEXs) expressed high level of indoleamine 2,3-dioxygenase 1 (IDO1), which led to increased kynurenine (Kyn) production and subsequently upregulation of aryl hydrocarbon receptor (AhR) in CD4+ T cells. Overexpression of IDO1 in MI-DEXs enhanced Treg differentiation and further improved cardiac function after MI, whereas knockdown of IDO1 attenuated these effects. In addition, pharmacological inhibition of AhR abolished the enhanced Treg differentiation and functional benefits induced by IDO1-overexpressing MI-DEXs, both in vitro and in vivo. Collectively, our findings reveal a novel mechanism by which MI-DEXs promote Treg differentiation via the IDO1-Kyn-AhR axis, and suggest that administration of MI-DEXs could be a potential intervention to facilitate cardiac repair after MI.

Keywords:  Dendritic cells; Exosomes; Indoleamine 2,3-dioxygenase 1; Myocardial infarction; Regulatory T cells

DOI:  https://doi.org/10.1016/j.intimp.2026.116253