Cellular Therapy in Experimental Autoimmune Encephalomyelitis as an Adjuvant Treatment to Translate for Multiple Sclerosis.

This study aims to evaluate and compare cellular therapy with human Wharton's jelly (WJ) mesenchymal stem cells (MSCs) and neural precursors (NPs) in experimental autoimmune encephalomyelitis (EAE), a preclinical model of Multiple Sclerosis. MSCs were isolated from WJ by an explant technique, differentiated to NPs, and characterized by cytometry and immunocytochemistry analysis after ethical approval. Forty-eight rats were EAE-induced by myelin basic protein and Freund's complete adjuvant. Forty-eight hours later, the animals received intraperitoneal injections of 250 ng/dose of Bordetella pertussis toxin. Fourteen days later, the animals were divided into the following groups: a. non-induced, induced: b. Sham, c. WJ-MSCs, d. NPs, and e. WJ-MSCs plus NPs. 1 × 105. Moreover, the cells were placed in a 10 µL solution and injected via a stereotaxic intracerebral ventricular injection. After ten days, the histopathological analysis for H&E, Luxol, interleukins, and CD4/CD8 was carried out. Statistical analyses demonstrated a higher frequency of clinical manifestation in the Sham group (15.66%) than in the other groups; less demyelination was seen in the treated groups than the Sham group (WJ-MSCs, p = 0.016; NPs, p = 0.010; WJ-MSCs + NPs, p = 0.000), and a lower cellular death rate was seen in the treated groups compared with the Sham group. A CD4/CD8 ratio of <1 showed no association with microglial activation (p = 0.366), astrocytes (p = 0.247), and cell death (p = 0.577) in WJ-MSCs. WJ-MSCs and NPs were immunomodulatory and neuroprotective in cellular therapy, which would be translated as an adjunct in demyelinating diseases.

Meta-analysis of the Mesenchymal Stem Cells Immortalization Protocols: A Guideline for Regenerative Medicine.

BACKGROUND: This systematic review describes the most common methodologies for immortalizing human and animal mesenchymal stem cells (MSCs). This study follows the rules of PRISMA and is registered in the Institutional Review Board of PROSPERO International of systematic reviews, numbered protocol code: CRD42020202465. METHOD: The data search systematization was based on the words "mesenchymal stem cell" AND "immortalization." The search period for publications was between 2000 and 2022, and the databases used were SCOPUS, PUBMED, and SCIENCE DIRECT. The search strategies identified 384 articles: 229 in the SCOPUS database, 84 in PUBMED, and 71 in SCIENCE DIRECT. After screening by titles and abstracts, 285 articles remained. This review included thirty-nine articles according to the inclusion and exclusion criteria. RESULT: In 28 articles, MSCs were immortalized from humans and 11 animals. The most used immortalization methodology was viral transfection. The most common immortalized cell type was the MSC from bone marrow, and the most used gene for immortalizing human and animal MSCs was hTERT (39.3%) and SV40T (54.5%), respectively. CONCLUSION: Also, it was observed that although less than half of the studies performed tumorigenicity assays to validate the immortalized MSCs, other assays, such as qRT-PCR, colony formation in soft agar, karyotype, FISH, and cell proliferation, were performed in most studies on distinct MSC cell passages.

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.