bims-evecad 2026-03-29 papers

Issue of 2026–03–29
three papers selected by
Cliff Dominy

Biomolecules. 2026 03 20. pii: 467. [Epub ahead of print]16(3):

Next-Generation Metabolic Reprogramming in iPSC-Derived Cardiomyocytes: CRISPR-EV Synergy for Precision Cardiac Regeneration.

Dhienda C Shahannaz, Tadahisa Sugiura.

Cardiovascular disease remains the leading global cause of mortality, largely due to the limited regenerative capacity of adult human myocardium. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) offer a scalable platform for cardiac repair and disease modeling; however, their persistent metabolic immaturity-characterized by reliance on glycolysis, reduced oxidative phosphorylation (OXPHOS), and structurally underdeveloped mitochondria-limits functional integration and long-term therapeutic efficacy. Recent advances indicate that targeted metabolic reprogramming can enhance mitochondrial biogenesis, increase ATP production, and improve stress resilience in iPSC-CMs. This review examines the complementary integration of CRISPR-based metabolic engineering and extracellular vesicle (EV)-mediated metabolic modulation as a systems-level strategy for cardiac maturation. We discuss CRISPR activation, interference, and epigenome-editing approaches targeting regulators such as PGC-1α, TFAM, and PPARs to promote stable enhancement of mitochondrial networks and respiratory capacity. In parallel, engineered EVs delivering miRNAs, metabolic enzymes, and redox modulators provide non-genomic mechanisms to optimize bioenergetic function and mitigate oxidative stress. By synthesizing mechanistic insights, quantitative bioenergetic metrics, and translational considerations, we propose CRISPR-EV synergy as a precision framework for durable metabolic maturation of iPSC-CMs, with implications for regenerative therapy, pharmacologic screening, and myocardial repair.

Keywords: CRISPR metabolic engineering; EV bioengineering; cardiac regeneration; cardiomyocyte maturation; extracellular vesicles; iPSC-derived cardiomyocytes; metabolic biomarkers; metabolic reprogramming; mitochondrial biogenesis; oxidative phosphorylation

DOI: https://doi.org/10.3390/biom16030467

Pharmaceutics. 2026 Mar 11. pii: 346. [Epub ahead of print]18(3):

Mechanistic Insights into the Cardioprotective Effects of Mesenchymal Stem Cell-Derived Exosomes in Myocardial Ischemic Injury: A Systematic Review.

Nur Athirah Othman Basri, Nur Aishah Che Roos, Amilia Aminuddin, Adila A Hamid, Chua Kien Hui, Mohd Kaisan Mahadi, Jaya Kumar, Azizah Ugusman.

Background: Myocardial ischemic injury, encompassing acute myocardial infarction (MI) and ischemia/reperfusion (I/R) injury, remains a major cause of cardiac morbidity and mortality worldwide, and is driven by interconnected molecular and cellular processes, including cardiomyocyte apoptosis, inflammatory activation, mitochondrial dysfunction, oxidative stress, and impaired angiogenesis. Mesenchymal stem cell (MSC)-derived exosomes have emerged as a promising cell-free nanotherapeutic strategy for cardiac repair due to their ability to transfer bioactive molecules that modulate multiple signaling networks involved in myocardial survival and regeneration. This systematic review aimed to synthesize evidence on the mechanistic basis of MSC-derived exosome mediated cardioprotection in myocardial ischemic injury. Methods: A systematic search of Ovid MEDLINE, Scopus, and Web of Science was conducted to identify studies investigating the effects of MSC-derived exosomes on myocardial ischemic injury. Eligible studies included clinical and preclinical models of MI or I/R injury assessing functional, biochemical, and molecular outcomes. Results: Seven preclinical studies published between 2015 and 2025 met the inclusion criteria. Exosome administration consistently improved cardiac function, reduced infarct size, and preserved myocardial architecture. Biochemical analyses revealed decreased cardiac injury markers, alongside suppressed apoptosis, inflammation, and oxidative stress. Mechanistically, MSC-derived exosomes delivered regulatory miRNAs (e.g., miR-19a, miR-125b, miR-205, miR-294) and lncRNAs (HAND2-AS1) that modulated key signaling pathways including PI3K/Akt, JAK2/STAT3, HAND2-AS1/miR-17-5p/Mfn2, and HIF-1α/VEGF. These molecular effects collectively inhibited apoptotic and inflammatory responses, enhanced mitochondrial integrity, and promoted angiogenesis and myocardial repair. Conclusions: MSC-derived exosomes confer robust cardioprotection against myocardial ischemic injury through integrated anti-apoptotic, anti-inflammatory, antioxidant, and pro-angiogenic mechanisms. Their multifaceted bioactivity, low immunogenicity, and potential for targeted delivery highlight their potential as a next-generation nanomedicine for ischemic heart disease. Future studies should emphasize standardized exosome production, mechanistic profiling, and translational validation in large-animal and clinical models.

Keywords: exosomes; extracellular vesicles; hypoxia/reoxygenation; ischemic heart disease; mesenchymal stem cells; myocardial ischemia/reperfusion injury

DOI: https://doi.org/10.3390/pharmaceutics18030346

Metabolites. 2026 Feb 24. pii: 148. [Epub ahead of print]16(3):

Tissue-Derived Small Extracellular Vesicles: Emerging Regulators of Inter-Organ Crosstalk in Health and Disease.

Yin-Qiong Huang, Chuan-Yu Zhong, George Burley, Yan-Chuan Shi, Shu Lin.

Small extracellular vesicles (sEVs; commonly referred to as "exosomes" in many studies) are nanoscopic messengers released by healthy and diseased cells that mediate intercellular communication by transferring proteins, lipids, and nucleic acids to local or distant recipient cells. In this narrative review, we synthesize recent evidence linking tissue-derived sEVs to neurological disorders (including neurodegeneration and traumatic brain injury), metabolic syndrome, cardiovascular diseases, cancers, and bone diseases, with a particular emphasis on CNS-periphery crosstalk across the blood-brain barrier. Compared with prior reviews that focus on single organ systems, we highlight cross-disease, cross-tissue mechanisms and summarize candidate biomarker cargos and therapeutic strategies in dedicated tables. While accumulating data support brain-body communication via sEVs, the concept of CNS-derived sEVs acting as a "third central efferent pathway" is presented here as an emerging hypothesis that complements-rather than replaces-neuronal and endocrine signaling. Overall, tissue-derived sEVs represent a promising but still evolving platform for diagnostic and therapeutic innovation, warranting standardized isolation/characterization and further clinical validation.

Keywords: biomarker; extracellular vesicles (EVs); inter-organ crosstalk; small extracellular vesicles (sEVs); therapeutic delivery

DOI: https://doi.org/10.3390/metabo16030148