Mesenchymal stromal/stem cell (MSC)-derived exosomes in clinical trials

Abstract

Mesenchymal stromal/stem cells (MSCs) are widely utilized in cell therapy because of their robust immunomodulatory and regenerative properties. Their paracrine activity is one of the most important features that contribute to their efficacy. Recently, it has been demonstrated that the production of various factors via extracellular vesicles, especially exosomes, governs the principal efficacy of MSCs after infusion in experimental models. Compared to MSCs themselves, MSC-derived exosomes (MSC-Exos) have provided significant advantages by efficiently decreasing unfavorable adverse effects, such as infusion-related toxicities. MSC-Exos is becoming a promising cell-free therapeutic tool and an increasing number of clinical studies started to assess the therapeutic effect of MSC-Exos in different diseases. In this review, we summarized the ongoing and completed clinical studies using MSC-Exos for immunomodulation, regenerative medicine, gene delivery, and beyond. Additionally, we summarized MSC-Exos production methods utilized in these studies with an emphasis on MSCs source, MSC-Exos isolation methods, characterization, dosage, and route of administration. Lastly, we discussed the current challenges and future directions of exosome utilization in different clinical studies as a novel therapeutic strategy.

A Biomimetic Cardiac Fibrosis-on-a-Chip as a Visible Disease Model for Evaluating Mesenchymal Stem Cell-Derived Exosome Therapy

“…Having established a biomimetic cardiac fibrosis-on-a-chip, we next expected to utilize this chip for therapeutic exploration. Stem cell therapy has gained wide attention in the field of heart regeneration. ,, Particularly, MSC-Exo, which resolves intrinsic limitations of direct stem cell transplantation including immunogenicity and tumorigenesis risk, has been investigated for postmyocardial infarction healing. − Here we investigated whether MSC-Exo treatment could improve the TGF-β1-induced phenotype in our biomimetic chip. First, MSC-Exos were isolated by using a series of ultracentrifugations.…”

Cartilage stem/progenitor cells‐derived exosomes facilitate knee cartilage repair in a subacute osteoarthritis rat model

“…Recently, an increasing number of studies have shown that stem cell extracellular vesicles exhibit similar functions without these shortcomings 17,29 . Therefore, stem cell extracellular vesicle‐based therapy is of great importance in tissue engineering and translational medicine 30–32 …”

Persistent tailoring of MSC activation through genetic priming

“…HEK293T cells were obtained from ATCC (Manassas, VA) and maintained in the same media as the hTERT-MSCs between passage 2 and 30. The HEK cells were plated at 7.7E4 cells/cm 2 the day before transfection. For each transfection, 4.878μg of IRF1 lentiviral plasmid, 1.463μg of pMD2.G and 3.659μg of psPAX2 (Addgene, Watertown, MA) were transfected using JetPRIME (Polyplus, Illkirch, France).…”

“…Mesenchymal Stem/Stromal Cells (MSCs) are widely recognized for their potential for treating diverse classes of human diseases and disorders. 1 The efficacy of MSCs or their cell-free products 2,3 has been studied in hundreds of clinical trials 4 across multiple settings spanning neurodegenerative disorders, 5 inflammatory bowel disease, 6 cardiac diseases, 7 COVID-19, 8 and others. This broad potential stems from the ability of MSCs to simultaneously express and secrete a spectrum of different pleiotropic immunomodulatory and regenerative chemokines, cytokines, growth factors, metabolites, and vesicles.…”