Antisolvent 3D Printing of Gene-Activated Scaffolds for Bone Regeneration.

The use of 3D-printed gene-activated bone grafts represents a highly promising approach in the fields of dentistry and orthopedics. Bioresorbable poly-lactic-co-glycolic acid (PLGA) scaffolds, infused with adenoviral constructs that carry osteoinductive factor genes, may provide an effective alternative to existing bone grafts for the reconstruction of extensive bone defects. This study aims to develop and investigate the properties of 3D scaffolds composed of PLGA and adenoviral constructs carrying the BMP2 gene (Ad-BMP2), both in vitro and in vivo.

Proposed Mechanisms of Cell Therapy for Alzheimer's Disease.

Alzheimer's disease is a progressive neurodegenerative disorder characterized by mitochondria dysfunction, accumulation of beta-amyloid plaques, and hyperphosphorylated tau tangles in the brain leading to memory loss and cognitive deficits. There is currently no cure for this condition, but the potential of stem cells for the therapy of neurodegenerative pathologies is actively being researched. This review discusses preclinical and clinical studies that have used mouse models and human patients to investigate the use of novel types of stem cell treatment approaches.

Collagen-Platelet-Rich Plasma Mixed Hydrogels as a pBMP2 Delivery System for Bone Defect Regeneration.

The replenishment of bone deficiency remains a challenging task in clinical practice. The use of gene-activated matrices (GAMs) impregnated with genetic constructs may be an innovative approach to solving this problem. The aim of this work is to develop collagen-based matrices with the addition of platelet-rich plasma, carrying polyplexes with the gene, to study their biocompatibility and osteogenic potential in vitro and in vivo.

Estimation of Chloride Channel Residual Function and Assessment of Targeted Drugs Efficiency in the Presence of a Complex Allele [L467F;F508del] in the Gene.

Complex alleles of the gene complicate the diagnosis of cystic fibrosis (CF), the classification of its pathogenic variants, affect the clinical picture of the disease and can affect the efficiency of targeted drugs. The total frequency of complex allele [L467F;F508del] in the Russian population of patients with CF is 0.74%, and in patients with the F508del/F508del genotype, its frequency reaches 8%.

Oral Microbiome Dysbiosis as a Risk Factor for Stroke: A Comprehensive Review.

Stroke represents a significant global health burden, with a substantial impact on mortality, morbidity, and long-term disability. The examination of stroke biomarkers, particularly the oral microbiome, offers a promising avenue for advancing our understanding of the factors that contribute to stroke risk and for developing strategies to mitigate that risk. This review highlights the significant correlations between oral diseases, such as periodontitis and caries, and the onset of stroke.

Application of BMP-2 and its gene delivery vehicles in dentistry.

The restoration of bone defects resulting from tooth loss, periodontal disease, severe trauma, tumour resection and congenital malformations is a crucial task in dentistry and maxillofacial surgery. Growth factor- and gene-activated bone graft substitutes can be used instead of traditional materials to solve these problems. New materials will overcome the low efficacy and difficulties associated with the use of traditional bone substitutes in complex situations.

Airway basal cells from human-induced pluripotent stem cells: a new frontier in cystic fibrosis research.

Human-induced airway basal cells (hiBCs) derived from human-induced pluripotent stem cells (hiPSCs) offer a promising cell model for studying lung diseases, regenerative medicine, and developing new gene therapy methods. We analyzed existing differentiation protocols and proposed our own protocol for obtaining hiBCs, which involves step-by-step differentiation of hiPSCs into definitive endoderm, anterior foregut endoderm, NKX2.1+ lung progenitors, and cultivation on basal cell medium with subsequent cell sorting using the surface marker CD271 (NGFR).

Comprehensive Assessment of Modulators' Therapeutic Efficiency for N1303K Variant.

p.Asn1303Lys (N1303K) is a common missense variant of the gene, causing cystic fibrosis (CF). In this study, we initially evaluated the influence of modulators on the restoration of N1303K- function using intestinal organoids derived from four CF patients expressing the N1303K variant.

