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Box 4 Key questions about exosomes-based therapiesr

From: A review on exosomes application in clinical trials: perspective, questions, and challenges

Which cell sources are promising for the treatment of diseases? For example, whether MSCs-derived exosomes are useful for most diseases or not. In addition, exosomes may induce adverse outcomes and trigger malfunction, therefore, which source of MSCs are safe for exosomes purification?
Do other exosomes such as those of plant cells and bacteria have a superior advantage over animal ones?
Do pre-conditioning or modifying exosome-producing cells adversely affect the efficacy of exosomes? Because these modifications may induce unwanted alterations in exosomes, the effects and safety of modified exosomes should be assessed independently
What is the efficient isolation method to increase yield of exosomes?
Different methods such as ultrafiltration, size exclusion chromatography, aqueous two-phase system, and polymer-based precipitation can be used for mass production of exosomes. Though, there is little information about difference in efficiency of exosome isolation among these methods
What is a convenient and standard method for delivering exosomes to the damaged site? As known, exosomes may be clearance by macrophages located on the spleen or the lung tissues, which lower the efficacy of treatment
What is a gold-standard method for purification exosomes?
What is the best storage condition for saving exosomes? For therapeutic application, storage at higher temperatures is desirable because it does not require special equipment. Lyophilization of exosomes may expand their stability at higher temperatures
Do exosomes incorporated into biomaterials have more advantages compared with intact exosomes?