State of the Art of microRNAs Signatures as Biomarkers and Therapeutic Targets in Parkinson's and Alzheimer's Diseases: A Systematic Review and Meta-Analysis.

Identifying target microRNAs (miRNAs) might serve as a basis for developing advanced therapies for Parkinson's disease (PD) and Alzheimer's disease. This review aims to identify the main therapeutic targets of miRNAs that can potentially act in Parkinson's and Alzheimer's diseases. The publication research was conducted from May 2021 to March 2022, selected from Scopus, PubMed, Embase, OVID, Science Direct, LILACS, and EBSCO. A total of 25 studies were selected from 1549 studies evaluated. The total number of miRNAs as therapeutic targets evidenced was 90 for AD and 54 for PD. An average detection accuracy of above 84% for the miRNAs was observed in the selected studies of AD and PD. The major signatures were miR-26b-5p, miR-615-3p, miR-4722-5p, miR23a-3p, and miR-27b-3p for AD and miR-374a-5p for PD. Six miRNAs of intersection were found between AD and PD. This article identified the main microRNAs as selective biomarkers for diagnosing PD and AD and therapeutic targets through a systematic review and meta-analysis. This article can act as a microRNA guideline for laboratory research and pharmaceutical industries for treating Alzheimer's and Parkinson's diseases and offers the opportunity to evaluate therapeutic interventions earlier in the disease process.

Three-Dimensional Bioprinting of an In Vitro Lung Model.

In December 2019, COVID-19 emerged in China, and in January 2020, the World Health Organization declared a state of international emergency. Within this context, there is a significant search for new drugs to fight the disease and a need for in vitro models for preclinical drug tests. This study aims to develop a 3D lung model. For the execution, Wharton's jelly mesenchymal stem cells (WJ-MSC) were isolated and characterized through flow cytometry and trilineage differentiation. For pulmonary differentiation, the cells were seeded in plates coated with natural functional biopolymer matrix as membrane until spheroid formation, and then the spheroids were cultured with differentiation inductors. The differentiated cells were characterized using immunocytochemistry and RT-PCR, confirming the presence of alveolar type I and II, ciliated, and goblet cells. Then, 3D bioprinting was performed with a sodium alginate and gelatin bioink in an extrusion-based 3D printer. The 3D structure was analyzed, confirming cell viability with a live/dead assay and the expression of lung markers with immunocytochemistry. The results showed that the differentiation of WJ-MSC into lung cells was successful, as well as the bioprinting of these cells in a 3D structure, a promising alternative for in vitro drug testing.

The Neural Multilineage Differentiation Capacity of Human Neural Precursors from the Umbilical Cord-Ready to Bench for Clinical Trials.

Mesenchymal stem cells (MSC) are promising for regenerative medicine as they have a vast differentiation capacity, immunomodulatory properties and can be isolated from different tissues. Among them, the umbilical cord is considered a good source of MSC, as its collection poses no risk to donors and is unrelated to ethical issues. Furthermore, umbilical cord mesenchymal stem cells (UC-MSC) can differentiate into several cell lines, including neural lineages that, in the future, may become an alternative in the treatment of neurodegenerative diseases. This study used a natural functional biopolymer matrix (NFBX) as a membrane to differentiate UC-MSC into neurospheres and their Neural precursors without using neurogenic growth factors or gene transfection. Through the characterization of Neural precursors and differentiated cells, it was possible to demonstrate the broad potential for the differentiation of cells obtained through cultivation on this membrane. To demonstrate these Neural precursors' potential for future studies in neurodegenerative diseases, the Neural precursors from Wharton's jelly were differentiated into Schwann cells, oligodendrocytes, cholinergic-, dopaminergic- and GABAergic-like neurons.

Biodegradable Nanoparticles Loaded with Levodopa and Curcumin for Treatment of Parkinson's Disease.