Advances in the Study of Common and Rare Complex Alleles Using Intestinal Organoids.

Complex alleles (CAs) arise when two or more nucleotide variants are present on a single allele. CAs of the gene complicate the cystic fibrosis diagnosis process, classification of pathogenic variants, and determination of the clinical picture of the disease and increase the need for additional studies to determine their pathogenicity and modulatory effect in response to targeted therapy. For several different populations around the world, characteristic CAs of the gene have been discovered, although in general the prevalence and pathogenicity of CAs have not been sufficiently studied.

The Effect of Complex Alleles of the Gene on the Clinical Manifestations of Cystic Fibrosis and the Effectiveness of Targeted Therapy.

The authors of this article analyzed the available literature with the results of studying the prevalence of complex alleles of the gene among patients with cystic fibrosis, and their pathogenicity and influence on targeted therapy with CFTR modulators. Cystic fibrosis (CF) is a multisystemic autosomal recessive disease caused by a defect in the expression of the CFTR protein, and more than 2000 genetic variants are known. Clinically significant variants are divided into seven classes.

Comparative Study of the Protective and Neurotrophic Effects of Neuronal and Glial Progenitor Cells-Derived Conditioned Media in a Model of Glutamate Toxicity In Vitro.

Cell therapy represents a promising approach to the treatment of neurological diseases, offering potential benefits not only by cell replacement but also through paracrine secretory activities. However, this approach includes a number of limiting factors, primarily related to safety. The use of conditioned stem cell media can serve as an equivalent to cell therapy while avoiding its disadvantages.

Comparative study of the efficacy of intra-arterial and intravenous transplantation of human induced pluripotent stem cells-derived neural progenitor cells in experimental stroke.

Background: Cell therapy using neural progenitor cells (NPCs) is a promising approach for ischemic stroke treatment according to the results of multiple preclinical studies in animal stroke models. In the vast majority of conducted animal studies, the therapeutic efficacy of NPCs was estimated after intracerebral transplantation, while the information of the effectiveness of systemic administration is limited. Nowadays, several clinical trials aimed to estimate the safety and efficacy of NPCs transplantation in stroke patients were also conducted.

Extracellular vesicles of human glial cells exert neuroprotective effects via brain miRNA modulation in a rat model of traumatic brain injury.

Stem cell-based therapeutic approaches for neurological disorders are widely studied. Paracrine factors secreted by stem cells in vitro and delivered intranasally might allow bypassing the disadvantages associated with a surgical cell delivery procedure with likely immune rejection of a transplant. In this study, we investigated the therapeutic effect of the extracellular vesicles secreted by glial progenitor cells (GPC-EV) derived from human induced pluripotent stem cell in a traumatic brain injury model.

Clinical and Genetic Characteristics of a Patient with Cystic Fibrosis with a Complex Allele [E217G;G509D] and Functional Evaluation of the CFTR Channel.

The intricate nature of complex alleles presents challenges in the classification of gene mutations, encompassing potential disease-causing, neutral, or treatment-modulating effects. Notably, the complex allele [E217G;G509D] remains absent from international databases, with its pathogenicity yet to be established. Assessing the functionality of apical membrane ion channels in intestinal epithelium employed the intestinal current measurements (ICM) method, using rectal biopsy material.

Therapeutic Efficiency of Proteins Secreted by Glial Progenitor Cells in a Rat Model of Traumatic Brain Injury.

Traumatic brain injuries account for 30-50% of all physical traumas and are the most common pathological diseases of the brain. Mechanical damage of brain tissue leads to the disruption of the blood-brain barrier and the massive death of neuronal, glial, and endothelial cells. These events trigger a neuroinflammatory response and neurodegenerative processes locally and in distant parts of the brain and promote cognitive impairment.

Adenovirus-Based Gene Therapy for Bone Regeneration: A Comparative Analysis of In Vivo and Ex Vivo Gene Delivery.

