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1.
Int J Mol Sci ; 25(13)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-39000479

RESUMO

It has been widely established that the characterization of extracellular vesicles (EVs), particularly small EVs (sEVs), shed by different cell types into biofluids, helps to identify biomarkers and therapeutic targets in neurological and neurodegenerative diseases. Recent studies are also exploring the efficacy of mesenchymal stem cell-derived extracellular vesicles naturally enriched with therapeutic microRNAs and proteins for treating various diseases. In addition, EVs released by various neural cells play a crucial function in the modulation of signal transmission in the brain in physiological conditions. However, in pathological conditions, such EVs can facilitate the spread of pathological proteins from one brain region to the other. On the other hand, the analysis of EVs in biofluids can identify sensitive biomarkers for diagnosis, prognosis, and disease progression. This review discusses the potential therapeutic use of stem cell-derived EVs in several central nervous system diseases. It lists their differences and similarities and confers various studies exploring EVs as biomarkers. Further advances in EV research in the coming years will likely lead to the routine use of EVs in therapeutic settings.


Assuntos
Biomarcadores , Doenças do Sistema Nervoso Central , Vesículas Extracelulares , Humanos , Vesículas Extracelulares/metabolismo , Doenças do Sistema Nervoso Central/metabolismo , Doenças do Sistema Nervoso Central/terapia , Doenças do Sistema Nervoso Central/diagnóstico , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Células-Tronco Mesenquimais/metabolismo , Doenças Neurodegenerativas/terapia , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/diagnóstico
2.
Cells ; 13(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38727281

RESUMO

This review delves into the groundbreaking impact of induced pluripotent stem cells (iPSCs) and three-dimensional organoid models in propelling forward neuropathology research. With a focus on neurodegenerative diseases, neuromotor disorders, and related conditions, iPSCs provide a platform for personalized disease modeling, holding significant potential for regenerative therapy and drug discovery. The adaptability of iPSCs, along with associated methodologies, enables the generation of various types of neural cell differentiations and their integration into three-dimensional organoid models, effectively replicating complex tissue structures in vitro. Key advancements in organoid and iPSC generation protocols, alongside the careful selection of donor cell types, are emphasized as critical steps in harnessing these technologies to mitigate tumorigenic risks and other hurdles. Encouragingly, iPSCs show promising outcomes in regenerative therapies, as evidenced by their successful application in animal models.


Assuntos
Células-Tronco Pluripotentes Induzidas , Organoides , Organoides/patologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Animais , Neuropatologia/métodos , Medicina Regenerativa/métodos , Doenças Neurodegenerativas/terapia , Doenças Neurodegenerativas/patologia , Diferenciação Celular
3.
Biology (Basel) ; 13(5)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38785785

RESUMO

Stress is an important risk factor for the onset of anxiety and depression. The ability to cope with stressful events varies among different subjects, probably depending on different genetic variants, sex and previous life experiences. The Val66Met variant of Brain-Derived Neurotrophic Factor (BDNF), which impairs the activity-dependent secretion of BDNF, has been associated with increased susceptibility to the development of various neuropsychiatric disorders. Adult male and female wild-type Val/Val (BDNFV/V) and heterozygous Val/Met (BDNFV/M) mice were exposed to two sessions of forced swimming stress (FSS) per day for two consecutive days. The mice were behaviorally tested 1 day (short-term effect) or 11 days (long-term effect) after the last stress session. Protein and mRNA levels were measured in the hippocampus 16 days after the end of stress exposure. Stressed mice showed a higher anxiety-like phenotype compared to non-stressed mice, regardless of the sex and genotype, when analyzed following the short period of stress. In the prolonged period, anxiety-like behavior persisted only in male BDNFV/M mice (p < 0.0001). Interestingly, recovery in male BDNFV/V mice was accompanied by an increase in pCREB (p < 0.001) and Bdnf4 (p < 0.01) transcript and a decrease in HDAC1 (p < 0.05) and Dnmt3a (p = 0.01) in the hippocampus. Overall, our results show that male and female BDNF Val66Met knock-in mice can recover from subchronic stress in different ways.

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