Clinical Trials with Mesenchymal Stem Cell Therapies for Osteoarthritis: Challenges in the Regeneration of Articular Cartilage.

Osteoarthritis (OA) is a whole-joint disease primarily characterized by the deterioration of hyaline cartilage. Current treatments include microfracture and chondrocyte implantation as early surgical strategies that can be combined with scaffolds to repair osteochondral lesions; however, intra-articular (IA) injections or implantations of mesenchymal stem cells (MSCs) are new approaches that have presented encouraging therapeutic results in animal models and humans. We critically reviewed clinical trials with MSC therapies for OA, focusing on their effectiveness, quality, and outcomes in the regeneration of articular cartilage. Several sources of autologous or allogeneic MSCs were used in the clinical trials. Minor adverse events were generally reported, indicating that IA applications of MSCs are potentially safe. The evaluation of articular cartilage regeneration in human clinical trials is challenging, particularly in the inflammatory environment of osteoarthritic joints. Our findings indicate that IA injections of MSCs are efficacious in the treatment of OA and the regeneration of cartilage, but that they may be insufficient for the full repair of articular cartilage defects. The possible interference of clinical and quality variables in the outcomes suggests that robust clinical trials are still necessary for generating reliable evidence with which to support these treatments. We suggest that the administration of just-sufficient doses of viable cells in appropriate regimens is critical to achieve effective and durable effects. In terms of future perspectives, genetic modification, complex products with extracellular vesicles derived from MSCs, cell encapsulation in hydrogels, and 3D bioprinted tissue engineering are promising approaches with which to improve MSC therapies for OA.

Aumento dos fatores de risco e suscetibilidade para o desenvolvimento de eventos tromboembólicos em indivíduos portadores de doença falciforme infectados pela Covid-19: uma revisão integrativa / Increased risk and susceptibility factors for the development of thromboembolic events in individuals with sickle cell disease infected by Covid-19: an integrative review

Introdução: diante das preocupações causadas pela pandemia do novo Corona vírus e doença relacionada (COVID-19), seja para profissionais de saúde ou da sociedade em geral, estudos relacionados aos riscos para indivíduos com doença falciforme (DF) são ainda escassos. A doença falciforme possui um estado de hipercoagulabilidade, inclusive em pacientes estáveis, sendo assim, a infecção causada pela COVID-19 possivelmente agrava as manifestações fisiopatológicas desses pacientes, podendo ter consequências fatais. Objetivo: identificar eventos tromboembólicos causados pela COVID-19 que são frequentes na DF e podem trazer complicações para esses indivíduos, com consequente aumento do risco de mortalidade. Metodologia: revisão integrativa, onde foram identificados inicialmente 278 estudos, dos quais 264 foram excluídos, sendo então mantidos 14 artigos, os quais foram categorizados conforme o desenho estabelecido para cada um destes estudos, considerando como critérios de qualidade os itens definidos na escala PEDro, associados a outros parâmetros sugestivos de artigos de boa qualidade, como o Índice H, fator de impacto, representatividade dos autores na área do estudo e instituições as quais estes autores estão vinculados. Resultados: com base nas informações descritas, identificou-se o risco aumentado de indivíduos portadores de doença falciforme para o desenvolvimento de eventos tromboembólicos graves diante da exposição à COVID-19. Conclusão: o indivíduo portador de Doença Falciforme diante da infecção pela COVID-19 tem maior risco e suscetibilidade de desenvolvimento de complicações tromboembólicas, consequentemente aumentando suas chances de mortalidade. É de grande importância a realização de estudos clínicos sobre os efeitos tromboembólicos da COVID-19 em pacientes com DF devendo ser incentivados.

Introduction: in view of the concerns caused by the new Coronavirus pandemic and its disease (COVID-19), whether for health professionals or society in general, studies related to the risks for diseases with Sickle Cell Disease (SCD) are still scarce. Sickle cell disease has a state of hypercoagulability, even in stable patients, thus, an infection caused by COVID-19, possibly worsens the pathophysiological manifestations of these patients, which can have fatal consequences. Objective: to identify thromboembolic events caused by COVID-19, which are frequent in the SCD and can cause complications for these individuals, with a consequent increase in the risk of mortality. Methodology: integrative review, in which 278 studies were identified, of which 264 were excluded, and 14 articles were then kept, and they were categorized according to the design established for each of these studies, considering as quality criteria the items written in PEDro scale, associated with other criteria suggestive of good quality articles, such as H Index, impact factor, representativeness of authors in the study area and institutions, such as which these authors are linked to. Results: based on the information described, an increased risk of patients with sickle cell disease for the development of serious thromboembolic events exposed to exposure to COVID-19 was identified. Conclusion: people diagnosed with Sickle Cell Disease if infected with COVID-19 have a higher risk and susceptibility to the development of thromboembolic complications, consequently enhancing their chances of mortality. Clinical studies on thromboembolic effects of COVID-19 in patients with DF are of great importance and must be encouraged.