Adenovirus-mediated gene therapy is a promising tool in bone regenerative medicine. In this work, gene-activated matrices (GAMs) composed of (1) polylactide granules (PLA), which serve as a depot for genetic constructs or matrices for cell attachment, (2) a PRP-based fibrin clot, which is a source of growth factors and a binding gel, and (3) a gene providing osteoinductive properties were studied. The study aims to compare the effectiveness of in vivo and ex vivo gene therapy based on adenoviral constructs with the gene, PLA particles, and a fibrin clot for bone defect healing.

Osteogenesis Enhancement with 3D Printed Gene-Activated Sodium Alginate Scaffolds.

Natural and synthetic hydrogel scaffolds containing bioactive components are increasingly used in solving various tissue engineering problems. The encapsulation of DNA-encoding osteogenic growth factors with transfecting agents (e.g.

Clinical and Functional Characteristics of the E92K Gene Variant in the Russian and Turkish Population of People with Cystic Fibrosis.

The pathogenic variant E92K (c.274G > A) of the gene is rare in America and Europe, but it is common for people with cystic fibrosis from Russia and Turkey. We studied the effect of the E92K genetic variant on the CFTR function.

Airway and Lung Organoids from Human-Induced Pluripotent Stem Cells Can Be Used to Assess CFTR Conductance.

Airway and lung organoids derived from human-induced pluripotent stem cells (hiPSCs) are current models for personalized drug screening, cell-cell interaction studies, and lung disease research. We analyzed the existing differentiation protocols and identified the optimal conditions for obtaining organoids. In this article, we describe a step-by-step protocol for differentiating hiPSCs into airway and lung organoids.

Spleen regeneration after subcutaneous heterotopic autotransplantation in a mouse model.

Background: Splenectomy may lead to severe postoperative complications, including sepsis and cancers. A possible solution to this problem is heterotopic autotransplantation of the spleen. Splenic autografts rapidly restore the regular splenic microanatomy in model animals.

Comparative Efficiency of Gene-Activated Matrices Based on Chitosan Hydrogel and PRP Impregnated with Polyplexes for Bone Regeneration.

Gene therapy is one of the most promising approaches in regenerative medicine. Gene-activated matrices provide stable gene expression and the production of osteogenic proteins in situ to stimulate osteogenesis and bone repair. In this study, we developed new gene-activated matrices based on polylactide granules (PLA) impregnated with polyplexes and included in chitosan hydrogel or PRP-based fibrin hydrogel.

Personalized Selection of a CFTR Modulator for a Patient with a Complex Allele [L467F;F508del].

The presence of complex alleles in the CFTR gene can lead to difficulties in diagnosing cystic fibrosis and cause resistance to therapy with CFTR modulators. Tezacaftor/ivacaftor therapy for 8 months in a patient with the initially established F508del/F508del genotype did not lead to an improvement in her condition-there was no change in spirometry and an increase in the patient's weight, while there was only a slight decrease in NaCl values, measured by a sweat test. The intestinal current measurements of the patient's rectal biopsy showed no positive dynamics in the rescue of CFTR function while taking tezacaftor/ivacaftor.

Evaluation of the Complex p.[Leu467Phe;Phe508del] CFTR Allele in the Intestinal Organoids Model: Implications for Therapy.

In the cohort of Russian patients with cystic fibrosis, the p.[Leu467Phe;Phe508del] complex allele (legacy name [L467F;F508del]) of the CFTR gene is understudied. In this research, we present the results of frequency evaluation of the [L467F;F508del] complex allele in the Russian Federation among patients with a F508del/F508del genotype, its effect on the clinical course of cystic fibrosis, the intestinal epithelium ionic channel function, and the effectiveness of target therapy.

3D Printed Gene-Activated Sodium Alginate Hydrogel Scaffolds.

Gene therapy is one of the most promising approaches in regenerative medicine to restore damaged tissues of various types. However, the ability to control the dose of bioactive molecules in the injection site can be challenging. The combination of genetic constructs, bioresorbable material, and the 3D printing technique can help to overcome these difficulties and not only serve as a microenvironment for cell infiltration but also provide localized gene release in a more sustainable way to induce effective cell differentiation.