Background: Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder. Levodopa (L-DOPA) remains the gold-standard drug available for treating PD. Curcumin has many pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anti-amyloid, and antitumor properties. Copolymers composed of Poly (ethylene oxide) (PEO) and biodegradable polyesters such as Poly (ε-caprolactone) (PCL) can self-assemble into nanoparticles (NPs). This study describes the development of NH2-PEO-PCL diblock copolymer positively charged and modified by adding glutathione (GSH) on the outer surface, resulting in a synergistic delivery of L-DOPA curcumin that would be able to pass the blood-brain barrier. Methods: The NH2-PEO-PCL NPs suspensions were prepared by using a nanoprecipitation and solvent displacement method and coated with GSH. NPs were submitted to characterization assays. In order to ensure the bioavailability, Vero and PC12 cells were treated with various concentrations of the loaded and unloaded NPs to observe cytotoxicity. Results: NPs have successfully loaded L-DOPA and curcumin and were stable after freeze-drying, indicating advancing into in vitro toxicity testing. Vero and PC12 cells that were treated up to 72 h with various concentrations of L-DOPA and curcumin-loaded NP maintained high viability percentage, indicating that the NPs are biocompatible. Conclusions: NPs consisting of NH2-PEO-PCL were characterized as potential formulations for brain delivery of L-DOPA and curcumin. The results also indicate that the developed biodegradable nanomicelles that were blood compatible presented low cytotoxicity.

Tracheal Repair with Human Umbilical Cord Mesenchymal Stem Cells Differentiated in Chondrocytes Grown on an Acellular Amniotic Membrane: A Pre-Clinical Approach.

Acellular amniotic membrane (AM) has been studied, with promising results on the reconstruction of lesioned tissues, and has become an attractive approach for tracheal repair. This study aimed to evaluate the repair of the trachea with human umbilical cord mesenchymal stem cells (hucMSCs) differentiated in chondrocytes, grown on an experimental model. Tracheal defects were induced by surgical tracheostomy in 30 New Zealand rabbits, and the acellular amniotic membrane, with or without cells, was covering the defect. The hucMSCs were isolated and cultivated with chondrogenic differentiation over the culture of 14 days, and then grown on the AM. In this study, the AM was biocompatible and hucMSCs differentiated into chondrocytes. Our results demonstrated an important role for AM with cultured cells in the promotion of immature collagen, known to produce tissue regeneration. In addition, cartilaginous tissue was found at the tracheal defects, demonstrated by immunohistology results. This study suggests that this biomaterial implantation can be an effective future therapeutic alternative for patients with tracheal injury.

Natural Membrane Differentiates Human Adipose-Derived Mesenchymal Stem Cells to Neurospheres by Mechanotransduction Related to YAP and AMOT Proteins.

Adipose tissue-derived mesenchymal stem cells (ADMSCs) are promising candidates for regenerative medicine, as they have good cell yield and can differentiate into several cell lines. When induced to the neuronal differentiation, they form neurospheres composed of neural precursors (NPs) that can be an alternative in treating neurodegenerative diseases. This study aimed to characterize NPs from neurospheres obtained after seeding ADMSCs on a natural polyisoprene-based membrane. The ADMSCs were isolated from adipose tissue by enzymatic dissociation, were subjected to trilineage differentiation, and were characterized by flow cytometry for specific ADMSC surface markers. For neuronal differentiation, the cells were seeded on polystyrene flasks coated with the membrane and were characterized by immunocytochemistry and RT-PCR. The results demonstrated that the isolated cells showed characteristics of ADMSCs. At 15 to 25 days, ADMSCs seeded on the natural membrane developed neurospheres. Then, after dissociation, the cells demonstrated characteristic neuronal markers expressed on NPs: nestin, ß-III tubulin, GFAP, NeuN, and the YAP1/AMOT in the cytoplasm. In conclusion, it was demonstrated that this membrane differentiates the ADMSCs to NPs without any induction factors, and suggests that their differentiation mechanisms are related to mechanotransduction regulated by the YAP and AMOT proteins.

Beneficial Roles of Cellulose Patch-Mediated Cell Therapy in Myocardial Infarction: A Preclinical Study.

Biological scaffolds have become an attractive approach for repairing the infarcted myocardium and have been shown to facilitate constructive remodeling in injured tissues. This study aimed to investigate the possible utilization of bacterial cellulose (BC) membrane patches containing cocultured cells to limit myocardial postinfarction pathology. Myocardial infarction (MI) was induced by ligating the left anterior descending coronary artery in 45 Wistar rats, and patches with or without cells were attached to the hearts. After one week, the animals underwent echocardiography to assess for ejection fraction and left ventricular end-diastolic and end-systolic volumes. Following patch formation, the cocultured cells retained viability of >90% over 14 days in culture. The patch was applied to the myocardial surface of the infarcted area after staying 14 days in culture. Interestingly, the BC membrane without cellular treatment showed higher preservation of cardiac dimensions; however, we did not observe improvement in the left ventricular ejection fraction of this group compared to coculture-treated membranes. Our results demonstrated an important role for BC in supporting cells known to produce cardioprotective soluble factors and may thus provide effective future therapeutic outcomes for patients suffering from ischemic heart disease.