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Abstract Background Machado-Joseph disease is the most common autosomal dominant hereditary ataxia worldwide without effective treatment. Mesenchymal stem cells (MSCs) could slow the disease progression, but side effects limited their clinical application. Besides, MSC-derived exosomes exerted similar efficacy and have many advantages over MSCs. The aim of this study was to examine the efficacy of MSC-derived exosomes in YACMJD84.2 mice. Methods Rotarod performance was evaluated every 2 weeks after a presymptomatic administration of intravenous MSC-derived exosomes twice in YACMJD84.2 mice. Loss of Purkinje cells, relative expression level of Bcl-2/Bax, cerebellar myelin loss, and neuroinflammation were assessed 8 weeks following treatment. Results MSC-derived exosomes were isolated and purified through anion exchange chromatography. Better coordination in rotarod performance was maintained for 6 weeks in YACMJD84.2 mice with exosomal treatment, compared with those without exosomal treatment. Neuropathological changes including loss of Purkinje cells, cerebellar myelin loss, and neuroinflammation were also attenuated 8 weeks after exosomal treatment. The higher relative ratio of Bcl-2/Bax was consistent with the attenuation of loss of Purkinje cells. Conclusions MSC-derived exosomes could promote rotarod performance and attenuate neuropathology, including loss of Purkinje cells, cerebellar myelin loss, and neuroinflammation. Therefore, MSC-derived exosomes have a great potential in the treatment of Machado-Joseph disease.

Abstract Background Human induced pluripotent stem cells-derived mesenchymal stem cells (iPSC-MSCs) have been shown to be effective in Type 2 helper T cells (Th2)-dominant eosinophilic allergic airway inflammation. However, the role of iPSC-MSCs in Type 17 helper T cells (Th17)-dominant neutrophilic airway inflammation remains poorly studied. Therefore, this study was to explore the effects of iPSC-MSCs on an experimental mouse model of steroid-resistant neutrophilic airway inflammation and further determine the underlying mechanisms. Methods A mouse model of neutrophilic airway inflammation was established using ovalbumin (OVA) and lipopolysaccharide (LPS). Human iPSC-MSCs were systemically administered, and the lungs or bronchoalveolar lavage fluids (BALF) were collected at 4 h and 48 h post-challenge. The pathology and inflammatory cell infiltration, the T helper cells, T helper cells-associated cytokines, nuclear transcription factors and possible signaling pathways were evaluated. Human CD4+ T cells were polarized to T helper cells and the effects of iPSC-MSCs on the differentiation of T helper cells were determined. Results We successfully induced the mouse model of Th17 dominant neutrophilic airway inflammation. Human iPSC-MSCs but not dexamethasone significantly prevented the neutrophilic airway inflammation and decreased the levels of Th17 cells, IL-17A and p-STAT3. The mRNA levels of Gata3 and RORγt were also decreased with the treatment of iPSC-MSCs. We further confirmed the suppressive effects of iPSC-MSCs on the differentiation of human T helper cells. Conclusions iPSC-MSCs showed therapeutic potentials in neutrophilic airway inflammation through the regulation on Th17 cells, suggesting that the iPSC-MSCs could be applied in the therapy for the asthma patients with steroid-resistant neutrophilic airway inflammation.

Background: Mesenchymal stem cells (MSCs) have potent immunomodulatory effects on multiple immune cells and have great potential in treating immune disorders. Induced pluripotent stem cells (iPSCs) serve as an unlimited and noninvasive source of MSCs, and iPSC-MSCs have been reported to have more advantages and exhibit immunomodulation on T lymphocytes and natural killer cells. However, the effects of iPSC-MSCs on dendritic cells (DCs) are unclear. The aim of this study is to investigate the effects of iPSC-MSCs on the differentiation, maturation, and function of DCs. Methods: Human monocyte-derived DCs were induced and cultured in the presence or absence of iPSC-MSCs. Flow cytometry was used to analyze the phenotype and functions of DCs, and enzyme-linked immunosorbent assay (ELISA) was used to study cytokine production. Results: In this study, we successfully induced MSCs from different clones of human iPSCs. iPSC-MSCs exhibited a higher proliferation rate with less cell senescence than BM-MSCs. iPSC-MSCs inhibited the differentiation of human monocyte-derived DCs by both producing interleukin (IL)-10 and direct cell contact. Furthermore, iPSC-MSCs did not affect immature DCs to become mature DCs, but modulated their functional properties by increasing their phagocytic ability and inhibiting their ability to stimulate proliferation of lymphocytes. More importantly, iPSC-MSCs induced the generation of IL-10-producing regulatory DCs in the process of maturation, which was mostly mediated by a cell-cell contact mechanism. Conclusions: Our results indicate an important role for iPSC-MSCs in the modulation of DC differentiation and function, supporting the clinical application of iPSC-MSCs in DC-mediated immune diseases. [ABSTRACT FROM AUTHOR]