Organoids as a novel tool in modelling infectious diseases.

Infectious diseases worldwide affect human health and have important societal impacts. A better understanding of infectious diseases is urgently needed. In vitro and in vivo infection models have brought notable contributions to the current knowledge of these diseases. Organoids are multicellular culture systems resembling tissue architecture and function, recapitulating many characteristics of human disease and elucidating mechanisms of host-infectious agent interactions in the respiratory and gastrointestinal systems, the central nervous system and the skin. Here, we discuss the applicability of the organoid technology for modeling pathogenesis, host response and features, which can be explored for the development of preventive and therapeutic treatments.

Biomarkers in Hypertension and Hypertension-related Disorders.

Systemic arterial hypertension (SAH) is a major risk factor for several secondary diseases, especially cardiovascular and renal conditions. SAH has a high prevalence worldwide, and its precise and early recognition is important to prevent the development of secondary outcomes. In this field, the study of biomarkers represents an important approach to diagnosing and predicting the disease and its associated conditions. The use of biomarkers in hypertension and hypertension-related disorders, such as ischemic stroke, intracerebral hemorrhage, transient ischemic attack, acute myocardial infarction, angina pectoris and chronic kidney disease, are discussed in this review. Establishing a potential pool of biomarkers may contribute to a non-invasive and improved approach for their diagnosis, prognosis, risk assessment, therapy management and pharmacological responses to a therapeutic intervention to improve patients' quality of life and prevent unfavorable outcomes.

Enhancing the Therapeutic Potential of Mesenchymal Stem Cells with the CRISPR-Cas System.

Mesenchymal stem cells (MSCs), also known as multipotent mesenchymal stromal stem cells, are found in the perivascular space of several tissues. These cells have been subject of intense research in the last decade due to their low teratogenicity, as well as their ability to differentiate into mature cells and to secrete immunomodulatory and trophic factors. However, they usually promote only a modest benefit when transplanted in experimental disease models, one of the limitations for their clinical application. The CRISPR-Cas system, in turn, is highlighted as a simple and effective tool for genetic engineering. This system was tested in clinical trials over a relatively short period of time after establishing its applicability to the edition of the mammalian cell genome. Similar to the research evolution in MSCs, the CRISPR-Cas system demonstrated inconsistencies that limited its clinical application. In this review, we outline the evolution of MSC research and its applicability, and the progress of the CRISPR-Cas system from its discovery to the most recent clinical trials. We also propose perspectives on how the CRISPR-Cas system may improve the therapeutic potential of MSCs, making it more beneficial and long lasting.

Biological properties of cardiac mesenchymal stem cells in rats with diabetic cardiomyopathy.

Cardiomyopathy is a major outcome in patients with diabetes mellitus (DM) and contributes to the high morbidity/mortality observed in this disease. AIMS: To evaluate several biological properties of cardiac mesenchymal stem cells (cMSCs) in a rat model of streptozotocin-induced DM with concomitant diabetic cardiomyopathy. MAIN METHODS: After 10weeks of DM induction, diabetic and control rats were assessed using ECG and ventricular hemodynamics monitoring. Then, the hearts were excised and processed for histology and for extracting non-cardiomyocytic cells. A pool of these cells was plated for a colony forming units-fibroblasts (CFU-F) assay in order to estimate the number of cMSCs. The remaining cells were expanded to assess their proliferation rate as well as their osteogenic and adipogenic differentiation ability. KEY FINDINGS: DM rats presented intense hyperglycemia and changes in ECG, LV hemodynamic, cardiac mass index and fibrosis, indicating presence of DCM. The CFU-F assay revealed a higher number of cardiac CFU-Fs in DM rats (10.4±1.1CFU-F/105 total cells versus 7.6±0.7CFU-F/105 total cells in control rats, p<0.05), which was associated with a significantly higher proliferative rate of cMSCs in DM rats. In contrast, cMSCs from DM rats presented a lower capacity to differentiate into both osteogenic (20.8±4.2% versus 10.1±1.0% in control rats, p<0.05) and adipogenic lineages (4.6±1.0% versus 1.3±0.5% in control rats, p<0.05). SIGNIFICANCE: The findings suggest, for the first time, that in chronic DM rats with overt DCM, cMSCs increase in number and exhibit changes in several functional properties, which could be implicated in the pathogenesis of diabetic cardiomyopathy.