Deciphering the impact of cerebrospinal fluid on stem cell fate as a new mechanism to enhance clinical therapy development.

Neural stem cells (NSCs) hold a very significant promise as candidates for cell therapy due to their robust neuroprotective and regenerative properties. Preclinical studies using NSCs have shown enough encouraging results to perform deeper investigations into more potential clinical applications. Nevertheless, our knowledge regarding neurogenesis and its underlying mechanisms remains incomplete. To understand them better, it seems necessary to characterize all components of neural stem cell niche and discover their role in physiology and pathology. Using NSCs in vivo brings challenges including limited cell survival and still inadequate integration within host tissue. Identifying overlooked factors that might influence these outcomes becomes pivotal. In this review, we take a deeper examination of the influence of a fundamental element that is present in the brain, the cerebrospinal fluid (CSF), which still remains relatively unexplored. Its role in neurogenesis could be instrumental to help find novel therapeutic solutions for neurological disorders, eventually advancing our knowledge on central nervous system (CNS) regeneration and repair.

Should We Consider Them as a Threat? Antimicrobial Resistance, Virulence Potential and Genetic Diversity of Campylobacter spp. Isolated from Varsovian Dogs.

Campylobacteriosis seems to be a growing problem worldwide. Apart from the most common sources of numerous Campylobacter species, such as poultry and other farm animals, dogs may be an underrated reservoir of this pathogen. Our goal was to establish the frequency of occurrence, antimicrobial resistance, and detection of chosen virulence factor genes in genomes of canine Campylobacter isolates. Campylobacter isolates frequency in dogs from shelters, and private origin was 13%. All of the tested virulence factor genes were found in 28 of 31 isolates. We determined high resistance levels to the ciprofloxacin and ampicillin and moderate tetracycline resistance. For C. jejuni shelter isolates, genetic diversity was also determined using PFGE. Our results indicate that dogs may be the reservoir of potentially diverse, potentially virulent, and antimicrobial-resistant Campylobacter strains.

Critical factors responsible for the therapeutic effect of mesenchymal stem/stromal cells in central nervous system disorders.

Nowadays it is observed that the number of stem-cell based experimental therapies in neurodegenerative disorders is massively increasing. Most of the clinical trials registered to date have been based on autologous mesenchymal stem/stromal cells (MSC) obtained from somatic tissues. In the conducted clinical trials neither serious side effects, nor statistically significant improvement were observed. The lack of statistical significance could result from a relatively small number of patients involved in clinical trials or highly incoherent study protocols. However, most clinical groups describe a trend towards improvement in MSC-treated patients. Hence, the question arises which factors associated with MSC-based therapy may be the key and result in better therapeutic response. In the presented paper, we summarize, in our opinion, the most important factors that could increase the effectiveness of this therapy.

Evaluation of the Optimal Manufacturing Protocols and Therapeutic Properties of Mesenchymal Stem/Stromal Cells Derived from Wharton's Jelly.

Wharton's jelly (WJ) from the umbilical cord (UC) is a good source of mesenchymal stem/stromal cells (MSCs), which can be isolated and used in therapy. Current knowledge shows that even small changes in the cell environment may result in obtaining a subpopulation of cells with different therapeutic properties. For this reason, the conditions of UC transportation, cell isolation, and cultivation and the banking of cells destined for clinical use should be unified and optimized. In this project, we tried various protocols for cell vs. bioptat isolation, banking, and transport in order to determine the most optimal. The most efficient isolation method of WJ-MSCs was chopping the whole umbilical matrix with a scalpel after vessel and lining membrane removal. The optimal solution for short term cell transportation was a multi-electrolyte fluid without glucose. Considering the use of WJ-MSCs in cell therapies, it was important to investigate the soluble secretome of both WJ bioptats and WJ-MSCs. WJ-MSCs secreted higher levels of cytokines and chemokines than WJ bioptats. WJ-MSCs secreted HGF, CCL2, ICAM-1, BDNF, and VEGF. Since these cells might be used in treating neurodegenerative disorders, we investigated the impact of cerebrospinal fluid (CSF) on WJ-MSCs' features. In the presence of CSF, the cells expressed consecutive neural markers both at the protein and gene level: nestin, ß-III-tubulin, S-100-ß, GFAP, and doublecortin. Based on the obtained results, a protocol for manufacturing an advanced-therapy medicinal product was composed.