In women of reproductive age, severe injuries to the ovary are often accompanied by premature ovarian failure (POF), which can result in amenorrhea or infertility. Hormone replacement therapy has been used to treat POF; however, it has limited therapeutic efficiency and may cause several side effects. In this study, we aimed to fabricate a Matrigel scaffold loaded with human umbilical cord-derived mesenchymal stem cells (MSCs) and explore its potential to restore ovarian function and repair ovarian structures in vitro and in vivo. POF mouse models were established by injecting mice with cyclophosphamide for 15 consecutive days. Then, MSC/Matrigel was transplanted into the ovaries of the mice. Five weeks later, the morphology of the ovaries and follicles was observed by hematoxylin/eosin staining, and the tissue fibrosis ratio was measured using Masson's trichrome staining. The number of blood vessels was evaluated by α-smooth muscle actin and CD31 immunofluorescence, and Ki67 expression was used to determine the proliferation of granulosa cells. The expression of vascular endothelial growth factor (VEGF)-A was assessed by western blotting. The Matrigel scaffold regulated the expression of VEGF-A in vitro. Moreover, it promoted MSC survival and proliferation and prevented MSC apoptosis in vivo. After the transplantation of the MSC/Matrigel, the number of follicles was significantly increased in the mice with POF, and the tissue fibrosis ratio was reduced. Furthermore, the MSC/Matrigel significantly improved the proliferation rate of granulosa cells, increased the number of blood vessels, and upregulated the expression of VEGF-A. These findings demonstrate that MSC/Matrigel may support follicular development and help restore ovarian structures in vivo.

Amyloid-β, one of the hallmarks of Alzheimer’s disease (AD), is toxic to neurons and can also cause brain cell death. Oxidative stress is known to play an important role in AD, and there is strong evidence that oxidative stress is associated with amyloid-β. In the present study we report the protective effect of Zijuan Pu’er tea water extract (ZTWE) and the mixture of main ingredients (+)-catechins, caffeine and procyanidin (MCCP) in ZTWE on β-amyloid-induced toxicity in transgenic Caenorhabditis elegans (C. elegans) CL4176 expressing the human Aβ_1–42 gene. ZTWE, (+)-catechins, caffeine, procyanidin and MCCP delayed the β-amyloid-induced paralysis to different degrees. The MCCP treatment did not affect the transcript abundance of amyloid-β transgene (amy-1); however, Thioflavin T staining showed a significant decrease in Aβ accumulation compared to untreated worms. Further research using transgenic worms found that MCCP promoted the translocation of DAF-16 from cytoplasm to nucleus and increased the expression of superoxide dismutase 3 (SOD-3). In addition, MCCP decreased the reactive oxygen species (ROS) content and increased the SOD activity in CL4176 worms. In conclusion, the results suggested that MCCP had a significant protective effect on β-amyloid-induced toxicity in C. elegans by reducing β-amyloid aggregation and inducing DAF-16 nuclear translocation that could activate the downstream signal pathway and enhance resistance to oxidative stress.

MiRNAs have been shown to be involved in the regulation of a variety of physiological and pathological processes, but their use in the treatment of diseases is still limited due to their instability. Biomimetic nanomaterials combine nanomaterials with cellular components that are readily modifiable and biocompatible, making them an emerging miRNA delivery vehicle. In this study, adipose-derived MSC membranes were wrapped around PLGA-PEI loaded with miR-21 through co-extrusion and later transplanted into C57BL/6 mice wounds. The wound-healing rate, epithelialization, angiogenesis, and collagen deposition were assessed after treatment and corroborated in vitro. Our study demonstrated that m/NP/miR-21 can promote wound healing in terms of epithelialization, dermal reconstruction, and neovascularization, and it can regulate the corresponding functions of keratinocytes, fibroblasts, and vascular endothelial cells. m/NP/miR-21 can inhibit the expression of PTEN, a gene downstream of miR-21, and increase the phosphorylation activation of AKT, which can then regulate the functions of fibroblasts. In conclusion, this provides a new approach to therapy for skin wounds using microRNA transporters and biomimetic nanoparticles.

Diabetes mellitus (DM) has reached pandemic prevalence, significantly impacting global health. Accumulating evidence has highlighted a bidirectional relationship between diabetes and depression, with blood–brain barrier (BBB) disruption playing a pivotal role in the pathogenesis of and therapeutic approaches to both disorders. Mesenchymal stem cells (MSCs) have emerged as a promising cell-based therapeutic strategy for DM; however, their potential to mitigate DM-associated emotional deficits remains unclear. This study investigates whether MSCs can restore BBB integrity and improve emotional deficits in a diabetic mouse model via matrix metalloprotein-9 (MMP-9) inhibition. We used biochemical, molecular, and behavioral analyses to assess BBB function, inflammation, and emotional behavior. Our results demonstrated that diabetic conditions induce BBB dysfunction, characterized by the MMP-9-mediated degradation of tight junction (TJ) proteins claudin-5 (Cldn5) and occludin (Ocln), alongside neuroinflammation and emotional impairments. Notably, MSC administration restored BBB integrity and attenuated neuroinflammation by suppressing MMP-9 activity and upregulating TJ proteins. Importantly, MSC treatment not only alleviated anxiety- and depressive-like behaviors but also enhanced glycemic control in DMmodels. These findings elucidate the mechanistic basis of MSC therapy for DM-related neuropsychiatric complications and, crucially, reveal its dual therapeutic efficacy in concurrently ameliorating both neuropsychiatric symptoms and metabolic dysfunction in DM models. This synergistic therapeutic effect provides a translational rationale for advancing MSC-based therapies into clinical applications.

Introduction: Mesenchymal stem cells (MSCs) have been introduced as a promising treatment for diabetic wounds. The effects of stem cell therapy are thought to be caused by bioactive molecules secreted by stem cells. Stem cell-based gene therapies can target bioactive molecules. Therefore, treatment using conditioned medium (CM) derived from genetically engineered stem cells has been proposed as an alternative option for diabetic ulcer care. Methods: MSCs derived from human umbilical cords were obtained and engineered to overexpress the angiogenin-1 gene (MSCs^Ang1) through plasmid transfection. This study extracted conditioned medium from MSCs (MSC-CM) or MSCs^Ang1(MSC^Ang1-CM) for wound treatment applications. Via in vitro experiments, the proangiogenic effects of MSC^Ang1-CM were assessed via the migration and tube formation of human umbilical vein endothelial cells (HUVECs). Furthermore, the efficacy of MSC^Ang1-CM in promoting wound healing, re-epithelialization, hair follicle, and angiogenesis was evaluated via a diabetic mouse skin defect model. Results: In vitro assays demonstrated that MSC^Ang1-CM significantly enhanced HUVECs’ functions, including migration and tube formation. In vivo assays revealed that MSC^Ang1-CM exhibited notable advancements in healing speed, re-epithelialization, hair follicle, and angiogenesis. Conclusion: These results indicate that MSC^Ang1-CM can promote wound healing in diabetic mice and make the vascular structure in regenerated tissues more stable without inducing tissue fibrosis, providing a new therapeutic strategy for treating diabetic skin wounds. This provides a valuable theoretical basis for further research on regenerative medicine and cell therapy.