Neonatal‐Tissue‐Derived Extracellular Vesicle Therapy (NEXT): A Potent Strategy for Precision Regenerative Medicine

Abstract

Extracellular vesicle (EV)‐based therapies have emerged as a promising means in regenerative medicine. However, the conventional EV therapy strategy displays some limitations, such as inefficient EV production and lack of tissue‐specific repair effects. Here, it is reported 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 for advanced tissue repair. This study highlights that the NEXT strategy may provide a new avenue for precision tissue repair in many types of tissue injury.

Liver regeneration requires reciprocal release of tissue vesicles to govern rapid hepatocyte proliferation

“…Next, we intended to investigate that whether EVs are indeed involved in the liver regeneration process. Ti-EVs putatively exist in the tissue extracellular space and reflect pathophysiological features of the tissue [14, 15]. However, current studies examine Ti-EVs mainly via enzymatic digestion and isolation, resulting in loss of spatiotemporal information and potential compromise of EV amount and integrity [17–19].…”

“…These membranous nanoparticles are discovered to escape from the autophagy-lysosomal pathway and be release into the circulation and the extracellular space of tissues [30, 31]. Particularly, studies have shown the potential of Ti-EVs in promoting tissue regeneration, and LT-EVs have been employed to expedite the hepatic disease recovery process [15, 16]. However, the specific cellular origin of Ti-EVs responsible for the action remains unknown.…”

Nutrient availability regulates the secretion and function of immune cell–derived extracellular vesicles through metabolic rewiring

“…Each method offers unique benefits and limitations in quantifying EVs based on size, concentration, and other characteristics ( 15 ). Here, EV yield was assessed using the most common method, that is, determining the ratio of the protein concentration of EVs to the protein concentration of donor cells ( 16 ). The results showed that changes in the individual nutrient contents altered the EV yield of M0-Mφs to some extent ( Fig.…”

“…M0-Mφs or M1-Mφs were cultured in RPMI 1640 supplemented with EV-depleted FBS and subjected to the indicated nutrient conditions for 24 hours. Then, the culture medium was collected and subjected to EV isolation via a differential centrifugation method ( 16 ). In brief, the medium was centrifuged at 300 g for 10 min and at 2000 g for 30 min at 4°C to remove cells and other debris, followed by ultracentrifugation at 110,000 g for 90 min at 4°C in an SW32Ti rotor (Beckman Coulter, Brea, CA, USA) to obtain EVs.…”

A Review of the Use of Extracellular Vesicles in the Treatment of Neonatal Diseases: Current State and Problems with Translation to the Clinic

“…Emerging evidence suggests that the therapeutic efficacy of tissue-specific EVs may be highly dependent on the age of the donor. For example, kidney tissue-derived EVs from newborn rat pups after acute injury showed a more pronounced reparative effect on the kidneys of mice than EVs derived from adult animals [ 108 ]. A correlation was found between the increasing age of the donor and a decrease in the neuroprotective effect of bone marrow-derived MSCs [ 109 ].…”