Effect of bone marrow mesenchymal stem cells-derived exosomes on diabetes-induced retinal injury: Implication of Wnt/ b-catenin signaling pathway.

BACKGROUND: Diabetic retinopathy (DR) is a serious microvascular complication of diabetes mellitus. Mesenchymal stem cells are currently studied as therapeutic strategy for management of DR. Exosomes, considered as a promising cell-free therapy option, display biological functions similar to those of their parent cells. In retinal development, Wnt/b-catenin signaling provides key cues for functional progression. The present study aimed to evaluate the potential efficacy of bone marrow-derived mesenchymal stem cell-derived exosomes (BM-MSCs-Ex) in diabetes-induced retinal injury via modulation of the Wnt/ b-catenin signaling pathway. METHODS: Eighty-one rats were allocated into 6 groups (control, DR, DR + DKK1, DR + exosomes, DR + Wnt3a and DR + exosomes+Wnt3a). Evaluation of each group was via histopathological examination, assessment of gene and/or protein expression concerned with oxidative stress (SOD1, SOD2, Nox2, Nox4, iNOS), inflammation (TNF-α, ICAM-1, NF-κB) and angiogenesis (VEGF, VE-cadherin). RESULTS: Results demonstrated that exosomes blocked the wnt/b-catenin pathway in diabetic retina concomitant with significant reduction of features of DR as shown by downregulation of retinal oxidants, upregulation of antioxidant enzymes, suppression of retinal inflammatory and angiogenic markers. These results were further confirmed by histopathological results, fundus examination and optical coherence tomography. Additionally, exosomes ameliorative effects abrogated wnt3a-triggered retinal injury in DR. CONCLUSION: Collectively, these data demonstrated that exosomes ameliorated diabetes-induced retinal injury via suppressing Wnt/ b-catenin signaling with subsequent reduction of oxidative stress, inflammation and angiogenesis.

The potential neuroprotective role of mesenchymal stem cell-derived exosomes in cerebellar cortex lipopolysaccharide-induced neuroinflammation in rats: a histological and immunohistochemical study.

Lipopolysaccharide (LPS) is an endotoxin that prompts neuroinflammation and initiates neurodegenerative disorders. Exosome is a recent therapeutic agent for many diseases such as neurological diseases. This study aimed to evaluate the potential protective role of bone marrow mesenchymal stem cell-derived exosomes (BMSC-EXs) in cerebellar cortex LPS-induced neuroinflammation in rats. Twenty-seven adult male rats were divided into three groups: Group I: control rats; Group II: LPS-treated rats; Group III: LPS/BMSC-EXs-treated rats. Cerebellar specimens were taken and processed for histological and immunohistochemical analysis. Morphometrical studies and statistical analysis were done. Groups II showed neuronal degeneration and apoptosis. The mean number of Purkinje cells was significantly (P<0.01)  decreased, while glial fibrillary acidic protein (GFAP) immunoexpression was significantly increased in the neuroglial cells. Ultrastructural examination showed shrunken Purkinje cells with irregular nuclei and disrupted mitochondria. Group III showed improvement of most of the changes mentioned previously. EXs therapy is a promising neuroprotective tool for treatment of LPS-induced neuroinflammation.

Impacts of resveratrol versus platelet-rich plasma for treatment of experimentally lithium-induced thyroid follicular cell toxicity in rats. A histological and immunohistochemical study.

Lithium (Li) is used for the treatment and prophylaxis of mental disorders, associated with many serious hazards. Resveratrol (RSV) has various beneficial therapeutic effects. Platelet-rich plasma (PRP) is a new promising curative tool. This study aimed to assess the impacts of RSV versus PRP on lithium-induced thyroid follicular cell toxicity in adult male rats. Forty-nine adult male rats were divided into four groups: group I: control rats; group II: lithium-treated rats; group III: lithium- and resveratrol-treated rats; group IV: lithium and PRP-treated rats. Thyroid specimens were taken and processed for histological and immunohistochemical methods. Morphometrical studies and statistical analysis were done. Group II showed distorted thyroid follicles, significantly increased collagen fibers, and highly positive P53 immunostaining (P < 0.01). Ultrastructural examination showed dilated rough endoplasmic reticulum and damaged mitochondria. Groups III and IV exhibited significant amelioration of the histological and electron microscopic changes mentioned previously. PRP remedy was more effective than RSV for treatment of Li-induced thyroid follicular cell toxicity.