A Minimally Invasive Exosome Spray Repairs Heart after Myocardial Infarction

Abstract

Myocardial infarction (MI) remains the most common cause of death worldwide. Many MI survivors will suffer from recurrent heart failure (HF), which has been recognized as a determinant of adverse prognosis. Despite the success of improved early survival after MI by primary percutaneous coronary intervention, HF after MI is becoming the major driver of late morbidity, mortality, and healthcare costs. The development of regenerative medicine has brought hope to MI treatment in the past decade. Mesenchymal stem cell (MSC)-derived exosomes have been established as an essential part of stem cell paracrine factors for heart regeneration. However, its regenerative power is hampered by low delivery efficiency to the heart. We designed, fabricated, and tested a minimally invasive exosome spray (EXOS) based on MSC exosomes and biomaterials. In a mouse model of acute myocardial infarction, EXOS improved cardiac function and reduced fibrosis, and promoted endogenous angiomyogenesis in the post-injury heart. We further tested the feasibility and safety of EXOS in a pig model. Our results indicate that EXOS is a promising strategy to deliver therapeutic exosomes for heart repair.

Extracellular Vesicles in Cardiovascular Diseases: Diagnosis and Therapy

“…EVs carried with miRNA-21 can effectively inhibit apoptosis and restore cardiac function in vivo and in vitro ( Song et al, 2019 ). The therapeutic benefits of EVs in CVDs have also been confirmed by large animal models such as pigs and nonhuman primates ( Li Q et al, 2021 ; Yao et al, 2021 ). The therapeutic effect of EVs has also been evaluated in several kinds of diseases through small animal models, including MI ( Couto et al, 2017 ), hindlimb ischemia ( Prabhu et al, 2017 ), and stroke ( Tian et al, 2018 ).…”

Development of Extracellular Vesicle Therapeutics: Challenges, Considerations, and Opportunities

“…Lungbased pathologies are employing inhalation as the method of administration to ensure site-specific delivery (NCT04389385, NCT04747574, and NCT04276987). Injections of EVs to sites of damage are another method of focusing delivery, with therapeutic application of EVs directly to arthritic joints Wu et al, 2019;Li et al, 2021b), venous ulcers (NCT04652531), inner ears (Gyorgy et al, 2017), eyes (NCT03437759), and heart [damaged myocardium (Yao J. et al, 2021)]. While suitable for individual treatments at injectionaccessible sites, ongoing release of EV-based therapeutics at inaccessible sites raises a challenge.…”

“…The injection or topical application of hydrogels and biogels offer a form of slowrelease EV administration directly to the site of injury (Li L. et al, 2020;Shi et al, 2021;Zhao et al, 2021;Zhu et al, 2021b). Furthermore, the recent development of EVcoated scaffolds, such as cardiac stents and cardiac fibrin patches, allow for the therapeutics extended release at the site of damage (Hu S. et al, 2021;Yao J. et al, 2021). As a minimally-invasive direct therapeutic delivery strategy, EVs have been shown to be released in high capacity in vivo from human stem cells within a semi-permeable chamber inserted subcutaneously for cardiac therapy (Kompa et al, 2021).…”

Engineering Injectable Anti‐Inflammatory Hydrogels to Treat Acute Myocardial Infarction

“…[ 193 ] In addition, Cheng et al designed a minimally invasive Exos spray based on MSC Exos and biomaterials to improve fibrosis after AMI. [ 194 ] In summary, the use of injectable hydrogels or myocardial patches to encapsulate MSCs or MSC‐derived EVs is an effective strategy for the treatment of AMI.…”