Exosome-loaded decellularized tissue: Opening a new window for regenerative medicine.

Mesenchymal stem cell-derived exosomes (MSCs-EXO) have received a lot of interest recently as a potential therapeutic tool in regenerative medicine. Extracellular vesicles (EVs) known as exosomes (EXOs) are crucial for cell-cell communication throughout a variety of activities including stress response, aging, angiogenesis, and cell differentiation. Exploration of the potential use of EXOs as essential therapeutic effectors of MSCs to encourage tissue regeneration was motivated by success in the field of regenerative medicine. EXOs have been administered to target tissues using a variety of methods, including direct, intravenous, intraperitoneal injection, oral delivery, and hydrogel-based encapsulation, in various disease models. Despite the significant advances in EXO therapy, various methods are still being researched to optimize the therapeutic applications of these nanoparticles, and it is not completely clear which approach to EXO administration will have the greatest effects. Here, we will review emerging developments in the applications of EXOs loaded into decellularized tissues as therapeutic agents for use in regenerative medicine in various tissues.

Central Nervous System Delivery of Antibodies and Their Single-Domain Antibodies and Variable Fragment Derivatives with Focus on Intranasal Nose to Brain Administration.

IgG antibodies are some of the most important biopharmaceutical molecules with a high market volume. In spite of the fact that clinical therapies with antibodies are broadly utilized in oncology, immunology and hematology, their delivery strategies and biodistribution need improvement, their limitations being due to their size and poor ability to penetrate into tissues. In view of their small size, there is a rising interest in derivatives, such as single-domain antibodies and single-chain variable fragments, for clinical diagnostic but also therapeutic applications. Smaller antibody formats combine several benefits for clinical applications and can be manufactured at reduced production costs compared with full-length IgGs. Moreover, such formats have a relevant potential for targeted drug delivery that directs drug cargo to a specific tissue or across the blood-brain barrier. In this review, we give an overview of the challenges for antibody drug delivery in general and focus on intranasal delivery to the central nervous system with antibody formats of different sizes.

Selective CNS Targeting and Distribution with a Refined Region-Specific Intranasal Delivery Technique via the Olfactory Mucosa.

Intranasal drug delivery is a promising approach for the delivery of drugs to the CNS, but too heterogenous, unprecise delivery methods without standardization decrease the quality of many studies in rodents. Thus, the lack of a precise and region-specific application technique for mice is a major drawback. In this study, a previously developed catheter-based refined technique was validated against the conventional pipette-based method and used to specifically reach the olfactory or the respiratory nasal regions. This study successfully demonstrated region-specific administration at the olfactory mucosa resulting in over 20% of the administered fluorescein dose in the olfactory bulbs, and no peripheral bioactivity of insulin detemir and Fc-dependent uptake of two murine IgG1 (11C7 and P3X) along the olfactory pathway to cortex and hippocampus. An scFv of 11C7 showed hardly any uptake to the CNS. Elimination was dependent on the presence of the IgG's antigen. In summary, it was successfully demonstrated that region-specific intranasal administration via the olfactory region resulted in improved brain targeting and reduced peripheral targeting in mice. The data are discussed with regard to their clinical potential.

Mesenchymal stem cell (MSC)-derived exosomes as a cell-free therapy for patients Infected with COVID-19: Real opportunities and range of promises.

There are no commercially available effective antiviral medications or vaccines to deal with novel coronavirus disease (COVID-19). Hence there is a substantial unmet medical need for new and efficacious treatment options for COVID-19. Most COVID-19 deaths result from acute respiratory distress syndrome (ARDS). This virus induces excessive and aberrant inflammation so it is important to control the inflammation as soon as possible. To date, results of numerous studies have been shown that mesenchymal stem cells and their derivatives can suppress inflammation. Exosomes function as intercellular communication vehicles to transfer bioactive molecules (based on their origins), between cells. In this review, the recent exosome-based clinical trials for the treatment of COVID-19 are presented. Potential therapy may include the following items: First, using mesenchymal stem cells secretome. Second, incorporating specific miRNAs and mRNAs into exosomes and last, using exosomes as carriers to deliver drugs.