Mesenchymal stem cell‐conditioned medium attenuates the retinal pathology in amyloid‐β‐induced rat model of Alzheimer's disease: Underlying mechanisms

Kuo, Shu‐Chun; Chio, Chung-Ching; Yeh, Chao‐Hung; Ma, Jui-Ti; Liu, Wen-Pin; Lin, Mao‐Tsun; Lin, Kao‐Chang; Chang, Ching‐Ping

doi:10.1111/acel.13340

Cited by 17 publications

(8 citation statements)

References 48 publications

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“…This led to neuroprotection in the CNS, improving cell survival by inhibiting neuronal apoptosis, promoting cell proliferation, promoting cell regeneration, and preventing b amyloid deposition. ( Kuroda et al , 2020 ; Saha et al ., 2020 ; Kuo et al ., 2021 ; Park et al ., 2021 ; Alidous et al ., 2023 ) ( Fig. 7 ).…”

Section: Search Resultsmentioning

confidence: 99%

Chitosan hydrogel nanoparticle enhance therapeutic effect of bovine umbilical mesenchymal stem cell conditioned medium on canine cognitive dysfunction or canine alzheimer’s like mediated by inhibition of neuronal apoptotic

Wihadmadyatami,

Zulfikar,

Herawati

et al. 2023

Open Vet J

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In treating brain diseases, such as canine cognitive dysfunction, most currently available potent drugs have weak therapeutic efficacy. One of the causes is the inability of the substance to reach the brain in therapeutic quantities. These pharmaceuticals lacked targeted mechanisms for drug delivery, coming about in an elevated drugs concentration in imperative organs, which driven to drug harmfulness. In recent years, cell-free treatment (conditioned medium) determined from animal and human stem cells have provided new promise for treating brain diseases, as CM can stimulate the regeneration of neurons and prevent the inflammation and apoptotic of neurons caused by pathology or aging. On the other hand, it is well known that Chitosan-Hydrogel (CH) is a polymer derived from natural sources. It has been authorized for use in biomedical use because of its uncommon biodegradability, biocompatibility, and mucoadhesive properties. CH modification has been utilized to generate nanoparticles (NPs) for intranasal and intravenous brain targeting. NPs shown upgraded drug take-up to the brain with decreased side impacts due to their drawn out contact time with the nasal mucosa, surface charge, nano size, and capacity to extend the tight intersections inside the mucosa. Due to the aforementioned distinctive characteristics, developing CHNPs load with Bovine Umbilical Mesenchymal Stem Cell Conditioned Medium is crucial as a new therapeutic strategy for canine cognitive dysfunction.

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Section: Search Resultsmentioning

confidence: 99%

Chitosan hydrogel nanoparticle enhance therapeutic effect of bovine umbilical mesenchymal stem cell conditioned medium on canine cognitive dysfunction or canine alzheimer’s like mediated by inhibition of neuronal apoptotic

Wihadmadyatami,

Zulfikar,

Herawati

et al. 2023

Open Vet J

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“…An increasing body of evidence suggests that the Akt/GSK3β/β-catenin signaling pathway is essential in maintaining cell survival after ischemic retinal injury. 48 , 49 Enhanced phosphorylation at serine 473 in Akt reduced the neuronal death of experimental RIR mice, and inhibition of Akt phosphorylation promoted neuronal damage. 50 In the present study, we found that PGB significantly enhanced the phosphorylation of Akt following RIR.…”

Section: Discussionmentioning

confidence: 96%

Pregabalin Mediates Retinal Ganglion Cell Survival From Retinal Ischemia/Reperfusion Injury Via the Akt/GSK3β/β-Catenin Signaling Pathway

