Mesenchymal stem cells are a potential therapeutic candidate for cerebral infarction due to their anti-inflammatory proprieties. However, ensuring the engraftment of sufficient cells into the affected brain area remains a challenge. Herein, magnetic targeting techniques were used for the transplantation of a large number of cells noninvasively. Mice subjected to pMCAO surgery were administered MSCs labeled or not with iron oxide@polydopamine nanoparticles by tail vein injection. Iron oxide@polydopamine particles were characterized by transmission electron microscopy, and labeled MSCs were characterized by flow cytometry and their differentiation potential was assessed in vitro. Following the systemic injection of iron oxide@polydopamine-labeled MSCs into pMCAO-induced mices, magnetic navigation increased the MSCs localization to the brain lesion site and reduced the lesion volume. Treatment with iron oxide@polydopamine-labeled MSCs also significantly inhibited M1 microglia polarization and increased M2 microglia cell infiltration. Furthermore, western blotting and immunohistochemical analysis demonstrated that microtubule-associated protein 2 and NeuN levels were upregulated the brain tissue of mice treated with iron oxide@polydopamine-labeled MSCs. Thus, iron oxide@polydopamine-labeled MSCs attenuated brain injury and protected neurons by preventing pro-inflammatory microglia activation. Overall, the proposed iron oxide@polydopamine-labeled MSCs approach may overcome the major drawback of the conventional MSCs therapy for the treatment of cerebral infarction.

Abstract Mesenchymal stem cell-derived exosomes (MSCs-exo) can be used for treating Alzheimer’s disease (AD) by promoting amyloid-β (Aβ) degradation, modulating immune responses, protecting neurology, promoting axonal growth, and improving cognitive impairment. Increasing evidence suggests that the alteration of gut microbiota is closely related to the occurrence and development of Alzheimer's disease. In this study, we hypothesized that dysbiosis of gut microbiota might limit the effectiveness of MSCs-exo, whereas regulating the gut microbiota would improve the therapy of MSCs-exo. Methods: In this original research study, we used MSCs-exo to treat 5×FAD mice and fed them antibiotic cocktails for 1 week to detect cognitive ability and neuropathy. The mice’s feces were collected to investigate alterations in the microbiota and metabolites. Results: The results revealed that the AD gut microbiota eliminated the therapeutic effect of MSCs-exo, whereas antibiotic modulation of disordered gut microbiota and associated metabolites enhanced the therapeutic effect of MSCs-exo. Conclusions: These results encourage the research of novel therapeutics to enhance MSCs-exo treatment for AD, which could benefit a broader range of patients with AD.

Fe3O4 nanoparticles are widely used in the diagnosis and treatment of diseases due to their superparamagnetism, but their toxicity in vivo, which can result in apoptosis or autophagy, cannot be ignored. It has been reported that polydopamine (PDA) modification can reduce the toxicity of Fe3O4 and increase its biocompatibility. However, more research is warranted to further improve the modification method. We therefore developed a new method to coat Fe3O4@PDA nanoparticles with the mesenchymal stem cell membrane (MSCM) and evaluated the toxicity of the modified particles in the lungs of mice. We found that the MSCM modification significantly reduced lung injury induced by Fe3O4 particles in mice. Compared with Fe3O4@PDA nanoparticles, co-modification with MSCM and PDA significantly reduced autophagy and apoptosis in mouse lung tissue, and reduced activation of autophagy mediated by the AMPK-ULK1 pathway axis. Thus, co-modification with MSCM and PDA prevents Fe3O4-induced pulmonary toxicity in mice by inhibiting autophagy, apoptosis, and oxidative stress.

Background: Fe3O4 nanoparticles are widely used in the diagnosis and treatment of diseases, but the toxicity should not be ignored. It has been reported that PDA modification can reduce the toxicity of Fe3O4 and increase the biocompatibility. However, a better modification method is still worth studying. We have developed a new method to coat Fe3O4@PDA nanoparticles with mesenchymal stem cells membrane (MSCM) and evaluated the lung toxicity of the modified particles to mice.Result: We found that MSCM modification significantly reduced the lung injury induced by Fe3O4 nanoparticles in mice. Compared with Fe3O4@PDA nanoparticles, co-modification with MSCM and PDA modification significantly reduced autophagy and apoptosis of mouse lung tissue, and reduced the activation of autophagy pathway AMPK-ULK1 axis. Thus, co-modification with MSCM and PDA prevents Fe3O4-induced pulmonary toxicity in mice by inhibiting the AMPK-ULK1 derived autophagy.Conclusion: MSCM coated Fe3O4@PDA nanoparticles were demonstrated to prevent lung damage from autophagy and reduce the toxicity of iron oxide nanomaterials. The co-modification of PDA and MSCM can improve the biocompatibility and facilitate their further bioapplication.

Purpose Nanoparticle (NP)-based chemo-photothermal therapy (CPT) has been shown to be a promising non-invasive approach for antitumor treatment. However, NPs must overcome the limitations of opsonization, clearance of the reticuloendothelial system, and ineffective targeting of tumor tissue sites. To solve these problems, stem cell membrane (SCM)-camouflaged polydopamine nanoparticles (PDA@SCM NPs) carrying the hydrophobic anticancer drug 7-ethyl-10-hydroxycamptothecin (SN38) were constructed for CPT of malignant bone tumors. Methods We developed umbilical-cord mesenchymal stem cell membrane-coated polydopamine nanoparticles encapsulating SN38 (PDA-SN38@SCM NPs) as an efficient tumor-targeting drug-delivery platform for CPT of malignant bone tumors. We characterized PDA@SCM NPs and evaluated the biocompatibility and anti-phagocytosis properties of PDA@SCM NPs. The antitumor activity of PDA-SN38@SCM NPs was evaluated in MG63 lines and an MG63 xenograft model in mice. Results Synthesized PDA-SN38@SCM NPs retained an excellent photothermal effect after SN38 loading. The drug release of PDA-SN38@SCM NPs could be triggered by near-infrared irradiation and an acidic stimulus. PDA@SCM NPs exhibited lower nonspecific macrophage uptake, longer retention in blood, and more effective accumulation at tumor sites than that shown by PDA NPs. Confocal laser scanning microscopy (CLSM) and flow cytometry showed that MG63 cells took up more PDA-SN38@SCM NPs than PDA-SN38 NPs. In vitro and in vivo antitumor studies demonstrated the outstanding performance of PDA-SN38@SCM NPs in synergistic CPT for bone tumors. Conclusion PDA-SN38@SCM NPs demonstrated an extraordinary synergistic CPT effect and could be a promising strategy for the treatment of malignant bone tumors.