The explosion of the new coronavirus (SARS-CoV-2) pandemic has brought the role of the angiotensin converting enzyme 2 (ACE2) back into the scientific limelight. Since SARS-CoV-2 must bind the ACE2 for entering the host cells in humans, its expression and body localization are critical to track the potential target organ of this infection and to outline disease progression and clinical outcomes. Here, we mapped the physiological body distribution, expression, and activities of ACE2 and discussed its potential correlations and mutal interactions with the disparate symptoms present in SARS-CoV-2 patients at the level of different organs. We highlighted that despite during SARS-CoV-2 infection ACE2-expressing organs may become direct targets, leading to severe pathological manifestations, and subsequent multiple organ failures, the exact mechanism and the potential interactions through which ACE2 acts in these organs is still heavily debated. Further scientific efforts, also considering a personalized approach aimed to consider specific patient differences in the mutual interactions ACE2-SARS-CoV-2 and the long-term health effects associated with COVID-19 are currently mandatory.
Coronavirus disease 2019 (COVID-19) is a new infectious disease that currently lacks standardized and established laboratory markers to evaluate its severity. In COVID-19 patients, the number of platelets (PLTs) and dynamic changes of PLT-related parameters are currently a concern. The present paper discusses the potential link between PLT parameters and COVID-19. Several studies have identified a link between severe COVID-19 patients and specific coagulation index, in particular, high D-dimer level, prolonged prothrombin time, and low PLT count. These alterations reflect the hypercoagulable state present in severe COVID-19 patients, which could promote microthrombosis in the lungs, as well as in other organs. Further information and more advanced hematological parameters related to PLTs are needed to better estimate this link, also considering COVID-19 patients at different disease stages and stratified in different cohorts based on preexisting co-morbidity, age, and gender. Increasing the understanding of PLT functions in COVID-19 will undoubtedly improve our knowledge on disease pathogenesis, clinical management, and therapeutic options, but could also lead to the development of more precise therapeutic strategies for COVID-19 patients.
Several therapeutic approaches have been developed to address hyaline cartilage regeneration, but to date, there is no universal procedure to promote the restoration of mechanical and functional properties of native cartilage, which is one of the most important challenges in orthopedic surgery. For cartilage tissue engineering, adult mesenchymal stem cells (MSCs) are considered as an alternative cell source to chondrocytes. Since little is known about adipose-derived mesenchymal stem cell (ADSC) cartilage regeneration potential, the aim of this review was to give an overview of in vivo studies about the chondrogenic potential and regeneration ability of culture-expanded ADSCs when implanted in heterotopic sites or in osteoarthritic and osteochondral defects. The review compares the different studies in terms of number of implanted cells and animals, cell harvesting sites, in vitro expansion and chondrogenic induction conditions, length of experimental time, defect dimensions, used scaffolds and post-explant analyses of the cartilage regeneration. Despite variability of the in vivo protocols, it seems that good cartilage formation and regeneration were obtained with chondrogenically predifferentiated ADSCs (1 × 10(7) cells for heterotopic cartilage formation and 1 × 10(6) cells/scaffold for cartilage defect regeneration) and polymeric scaffolds, even if many other aspects need to be clarified in future studies.
Despite its pervasive use, the clinical efficacy of platelet-rich plasma (PRP) therapy and the different mechanisms of action have yet to be established. This overview of the literature is focused on the role of PRP in bone, tendon, cartilage, and ligament tissue regeneration considering basic science literature deriving from in vitro and in vivo studies. Although this work provides evidence that numerous preclinical studies published within the last 10 years showed promising results concerning the application of PRP, many key questions remain unanswered and controversial results have arisen. Additional preclinical studies are needed to define the dosing, timing, and frequency of PRP injections, different techniques for delivery and location of delivery, optimal physiologic conditions for injections, and the concomitant use of recombinant proteins, cytokines, additional growth factors, biological scaffolds, and stems cells to develop optimal treatment protocols that can effectively treat various musculoskeletal conditions.
While the skeleton is not the only organ where metastasis can occur, it is one of the preferred sites, with a significant impact in patients' quality of life. With the aim of delineating the cellular and molecular mechanisms of bone metastasis, numerous studies have been employed to identify any contributing factors that trigger cancer progression. One of the major limitations of studying cancer-bone metastasis is the multifaceted nature of the native bone environment and the lack of reliable, simple, and not expensive models that strictly mimic the biological processes occurring in vivo allowing a correct translation of results. Currently, with the growing acceptance of in vitro models as effective tools for studying cancer biology, three-dimensional (3D) models have emerged as a compromise between two-dimensional cultures of isolated cancer cells and the complexity of human cancer xenografts in immunocompromised animal hosts. This descriptive systematic literature review summarizes the current status of advanced and alternative 3D in vitro bone metastases models. We have also reviewed the strategies employed by researchers to set-up these models with special reference to recent promising developments trying to better replicate the complexity and heterogeneity of a human metastasis in situ, with an outlook at their use in medicine. All these aspects will greatly contribute to the existing knowledge on bone metastases, providing a specific link to clinical scenarios and thus making 3D in vitro bone metastasis models an attractive tool for multidisciplinary experts.
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