Therapeutic Efficacy of Cryopreserved, Allogeneic Extracellular Vesicles for Treatment of Acute Myocardial Infarction

Chung, Jennifer J.; Kim, Samuel T.; Zaman, Samir; Helmers, Mark R.; Arisi, Maria F.; Li, Elizabeth C.; Tran, Zoe; Chen, Carol W.; Altshuler, Peter J.; Chen, Minna; Burdick, Jason A.; Atluri, Pavan

doi:10.1536/ihj.20-224

Cited by 8 publications

(3 citation statements)

References 27 publications

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“…designed a HA/adamantane/β‐cyclodextrin shear‐thinning gel for local delivery of allogeneic endothelial stem cell‐derived sEVs. [ 138 ] This in vivo delivery vehicle improved contractility and scar thickness with minimal inflammatory and immune response.…”

Section: Cardiothoracic Surgery and Biomaterial‐assisted Sc‐sev Therapymentioning

confidence: 99%

Biomaterial‐Facilitated Local Delivery of Stem Cell‐Derived Small Extracellular Vesicles: Perspectives in Surgical Therapy

Tan,

Xu,

et al. 2024

Advanced Therapeutics

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Stem cell‐derived small extracellular vesicles that are either naturally produced or pharmacogenetically engineered have shown tremendous potential in regenerative medicine in recent years. These sEVs exert multiple therapeutic effects comparable or superior to their parental stem cells while avoiding the limitations of stem cell‐based therapy, such as infusion toxicity, immunogenicity, tumorigenic potential, and ethical issues. The two routine modalities of sEV administration are systemic injection and local delivery, each presenting distinct benefits and drawbacks. Various biomaterials have been developed to assist their local delivery to improve the targeting of organs, minimize non‐specific accumulation in vital organs, and ensure the protection and release of sEVs. Based on a thorough search and meticulous dissection of relevant literature from the past five years, we present this comprehensive, up‐to‐date, specialty‐specific, disease‐oriented, and preclinical review to expound on the surgical application and potential of stem cell‐derived sEVs. The local delivery of stem cell‐derived sEVs, which possess similar indications as systemic transfer, could treat numerous diseases encountered in orthopedic surgery, neurosurgery, plastic surgery, cardiothoracic surgery, general surgery, urology, otorhinolaryngology, ophthalmology, obstetrics and gynecology, and dental surgery. In addition, the biomaterials utilized encompass a wide range of sources (e.g., natural, synthetic, and hybrid polymers), format (e.g., scaffold, patch, spray, microneedle), and responsiveness (e.g., temperature, pH, and protein), which enables customized sEV therapy tailored to specific diseases. This review demonstrates biomaterial‐facilitated local delivery of stem cell‐derived sEVs as a viable alternative or even a superior option to systemic sEV therapy. Future collaboration among surgeons, biomaterial scientists, and stem cell researchers is essential to advance this research area.This article is protected by copyright. All rights reserved

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Section: Cardiothoracic Surgery and Biomaterial‐assisted Sc‐sev Therapymentioning

confidence: 99%

Biomaterial‐Facilitated Local Delivery of Stem Cell‐Derived Small Extracellular Vesicles: Perspectives in Surgical Therapy

Tan,

Xu,

et al. 2024

Advanced Therapeutics

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“…78c ( 10 ) is a potent inhibitor of CD38, however due to its molecular structure is insoluble in water, and is difficult to deliver orally or intravenously at large quantities. Targeted drug delivery using nano-particles or extracellular vesicles ( 114 ) to house CD38 inhibitors could overcome this difficultly and effectively deliver therapeutics to inhibit type III CD38. These solutions could be delivered during CPB as part of the cardioplegia solution, or as an aerosolized solution in the ventilator.…”

Section: Therapeutic Deliverymentioning

confidence: 99%

The role of CD38 in ischemia reperfusion injury in cardiopulmonary bypass and thoracic transplantation: a narrative review

