Nejvíce citovaný článek - PubMed ID 25529339
COVID-19, a significant global health threat, appears to be an immune-related disease. Failure of effective immune responses in initial stages of infection may contribute to development of cytokine storm and systemic inflammation with organ damage, leading to poor clinical outcomes. Disease severity and the emergence of new SARS-CoV-2 variants highlight the need for new preventative and therapeutic strategies to protect the immunocompromised population. Available data indicate that these people may benefit from adoptive transfer of allogeneic SARS-CoV-2-specific T cells isolated from convalescent individuals. This review first provides an insight into the mechanism of cytokine storm development, as it is directly related to the exhaustion of T cell population, essential for viral clearance and long-term antiviral immunity. Next, we describe virus-specific T lymphocytes as a promising and efficient approach for the treatment and prevention of severe COVID-19. Furthermore, other potential cell-based therapies, including natural killer cells, regulatory T cells and mesenchymal stem cells are mentioned. Additionally, we discuss fast and effective ways of producing clinical-grade antigen-specific T cells which can be cryopreserved and serve as an effective "off-the-shelf" approach for rapid treatment of SARS-CoV-2 infection in case of sudden patient deterioration.
- Klíčová slova
- COVID-19, cellular therapies, immunotherapy, severe acute respiratory syndrome coronavirus 2, virus-specific T cells,
- MeSH
- COVID-19 * terapie MeSH
- cytokiny MeSH
- lidé MeSH
- SARS-CoV-2 * MeSH
- syndrom uvolnění cytokinů terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- cytokiny MeSH
Advanced therapy medicinal products (ATMPs) are medicines for human use based on genes, cells or tissue engineering. After clear successes in adults, the nascent technology now sees increasing pediatric application. For many still untreatable disorders with pre- or perinatal onset, timely intervention is simply indispensable; thus, prenatal and pediatric applications of ATMPs hold great promise for curative treatments. Moreover, for most inherited disorders, early ATMP application may substantially improve efficiency, economy and accessibility compared with application in adults. Vindicating this notion, initial data for cell-based ATMPs show better cell yields, success rates and corrections of disease parameters for younger patients, in addition to reduced overall cell and vector requirements, illustrating that early application may resolve key obstacles to the widespread application of ATMPs for inherited disorders. Here, we provide a selective review of the latest ATMP developments for prenatal, perinatal and pediatric use, with special emphasis on its comparison with ATMPs for adults. Taken together, we provide a perspective on the enormous potential and key framework parameters of clinical prenatal and pediatric ATMP application.
- Klíčová slova
- CAR NK cell, CAR T cell, gene therapy, hematopoietic stem and progenitor cell, mesenchymal stromal cell, somatic cell therapy, tissue-engineered medicinal product,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Acute lung injury is characterized by acute respiratory insufficiency with tachypnea, cyanosis refractory to oxygen, decreased lung compliance, and diffuse alveolar infiltrates on chest X-ray. The 1994 American-European Consensus Conference defined "acute respiratory distress syndrome, ARDS" by acute onset after a known trigger, severe hypoxemia defined by PaO2/FiO2=200 mm Hg, bilateral infiltrates on chest X-ray, and absence of cardiogenic edema. Milder form of the syndrome with PaO2/FiO2 between 200-300 mm Hg was named "acute lung injury, ALI". Berlin Classification in 2012 defined three categories of ARDS according to hypoxemia (mild, moderate, and severe), and the term "acute lung injury" was assigned for general description or for animal models. ALI/ARDS can originate from direct lung triggers such as pneumonia or aspiration, or from extrapulmonary reasons such as sepsis or trauma. Despite growing understanding the ARDS pathophysiology, efficacy of standard treatments, such as lung protective ventilation, prone positioning, and neuromuscular blockers, is often limited. However, there is an increasing evidence that direct and indirect forms of ARDS may differ not only in the manifestations of alterations, but also in the response to treatment. Thus, individualized treatment according to ARDS subtypes may enhance the efficacy of given treatment and improve the survival of patients.
- MeSH
- akutní poškození plic patofyziologie terapie MeSH
- lidé MeSH
- syndrom dechové tísně patofyziologie terapie MeSH
- umělé dýchání metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Background: Treatment with mesenchymal stem cells (MSCs) has elicited considerable interest as an adjunctive therapy in sepsis. However, the encouraging effects of experiments with MSC in rodents have not been adequately studied in large-animal models with better relevance to human sepsis. Objectives: Here, we aimed to assess safety and efficacy of bone marrow-derived MSCs in a clinically relevant porcine model of progressive peritonitis-induced sepsis. Methods: Thirty-two anesthetized, mechanically ventilated, and instrumented pigs were randomly assigned into four groups (n = 8 per group): (1) sham-operated group (CONTROL); (2) sham-operated group treated with MSCs (MSC-CONTROL); (3) sepsis group with standard supportive care (SEPSIS); and (4) sepsis group treated with MSCs (MSC-SEPSIS). Peritoneal sepsis was induced by inoculating cultivated autologous feces. MSCs (1 × 106/kg) were administered intravenously at 6 h after sepsis induction. Results: Before, 12, 18, and 24 h after the induction of peritonitis, we measured systemic, regional, and microvascular hemodynamics, multiple-organ functions, mitochondrial energy metabolism, systemic immune-inflammatory response, and oxidative stress. Administration of MSCs in the MSC-CONTROL group did not elicit any measurable acute effects. Treatment of septic animals with MSCs failed to mitigate sepsis-induced hemodynamic alterations or the gradual rise in Sepsis-related organ failure assessment scores. MSCs did not confer any protection against sepsis-mediated cellular myocardial depression and mitochondrial dysfunction. MSCs also failed to modulate the deregulated immune-inflammatory response. Conclusion: Intravenous administration of bone marrow-derived MSCs to healthy animals was well-tolerated. However, in this large-animal, clinically relevant peritonitis-induced sepsis model, MSCs were not capable of reversing any of the sepsis-induced disturbances in multiple biological, organ, and cellular systems.
- Klíčová slova
- acute organ dysfunction, cell therapy, immunomodulation, mesenchymal stem cells, sepsis, septic shock,
- MeSH
- modely nemocí na zvířatech MeSH
- náhodné rozdělení MeSH
- prasata MeSH
- sepse terapie MeSH
- transplantace mezenchymálních kmenových buněk metody MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH