Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidates for cell-free treatment of various diseases. However, maintaining the retention and stability of exosomes over time in vivo after transplantation is a major challenge in the clinical application of MSC-derived exosomes. Here, we investigated if human placenta-derived MSC-derived exosomes incorporated with chitosan hydrogel could boost the retention and stability of exosomes and further enhance their therapeutic effects. Our results demonstrated that chitosan hydrogel notably increased the stability of proteins and microRNAs in exosomes, as well as augmented the retention of exosomes in vivo as confirmed by Gaussia luciferase imaging. In addition, we assessed endothelium-protective and proangiogenesis abilities of hydrogel-incorporated exosomes in vitro. Meanwhile, we evaluated the therapeutic function of hydrogel-incorporated exosomes in a murine model of hindlimb ischemia. Our data demonstrated that chitosan hydrogel could enhance the retention and stability of exosomes and further augment the therapeutic effects for hindlimb ischemia as revealed by firefly luciferase imaging of angiogenesis. The strategy used in this study may facilitate the development of easy and effective approaches for assessing and enhancing the therapeutic effects of stem cell-derived exosomes.

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Extracellular vesicles (EVs) attract much attention in liver pathology because they regulate cell–cell communication and many pathophysiological events by transferring their cargos. Monitoring and understanding the in vivo fate and therapeutic capacity of these EVs is critical for the development and optimization of EV-based diagnosis and therapy. Herein, we demonstrate the use of an aggregation-induced emission luminogen, DPA-SCP, for the real-time tracking of EVs derived from human placenta-derived mesenchymal stem cells (MSCs) and their therapeutic effects in a mouse acute liver injury (ALI) model. In vitro, DPA-SCP does not alter the inherent characteristics of MSC-derived EVs and shows extremely low toxicity. Moreover, DPA-SCP exhibited superior labeling efficiency and tracking capability to the most popular commercial EV trackers, PKH26 and DiI. In vivo, DPA-SCP precisely and quantitatively tracked the behaviors of EVs for 7 days in the mouse ALI model without influencing their regenerative capacity and therapeutic efficacy. The therapeutic effects of EVs may attribute to their ability for reducing inflammatory cell infiltration, enhancing cell survival and antiapoptotic effects. In conclusion, DPA-SCP with an AIE signature serves as a favorable and safe tracker for in vivo real-time imaging of EVs in liver regeneration.

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With the immunoregulation potential, mesenchymal stem cells (MSCs) have been used for tissue regeneration by relieving inflammation in the injured tissues. When this repair process is interfered by immune disorders or pathological angiogenesis, the delays in corneal epithelial wound healing can lead to a persistent epithelial defect. Stem cell-derived extracellular vesicles (EVs), which carry abundant bioactive molecules from stem cells, have provided an alternative to regeneration therapy. In this study, we aimed to investigate if EVs from human placenta-derived MSCs (hP-MSCs) could ameliorate alkali injury of the cornea in the mouse model. 33.33 μg/μL EVs in 10 μL PBS were applied to the cornea. Repeat application three times, and 100 μg EVs (in 30 μL PBS) in total were administrated per day for two weeks. Our results revealed that EVs from hP-MSCs had preferable functions including enhancing proliferation and anti-inflammation and suppressing apoptosis of corneal epithelial cells. Furthermore, hP-MSC-derived EVs ameliorated mouse corneal wound healing by inhibiting angiogenesis and inflammation. Taken together, our current data suggested that hP-MSC-derived EVs have the beneficial effects of corneal wound healing, which provide alternative cell-free therapy with great practical value.

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