Review: MSCs and Exosomes Production
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resources. Each method has its trade-offs; thus, a combination of techniques should be used to<br />
achieve the best results. Continuous advancements in EVs isolation technologies are expected<br />
to enhance the efficiency, yield, <strong>and</strong> purity of EVs preparations.<br />
Enhancing EVs <strong>Production</strong> from <strong>MSCs</strong><br />
Optimizing the production of EVs from <strong>MSCs</strong> can significantly lead to more effective application<br />
possibilities by ensuring that enough potent, high-quality EVs are available for research <strong>and</strong> clinical<br />
therapy.<br />
Currently, several strategies are being developed to boost EVs production:<br />
• Culturing with Bioactive Glass (BG) Ion Products: Culturing <strong>MSCs</strong> with BG ion productenriched<br />
medium significantly increases Extracellular Vesicles production without altering<br />
their inherent characteristics 5 .<br />
• Use of Small Molecules: Identified specific small molecules capable of enhancing<br />
Extracellular Vesicles production in <strong>MSCs</strong>, with ongoing research exploring their effects on<br />
the EVs composition <strong>and</strong> regenerative capacity 6 .<br />
• Preconditioning <strong>and</strong> Engineering: Innovative strategies such as preconditioning <strong>MSCs</strong> <strong>and</strong><br />
engineering EVs are being investigated to amplify the therapeutic activity of MSC-EVs 7 .<br />
Navigating the Evolving L<strong>and</strong>scape of Engineered EVs Therapies:<br />
Opportunity <strong>and</strong> Challenges in Clinical Translation<br />
The l<strong>and</strong>scape of EV-based therapies growing exponentially, with over 150 clinical trials,<br />
spanning various domains such as respiratory disorders, infectious diseases, <strong>and</strong> oncology 9 .<br />
Notably, MSC-EVs are particularly promising, offering a compelling alternative to traditional<br />
stem cell therapies. As we have talked earlier, MSC-EVs can replicate the therapeutic impacts<br />
of their source <strong>MSCs</strong>, with added benefits like reduced size, increased stability, <strong>and</strong> more<br />
versatile administration routes 10 . Various companies are at the forefront of advancing the<br />
therapeutic potential of EVs through the engineering of EVs membrane proteins. These<br />
developments have led to innovative treatments, such as the creation of inhalable COVID-19<br />
vaccines utilizing EVs derived from lung stem cells. The contributions from multiple<br />
companies have played a significant role in driving progress in this field. The exciting world<br />
of engineered Extracellular Vesicles therapy is on the brink of transforming how we approach<br />
healing, opening a whole new world of medical possibilities 11 . Despite the promise of MSC-<br />
EVs, challenges persist in translating these therapies from bench to bedside. Issues concerning<br />
safety, st<strong>and</strong>ardized isolation protocols, <strong>and</strong> EVs characterization require resolution 12 .<br />
Additionally, the heterogeneity of EVs populations, influenced by extracellular environmental<br />
factors, complicates their therapeutic application 13 . A deeper underst<strong>and</strong>ing of exosomal cargo<br />
<strong>and</strong> its disease-specific roles is imperative for the full realization of exosomal potential in<br />
clinical settings.<br />
Lastly, the scale-up of MSC-EVs production for clinical applications encounters significant<br />
difficulties, primarily due to the substantial volume required to treat a single patient. Traditional<br />
volume reduction methods, such as ultracentrifugation, are notably inefficient for this scale,<br />
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