Neonatal Tissue-derived Extracellular Vesicle Therapy (NEXT): A Potent Strategy for Precision Regenerative Medicine.

Extracellular vesicle (EV)-based therapies have emerged as a promising means in regenerative medicine. However, the conventional EV therapy strategy (using EVs from a single type of cultured cell) displays some limitations, such as inefficient EV production and lack of tissue-specific repair effects. Here, we report that neonatal tissue-derived EV therapy (NEXT) is a potent strategy for precision tissue repair. In brief, large amounts of EVs with higher yield/purity can be readily isolated from desired tissues with less production time/cost compared to the conventional cell culture-based method. Moreover, source factors, such as age and tissue type, can affect the repair efficacy of such tissue-derived EVs in different tissue injury models (skin wounds and acute kidney injury), and neonatal tissue-derived EVs show superior tissue repair potency compared with adult tissue-derived EVs. Different age- or tissue type-derived EVs have distinct composition (e.g., protein) signatures that are likely due to the diverse metabolic patterns of the donor tissues, which may contribute to the specific repair action modes of NEXT in different types of tissue injury. Furthermore, neonatal tissue-derived EVs can be incorporated with bioactive materials (e.g., artificial ECM hydrogel) for advanced tissue repair. This study highlights that our NEXT strategy may provide a new avenue for precision tissue repair in many types of tissue injury. This article is protected by copyright. All rights reserved.