Gouchoe,

Vijayakumar,

Aly

et al. 2023

J Thorac Dis

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Background and Objective Ischemia reperfusion injury (IRI) is often the underlying cause of endothelium breakdown and damage in cardiac or transplantation operations, which can lead to disastrous post-operative consequences. Recent studies of cluster of differentiation 38 (CD38) have identified its critical role in IRI. Our objective is to provide a comprehensive overview of CD38-mediated axis, pathways, and potential CD38 translational therapies for reducing inflammation associated with cardiopulmonary bypass (CPB) or thoracic transplantation and IRI. Methods We conducted a review of the literature by performing a search of the PubMed database on 2 April 2023. To find relevant publications on CD38, we utilized the MeSH terms: “CD38” AND “Ischemia” OR “CD38” AND “Transplant” OR “CD38” AND “Heart” from 1990–2023. Additional papers were included if they were felt to be relevant but were not captured in the MeSH terms. We found 160 papers that met this criterion, and following screening, exclusion and consensus a total of 36 papers were included. Key Content and Findings CD38 is most notably a nicotine adenine dinucleotide (NAD) + glycohydrolase (NADase), and a generator of Ca 2+ signaling secondary messengers. Ultimately, the release of these secondary messengers leads to the activation of important mediators of cellular death. In the heart and during thoracic transplantation, this pathway is intimately involved in a wide variety of injuries; namely the endothelium. In the heart, activation generally results in vasoconstriction, poor myocardial perfusion, and ultimately poor cardiac function. CD38 activation also prevents the accumulation of atherosclerotic disease. During transplantation, intracellular activation leads to infiltration of recipient innate immune cells, tissue edema, and ultimately primary graft dysfunction (PGD). Specifically, in heart transplantation, extracellular activation could be protective and improve allograft survival. Conclusions The knowledge gap in understanding the molecular basis of IRI has prevented further development of novel therapies and treatments. The possible interaction of CD38 with CD39 in the endothelium, and the modulation of the CD38 axis may be a pathway to improve cardiovascular outcomes, heart and lung donor organ quality, and overall longevity.

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“…The majority of published studies have used phosphate-buffered saline (PBS) and some have used sucrose and trehalose buffers ( Steffi et al, 2016 ; Busatto et al, 2018 ; Li et al, 2019 ). Preservation conditions need to be further optimized and validated in both in vitro and in vivo assays to ensure post-thaw potency of the EVs product is retained ( Chung et al, 2021 ). Alternatively, EV lyophilization has been successfully utilized to store EVs and may offer a simpler option for transport and storage ( Frank et al, 2018 ; Kusuma et al, 2018 ).…”

Section: Challenges In the Clinical Application Of Evsmentioning

confidence: 99%

From Mesenchymal Stromal Cells to Engineered Extracellular Vesicles: A New Therapeutic Paradigm

Johnson

Shojaee²,

Crow³

et al. 2021

Front. Cell Dev. Biol.

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Mesenchymal stromal cells (MSCs) are multipotent cells obtained from many tissues including bone marrow, adipose tissue, umbilical cord, amniotic fluid, and placenta. MSCs are the leading cell source for stem cell therapy due to their regenerative and immunomodulatory properties, their low risk of tumorigenesis and lack of ethical constraints. However, clinical applications of MSCs remain limited. MSC therapeutic development continues to pose challenges in terms of preparation, purity, consistency, efficiency, reproducibility, processing time and scalability. Additionally, there are issues with their poor engraftment and survival in sites of disease or damage that limit their capacity to directly replace damaged cells. A key recent development in MSC research, however, is the now widely accepted view that MSCs primarily exert therapeutic effects via paracrine factor secretion. One of the major paracrine effectors are extracellular vesicles (EVs). EVs represent a potential cell-free alternative to stem cell therapy but are also rapidly emerging as a novel therapeutic platform in their own right, particularly in the form of engineered EVs (EEVs) tailored to target a broad range of clinical indications. However, the development of EVs and EEVs for therapeutic application still faces a number of hurdles, including the establishment of a consistent, scalable cell source, and the development of robust GMP-compliant upstream and downstream manufacturing processes. In this review we will highlight the clinical challenges of MSC therapeutic development and discuss how EVs and EEVs can overcome the challenges faced in the clinical application of MSCs.

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Therapeutic Efficacy of Cryopreserved, Allogeneic Extracellular Vesicles for Treatment of Acute Myocardial Infarction

Cited by 8 publications

References 27 publications

Biomaterial‐Facilitated Local Delivery of Stem Cell‐Derived Small Extracellular Vesicles: Perspectives in Surgical Therapy

Biomaterial‐Facilitated Local Delivery of Stem Cell‐Derived Small Extracellular Vesicles: Perspectives in Surgical Therapy

The role of CD38 in ischemia reperfusion injury in cardiopulmonary bypass and thoracic transplantation: a narrative review

From Mesenchymal Stromal Cells to Engineered Extracellular Vesicles: A New Therapeutic Paradigm

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