Next-generation treatments: Immunotherapy and advanced therapies for COVID-19.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in 2019 following prior outbreaks of coronaviruses like SARS and MERS in recent decades, underscoring their high potential of infectivity in humans. Insights from previous outbreaks of SARS and MERS have played a significant role in developing effective strategies to mitigate the global impact of SARS-CoV-2. As of January 7, 2024, there have been 774,075,242 confirmed cases of COVID-19 worldwide. To date, 13.59 billion vaccine doses have been administered, and there have been 7,012,986 documented fatalities (https://www.who.int/) Despite significant progress in addressing the COVID-19 pandemic, the rapid evolution of SARS-CoV-2 challenges human defenses, presenting ongoing global challenges. The emergence of new SARS-CoV-2 lineages, shaped by mutation and recombination processes, has led to successive waves of infections. This scenario reveals the need for next-generation vaccines as a crucial requirement for ensuring ongoing protection against SARS-CoV-2. This demand calls for formulations that trigger a robust adaptive immune response without leading the acute inflammation linked with the infection. Key mutations detected in the Spike protein, a critical target for neutralizing antibodies and vaccine design -specifically within the Receptor Binding Domain region of Omicron variant lineages (B.1.1.529), currently dominant worldwide, have intensified concerns due to their association with immunity evasion from prior vaccinations and infections. As the world deals with this evolving threat, the narrative extends to the realm of emerging variants, each displaying new mutations with implications that remain largely misunderstood. Notably, the JN.1 Omicron lineage is gaining global prevalence, and early findings suggest it stands among the immune-evading variants, a characteristic attributed to its mutation L455S. Moreover, the detrimental consequences of the novel emergence of SARS-CoV-2 lineages bear a particularly critical impact on immunocompromised individuals and older adults. Immunocompromised individuals face challenges such as suboptimal responses to COVID-19 vaccines, rendering them more susceptible to severe disease. Similarly, older adults have an increased risk of severe disease and the presence of comorbid conditions, find themselves at a heightened vulnerability to develop COVID-19 disease. Thus, recognizing these intricate factors is crucial for effectively tailoring public health strategies to protect these vulnerable populations. In this context, this review aims to describe, analyze, and discuss the current progress of the next-generation treatments encompassing immunotherapeutic approaches and advanced therapies emerging as complements that will offer solutions to counter the disadvantages of the existing options. Preliminary outcomes show that these strategies target the virus and address the immunomodulatory responses associated with COVID-19. Furthermore, the capacity to promote tissue repair has been demonstrated, which can be particularly noteworthy for immunocompromised individuals who stand as vulnerable actors in the global landscape of coronavirus infections. The emerging next-generation treatments possess broader potential, offering protection against a wide range of variants and enhancing the ability to counter the impact of the constant evolution of the virus. Furthermore, advanced therapies are projected as potential treatment alternatives for managing Chronic Post-COVID-19 syndromeand addressing its associated long-term complications.

Evidence of Extracellular Vesicles Biogenesis and Release in Mouse Embryonic Stem Cells.

Extracellular vesicles (EVs) released by mouse embryonic stem cells (mESCs) are considered a source of bioactive molecules that modulate their microenvironment by acting on intercellular communication. Either intracellular endosomal machinery or their derived EVs have been considered a relevant system of signal circuits processing. Herein, we show that these features are found in mESCs. Ultrastructural analysis revealed structures and organelles of the endosomal system such as coated pits and endocytosis-related vesicles, prominent rough endoplasmic reticulum and Golgi apparatus, and multivesicular bodies (MVBs) containing either few or many intraluminal vesicles (ILVs) that could be released as exosomes to extracellular milieu. Besides, budding vesicles shed from the plasma membrane to the extracellular space is suggestive of microvesicle biogenesis in mESCs. mESCs and mouse blastocyst express specific markers of the Endosomal Sorting Complex Required for Transport (ESCRT) system. Ultrastructural analysis and Nanoparticle Tracking Analysis (NTA) of isolated EVs revealed a heterogeneous population of exosomes and microvesicles released by mESCs. These vesicles contain Wnt10b and the Notch ligand Delta-like 4 (DLL4) and also the co-chaperone stress inducible protein 1 (STI1) and its partner Hsp90. Wnt10b and Dll4 colocalize with EVs biogenesis markers in mESCs. Overall, the present study supports the function of the mESCs endocytic network and their EVs as players in stem cell biology.

Células madre mesenquimales: características biológicas y aplicaciones clínicas / Mesenchymal stem cells: Biological characteristics and clinical applications

Las células madre mesenquimales son células pluripotentes y adultas con morfología fibroblastoide y plasticidad hacia diversos linajes celulares como condrocitos, osteocitos y adipocitos entre otros. Estas células pueden ser aisladas principalmente de médula ósea, sangre de cordón umbilical y tejido adiposo de donde se han logrado establecer cultivos que han permitido estudiar sus propiedades funcionales y fenotípicas. Aunque la información obtenida hasta la fecha no brinda un conocimiento completo, se espera que con el desarrollo de próximas investigaciones se aclaren diversos aspectos biológicos para implementar su uso en medicina regenerativa. Esta revisión presenta una visión general sobre las células madre mesenquimales: morfología e inmunofenotipo, ontogenia, fuentes de obtención y aplicaciones clínicas.