Significance: This study demonstrated that intranasal (IN) administration of A1-exosomes alleviates multiple adverse changes that typically emerge after status epilepticus (SE), a medical crisis that presents a high propensity to evolve into chronic hippocampus dysfunction. Specifically, A1-exosome treatment after SE led to reduced neuron loss and inflammation, maintenance of normal neurogenesis, and preservation of cognitive and memory function. The results have significance for clinical application of A1-exosomes for curbing the evolution of SE-induced injury into chronic hippocampus dysfunction. The results also imply that IN administration of A1-exosomes is therapeutic for other neurological conditions that present with significant neuroinflammation.

Mesenchymal stem cell-derived exosomes (MSC-Exo) have robust anti-inflammatory effects in the treatment of neurological diseases such as epilepsy, stroke, or traumatic brain injury. While astrocytes are thought to be mediators of these effects, their precise role remains poorly understood. To address this issue, we investigated the putative therapeutic effects and mechanism of MSC-Exo on inflammation-induced alterations in astrocytes.

Diabetic wound shows delayed and incomplete healing processes, which in turn exposes patients to an environment with a high risk of infection. This article has summarized current developments of nanoparticles/hydrogels and nanotechnology used for promoting the wound healing process in either diabetic animal models or patients with diabetes mellitus. These nanoparticles/hydrogels promote diabetic wound healing by loading bioactive molecules (such as growth factors, genes, proteins/peptides, stem cells/exosomes, etc.) and non-bioactive substances (metal ions, oxygen, nitric oxide, etc.). Among them, smart hydrogels (a very promising method for loading many types of bioactive components) are currently favored by researchers. In addition, nanoparticles/hydrogels can be combined with some technology (including PTT, LBL self-assembly technique and 3D-printing technology) to treat diabetic wound repair. By reviewing the recent literatures, we also proposed new strategies for improving multifunctional treatment of diabetic wounds in the future.

Neurodegenerative diseases are characterized by the progressive loss of neurons and intricate interactions between different cell types within the affected regions. Reliable biomarkers that can accurately reflect disease activity, diagnose, and monitor the progression of neurodegenerative diseases are crucial for the development of effective therapies. However, identifying suitable biomarkers has been challenging due to the heterogeneous nature of these diseases, affecting specific subsets of neurons in different brain regions. One promising approach for promoting brain regeneration and recovery involves the transplantation of mesenchymal stem cells (MSCs). MSCs have demonstrated the ability to modulate the immune system, promote neurite outgrowth, stimulate angiogenesis, and repair damaged tissues, partially through the release of their extracellular vesicles (EVs). MSC-derived EVs retain some of the therapeutic characteristics of their parent MSCs, including their ability to regulate neurite outgrowth, promote angiogenesis, and facilitate tissue repair. This review aims to explore the potential of MSC-derived EVs as an emerging therapeutic strategy for neurodegenerative diseases, highlighting their role in modulating disease progression and promoting neuronal recovery. By elucidating the mechanisms by which MSC-derived EVs exert their therapeutic effects, we can advance our understanding and leverage their potential for the development of novel treatment approaches in the field of neurodegenerative diseases.

Mesenchymal stem cell-derived small extracellular vesicles (MSC-EVs) are promising nanotherapeutic agent for pneumonia (bacterial origin, COVID-19), but the optimal administration route and potential mechanisms of action remain poorly understood. This study compared the administration of MSC-EVs via inhalation and tail vein injection for the treatment of acute lung injury (ALI) and determined the host-derived mechanisms that may contribute to the therapeutic effects of MSC-EVs in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells (macrophage cell line) and animal models. Luminex liquid chip and hematoxylin and eosin (HE) staining revealed that, compared with the vehicle control, inhaled MSC-EVs outperformed those injected via the tail vein, by reducing the expression of pro-inflammatory cytokines, increasing the expression of anti-inflammatory cytokine, and decreasing pathological scores in ALI. MSC-EV administration promoted the polarization of macrophages towards a M2 phenotype in vitro and in vivo (via inhalation). RNA sequencing revealed that immune and redox mediators, including TLR4, Arg1, and HO-1, were associated with the activity MSC-EVs against ALI mice. Western blotting and immunofluorescence revealed that correlative inflammatory and oxidative mediators were involved in the therapeutic effects of MSC-EVs in LPS-stimulated cells and mice. Moreover, variable expression of Nrf2 was observed following treatment with MSC-EVs in cell and animal models, and knockdown of Nrf2 attenuated the anti-inflammatory and antioxidant activities of MSC-EVs in LPS-stimulated macrophages. Together, these data suggest that inhalation of MSC-EVs as a noninvasive strategy for attenuation of ALI, and the adaptive regulation of Nrf2 may contribute to their anti-inflammatory and anti-oxidant activity in mice.