Human mesenchymal stem cell (MSC)-derived exosomes (Exos) are a promising therapeutic agent for cell-free regenerative medicine. However, their poor organ-targeting ability and therapeutic efficacy have been found to critically limit their clinical applications. In the present study, we fabricated iron oxide nanoparticle (NP)-labeled exosomes (Exo + NPs) from NP-treated MSCs and evaluated their therapeutic efficacy in a clinically relevant model of skin injury. We found that the Exos could be readily internalized by human umbilical vein endothelial cells (HUVECs), and could significantly promote their proliferation, migration, and angiogenesis both in vitro and in vivo. Moreover, the protein expression of proliferative markers (Cyclin D1 and Cyclin A2), growth factors (VEGFA), and migration-related chemokines (CXCL12) was significantly upregulated after Exo treatment. Unlike the Exos prepared from untreated MSCs, the Exo + NPs contained NPs that acted as a magnet-guided navigation tool. The in vivo systemic injection of Exo + NPs with magnetic guidance significantly increased the number of Exo + NPs that accumulated at the injury site. Furthermore, these accumulated Exo + NPs significantly enhanced endothelial cell proliferation, migration, and angiogenic tubule formation in vivo; moreover, they reduced scar formation and increased CK19, PCNA, and collagen expression in vivo. Collectively, these findings confirm the development of therapeutically efficacious extracellular nanovesicles and demonstrate their feasibility in cutaneous wound repair.

The Fe ₃ O ₄ @PDA NPs enhanced the recruitment of MSCs and improved the anti-inflammatory and healing ability compared with the MSC treatment alone.

Introduction: Mesenchymal stem cells (MSCs) are a promising resource for tissue regeneration and repair. However, their clinical application is hindered by technical limitations related to MSC enrichment at the target sites. Methods: MSCs were labeled with magnetic Fe₃O₄ nanoparticles (NPs). We analyzed the effects of NP on cell proliferation, stem cell characteristics, and cytokine secretion. Furthermore, we induced NP-labeled MSC migration with an external magnetic field toward laser-induced skin wounds in rats and evaluated the associated anti-inflammatory effects. Results: Fe₃O₄ NP application did not adversely affect MSC characteristics. Moreover, Fe₃O₄ NP-labeled MSCs presented increased anti-inflammatory cytokine and chemokine production compared with unlabeled MSCs. Furthermore, MSCs accumulated at the injury site and magnetic targeting promoted NP-labeled MSC migration toward burn injury sites in vivo. On day 7 following MSC injection, reduced inflammation and promoted angiogenesis were observed in the magnetically targeted MSC group. In addition, anti-inflammatory factors were upregulated, whereas pro-inflammatory factors were downregulated within the magnetically targeted MSC group compared with those in the PBS group. Conclusion: This study demonstrates that magnetically targeted MSCs contribute to cell migration to the site of skin injury, improve anti-inflammatory effects and enhance angiogenesis compared with MSC injection alone. Therefore, magnetically targeted MSC therapy may be an effective treatment approach for epithelial tissue injuries.

Introduction: Exosomes (Exos) are promising drug delivery systems due to their low immunogenicity, minimal toxicity, high biocompatibility, and effective delivery capabilities. However, addressing the cardiotoxicity and other toxic side effects associated with anthracyclines has proven challenging. Methods: In this study, we loaded doxorubicin (Dox) into Exos derived from human placental mesenchymal stem cells (MSCs) and modified them with carboxylated Fe₃O₄ nanoparticles (NPs) to create an Exo-Dox-NP delivery system. Using an external magnetic force (MF), we regulated the distribution of Exos for targeted Dox delivery in breast cancer treatment. We characterized and determined the drug-loading efficiency of Exo-Dox-NPs, their uptake by tumor cells, and the modulation of drug release. The therapeutic efficacy of Exo-Dox-NPs was evaluated through both in vitro and in vivo anti-tumor experiments. Results: Our results indicated that Exo-Dox-NPs remain stable in the bloodstream while releasing the drug in the acidic environment of tumor cells and their lysosomes. As a drug delivery system, Exo-Dox-NPs enhanced Dox absorption by tumor cells, demonstrating high targeting specificity. Moreover, Exo-Dox-NPs inhibited the migration of breast cancer cells, as confirmed by scratch migration and Transwell Matrigel invasion assays. In vivo experiments confirmed the effective targeting and delivery of Dox to malignant tumors using Exo-Dox-NPs/MFs, with the Exo-Dox-NP/MF formulation exhibiting the most potent anti-tumor activity. Conclusion: The utilization of Exos as carriers for Dox showed promising efficacy in breast cancer management. Carboxylated Fe₃O₄ NPs demonstrated to be suitable targeting agents, potentially advancing the development of natural nanocarriers for combination cancer therapy.

Diabetes mellitus (DM) is characterized by the irreversible destruction of insulin-secreting pancreatic β-islet cells and requires life-long exogenous insulin therapy. Umbilical cord Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have been shown to improve islet function in animal models of diabetes. However, inadequate MSC homing to injured sites has limited their efficacy. Since efficient cell therapy heavily relies on appropriate homing to target tissues, increasing the specificity to the target organ and the extent of homing of the injected WJ-MSCs is paramount to successful clinical outcomes. Therefore, in this study, we synthesized Fe₃O₄@polydopamine nanoparticle (NP)-labeled MSCs and evaluated their therapeutic efficacy in a clinically relevant rat model of streptozotocin-induced diabetes using an external magnetic field. We found that NPs were successfully incorporated into WJ-MSCs and did not negatively affect stem cell properties. Magnetic targeting of WJ-MSCs contributed to long-term cell retention in pancreatic tissue and improved the islet function of diabetic rats, compared to injection of WJ-MSC alone. In addition, anti-inflammatory effects and the anti-apoptotic capacity of WJ-MSCs appeared to play a major role in the functional and structural recovery of the pancreas. Thus, therapy relying on the magnetic targeting of WJ-MSCs may serve as an effective approach for DM treatment.

Increasing evidence has indicated that circulating placental RNAs may reflect the pathophysiology of the placenta. In the current study, circulating placenta-related long noncoding RNAs (lncRNAs) were evaluated as potential biomarkers for preeclampsia (PE). Two parts of the case‑control study were simultaneously executed, including the following sets: 52 patients with late‑onset PE (LOPE) (diagnosed after 34 weeks) and 52 gestational age (GA)‑matched controls; 58 patients with early‑onset PE (EOPE) (diagnosed before 34 weeks) and 58 GA‑matched controls. LncRNA expression was detected in the placenta analysis part, and the participants were delivered by caesarean sections. The levels of circulating placenta-associated lncRNAs were measured in the plasma analysis part and all pregnant women were included. Using microarray analysis, 163 differentially expressed lncRNAs were identified in placental samples from patients with LOPE, some of which were also detected in plasma samples from pregnant women. There were significant positive correlations between plasma, and placental expression levels of NONHSAT116812 and NONHSAT145880, which in plasma provided high diagnostic efficiencies for LOPE and EOPE. The present study demonstrated that circulating placenta‑associated lncRNAs, paticularly NONHSAT116812 and NONHSAT145880 have potential as biomarkers for PE.