Guo

Liu

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose Progressive retinal ganglion cell (RGC) loss induced by retinal ischemia/reperfusion (RIR) injury leads to irreversible visual impairment. Pregabalin (PGB) is a promising drug for neurodegenerative diseases. However, with regard to RGC survival, its specific role and exact mechanism after RIR injury remain unclear. In this study, we sought to investigate whether PGB could protect RGCs from mitochondria-related apoptosis induced by RIR and explore the possible mechanisms. Methods C57BL/6J mice and primary RGCs were pretreated with PGB prior to ischemia/reperfusion modeling. The retinal structure and cell morphology were assessed by immunochemical assays and optical coherence tomography. CCK8 was used to assay cell viability, and an electroretinogram was performed to detect RGC function. Mitochondrial damage was assessed by a reactive oxygen species (ROS) assay kit and transmission electron microscopy. Western blot and immunofluorescence assays quantified the expression of proteins associated with the Akt/GSK3β/β-catenin pathway. Results Treatment with PGB increased the viability of RGCs in vitro. Consistently, PGB preserved the normal thickness of the retina, upregulated Bcl-2, reduced the ratio of cleaved caspase-3/caspase-3 and the expression of Bax in vivo. Meanwhile, PGB improved mitochondrial structure and prevented excessive ROS production. Moreover, PGB restored the amplitudes of oscillatory potentials and photopic negative responses following RIR. The mechanisms underlying its neuroprotective effects were attributed to upregulation of the Akt/GSK3β/β-catenin pathway. However, PGB-mediated neuroprotection was suppressed when using MK2206 (an Akt inhibitor), whereas it was preserved when treated with TWS119 (a GSK3β inhibitor). Conclusions PGB exerts a protective effect against RGC apoptosis induced by RIR injury, mediated by the Akt/GSK3β/β-catenin pathway.

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“…Therefore, in a therapeutic perspective, effective overexpression of such essential neurotrophic factors is the key to curing the disease without causing severe and prolonged pathogenesis. Increased passage of MSCs naturally boost secretion of BDNF; MSCs are promising delivery systems for therapeutics in various neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease, because of their secretomes ( Rodrigues Hell et al, 2009 ; Harrell et al, 2021 ; Jalali et al, 2021 ; Kuo et al, 2021 ). Therefore, BDNF-MSCs could be effective in treating RTT, because of their ability to overexpress BDNF and the presence of neuroprotective or immunomodulatory exosomes.…”

Section: Discussionmentioning

confidence: 99%

Brain-Derived Neurotrophic Factor Secreting Human Mesenchymal Stem Cells Improve Outcomes in Rett Syndrome Mouse Models

et al. 2021

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Rett syndrome (RTT) is a severe X-linked dominant neurodevelopmental disorder caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene; MeCP2 regulates the expression of brain-derived neurotrophic factor (BDNF) and increasing BDNF levels ameliorates RTT symptoms. However, the clinical application of BDNF is limited, because of its short half-life and low penetrance across the blood-brain barrier. In this study, we generated BDNF-secreting mesenchymal stem cells (MSCs) from the human umbilical cord cells, using CRISPR-Cas9. We studied the effects of BDNF-MSCs in MECP2 knockout and MECP2-deficient mice. BDNF-MSCs upregulated the expression of BDNF, pAKT, and pERK1/2 and downregulated that of pp38, both in vitro and in vivo. In our in vivo experiments, BDNF-MSCs increased the body and brain weights in mice. BDNF-MSCs increased the neuronal cell numbers in the hippocampus, cortex, and striatum; in addition, they increased the number of synapses. BDNF-MSCs upregulated BDNF and the activity of BDNF downstream effectors, such as pAKT and pERK 1/2; this upregulation was persistent. In conclusion, BDNF-MSCs generated using CRISPR-Cas9 could be a therapeutic strategy for treating RTT.

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Mesenchymal stem cell‐conditioned medium attenuates the retinal pathology in amyloid‐β‐induced rat model of Alzheimer's disease: Underlying mechanisms

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 17 publications

References 48 publications

Chitosan hydrogel nanoparticle enhance therapeutic effect of bovine umbilical mesenchymal stem cell conditioned medium on canine cognitive dysfunction or canine alzheimer’s like mediated by inhibition of neuronal apoptotic

Chitosan hydrogel nanoparticle enhance therapeutic effect of bovine umbilical mesenchymal stem cell conditioned medium on canine cognitive dysfunction or canine alzheimer’s like mediated by inhibition of neuronal apoptotic

Pregabalin Mediates Retinal Ganglion Cell Survival From Retinal Ischemia/Reperfusion Injury Via the Akt/GSK3β/β-Catenin Signaling Pathway

Brain-Derived Neurotrophic Factor Secreting Human Mesenchymal Stem Cells Improve Outcomes in Rett Syndrome Mouse Models

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