Exosomes are extracellular vesicles released by many cell types with varying compositions. Major bioactive factors present in exosomes are protein, lipid, mRNA, and miRNA. Exosomes are fundamental regulators of cellular trafficking and signaling in both physiological and pathological conditions. Various conditions such as oxidative stress, endoplasmic reticulum stress, ribosomal stress, and thermal stress alter the concentration of exosomal mRNA, and miRNA, lipids, and proteins. Stem cell–derived exosomes have been shown to regulate a variety of stresses, either inhibiting or promoting cell balance. Stem cell–derived exosomes direct the crosstalk between various cell types which helps recovery by transferring information in proteins, lipids, and so on. This is one of the reasons why exosomes are used as biomarkers for a multitude of disease conditions. This review highlights the bioengineering of fabricated exosomal cargoes. It includes the manipulation and delivery of specific exosomal cargoes such as noncoding RNAs, recombinant proteins, immune modulators, therapeutic drugs, and small molecules. Such therapeutic approaches may precisely deliver the therapeutic drugs at the target site in the management of various disease conditions. Importantly, we have focused on the therapeutic applications of stem cell–derived exosomes in cardiovascular disease conditions such as myocardial infarction, ischemic heart disease, cardiomyopathy, heart failure, sepsis, and cardiac fibrosis. Generally, two approaches are being followed by researchers for exosomal bioengineering. This literature review will shed light on the role of stem cell–derived exosomes in stress balance and provides a new avenue for the treatment of cardiovascular diseases.

Introduction: Hutchinson-Gilford progeria (HGP) is a genetic disorder caused by a single nucleotide mutation in the Lamin A gene. This mutation causes the production of the abnormal lamin A protein called progerin. Children affected by this disorder age rapidly and die at an early age, mostly from cardiac pathologies. Another similar progeroid syndrome is Nestor-Guillermo progeria, in which the patients exhibit accelerated aging but have a longer life span. This latter syndrome is caused by a mutation that silences the BANF1 gene. Hypothesis: We hypothesize that BANF1 is linked to cardiovascular disease in Hutchinson-Gilford progeria patients. This gene could be targeted to reduce cardiac pathologies and increase the lifespan of patients with HGP. Methods: We obtained skin fibroblasts from two HGP patients and their respective parents from the Progeria Foundation. We successfully reprogrammed the fibroblasts into induced pluripotent stem cells by a safe non-viral method and further differentiated them into induced cardiomyocytes (iCMCs). Then, we performed multiple analyses to compare the iCMCs of the patients, their parents, and control iCMCs. Results: Through in-silico protein analysis, we were able to identify a relationship between nuclear lamina proteins and BANF1, which is also correlated to cardiac-specific proteins GATA4 and NKX2.5 ( Figure A ). Additionally, through qPCR ( Figure B ) and Western Blot ( Figure C ) analyses, we identified a significant difference in BANF1 expression between the progeria patient iCMCs and the other iCMCs. BANF1 was overexpressed in patient iCMCs, whereas, it had normal expression in patient fibroblasts when compared to control cells. Conclusions: We believe that BANF1 could be a good target for future therapeutic approaches to minimize cardiac pathologies in HGP patients and extend their lifespan.

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