Urine-based therapy, an ancient practice, has been utilized across numerous civilizations to address a wide range of ailments. Urine was considered a priceless resource in numerous traditional therapeutic applications due to its reported medicinal capabilities. While the utilization of urine treatment is contentious and lacks significant support from modern healthcare, the discovery of urine-derived stem cells (UDSCs) has introduced a promising avenue for cell-based therapy. UDSCs offer a noninvasive and easily repeatable collection method, making them a practical and viable option for therapeutic applications. Research has shown that UDSCs contribute to organ preservation by promoting revascularization and decreasing inflammatory reactions in many diseases and conditions. This review will outline the contemporary status of UDSCs research and explore their potential applications in both fundamental science and medical practice.

Cortical organoids derived from human induced pluripotent stem cells (hiPSCs) represent a powerful in vitro experimental system to investigate human brain development and disease, often inaccessible to direct experimentation. However, despite steady progress in organoid technology, several limitations remain, including high cost and variability, use of hiPSCs derived from tissues harvested invasively, unexplored three-dimensional (3D) structural features and neuronal connectivity. Here, using a cost-effective and reproducible protocol as well as conventional two-dimensional (2D) immunostaining, we show that cortical organoids generated from hiPSCs obtained by reprogramming stem cells from human exfoliated deciduous teeth (SHED) recapitulate key aspects of human corticogenesis, such as polarized organization of neural progenitor zones with the presence of outer radial glial stem cells, and differentiation of superficial- and deep-layer cortical neurons and glial cells. We also show that 3D bioprinting and magnetic resonance imaging of intact cortical organoids are alternative and complementary approaches to unravel critical features of the 3D architecture of organoids. Finally, extracellular electrical recordings in whole organoids showed functional neuronal networks. Together, our findings suggest that SHED-derived cortical organoids constitute an attractive model of human neurodevelopment, and support the notion that a combination of 2D and 3D techniques to analyze organoid structure and function may help improve this promising technology.

The field of regenerative medicine has witnessed remarkable advancements with the emergence of induced pluripotent stem cells (iPSCs) derived from a variety of sources. Among these, urine-derived induced pluripotent stem cells (u-iPSCs) have garnered substantial attention due to their non-invasive and patient-friendly acquisition method. This review manuscript delves into the potential and application of u-iPSCs in advancing precision medicine, particularly in the realms of drug testing, disease modeling, and cell therapy. U-iPSCs are generated through the reprogramming of somatic cells found in urine samples, offering a unique and renewable source of patient-specific pluripotent cells. Their utility in drug testing has revolutionized the pharmaceutical industry by providing personalized platforms for drug screening, toxicity assessment, and efficacy evaluation. The availability of u-iPSCs with diverse genetic backgrounds facilitates the development of tailored therapeutic approaches, minimizing adverse effects and optimizing treatment outcomes. Furthermore, u-iPSCs have demonstrated remarkable efficacy in disease modeling, allowing researchers to recapitulate patient-specific pathologies in vitro. This not only enhances our understanding of disease mechanisms but also serves as a valuable tool for drug discovery and development. In addition, u-iPSC-based disease models offer a platform for studying rare and genetically complex diseases, often underserved by traditional research methods. The versatility of u-iPSCs extends to cell therapy applications, where they hold immense promise for regenerative medicine. Their potential to differentiate into various cell types, including neurons, cardiomyocytes, and hepatocytes, enables the development of patient-specific cell replacement therapies. This personalized approach can revolutionize the treatment of degenerative diseases, organ failure, and tissue damage by minimizing immune rejection and optimizing therapeutic outcomes. However, several challenges and considerations, such as standardization of reprogramming protocols, genomic stability, and scalability, must be addressed to fully exploit u-iPSCs' potential in precision medicine. In conclusion, this review underscores the transformative impact of u-iPSCs on advancing precision medicine and highlights the future prospects and challenges in harnessing this innovative technology for improved healthcare outcomes.

In vitro and in vivo models play integral roles in preclinical drug research, evaluation, and precision medicine. In vitro models primarily involve research platforms based on cultured cells, typically in the form of two-dimensional (2D) cell models. However, notable disparities exist between 2D cultured cells and in vivo cells across various aspects, rendering the former inadequate for replicating the physiologically relevant functions of human or animal organs and tissues. Consequently, these models failed to accurately reflect real-life scenarios post-drug administration. Complex in vitro models (CIVMs) refer to in vitro models that integrate a multicellular environment and a three-dimensional (3D) structure using bio-polymer or tissue-derived matrices. These models seek to reconstruct the organ- or tissue-specific characteristics of the extracellular microenvironment. The utilization of CIVMs allows for enhanced physiological correlation of cultured cells, thereby better mimicking in vivo conditions without ethical concerns associated with animal experimentation. Consequently, CIVMs have gained prominence in disease research and drug development. This review aimed to comprehensively examine and analyze the various types, manufacturing techniques, and applications of CIVM in the domains of drug discovery, drug development, and precision medicine. The objective of this study was to provide a comprehensive understanding of the progress made in CIVMs and their potential future use in these fields.

ChatGPT, an advanced language generation model developed by OpenAI, has the potential to revolutionize healthcare delivery and support for individuals with various conditions, including Down syndrome. This article explores the applications of ChatGPT in assisting children with Down syndrome, highlighting the benefits it can bring to their education, social interaction, and overall well-being. While acknowledging the challenges and limitations, we examine how ChatGPT can be utilized as a valuable tool in enhancing the lives of these children, promoting their cognitive development, and supporting their unique needs.

Stem cells have potential applications in the field of neurological diseases, as they allow for the development of new biological models. These models can improve our understanding of the underlying pathologies and facilitate the screening of new therapeutics in the context of precision medicine. Stem cells have also been applied in clinical tests to repair tissues and improve functional recovery. Nevertheless, although promising, commonly used stem cells display some limitations that curb the scope of their applications, such as the difficulty of obtention. In that regard, urine-derived cells can be reprogrammed into induced pluripotent stem cells (iPSCs). However, their obtaining can be challenging due to the low yield and complexity of the multi-phased and typically expensive differentiation protocols. As an alternative, urine-derived stem cells (UDSCs), included within the population of urine-derived cells, present a mesenchymal-like phenotype and have shown promising properties for similar purposes. Importantly, UDSCs have been differentiated into neuronal-like cells, auspicious for disease modeling, while overcoming some of the shortcomings presented by other stem cells for these purposes. Thus, this review assesses the current state and future perspectives regarding the potential of UDSCs in the ambit of neurological diseases, both for disease modeling and therapeutic applications.

Down syndrome (DS), caused by triplication of chromosome 21, is the most frequent aneuploidy observed in the human population and represents the most common genetic form of intellectual disability and early-onset Alzheimer's disease (AD). Individuals with DS exhibit a wide spectrum of clinical presentation, with a number of organs implicated including the neurological, immune, musculoskeletal, cardiac, and gastrointestinal systems. Decades of DS research have illuminated our understanding of the disorder, however many of the features that limit quality of life and independence of individuals with DS, including intellectual disability and early-onset dementia, remain poorly understood. This lack of knowledge of the cellular and molecular mechanisms leading to neurological features of DS has caused significant roadblocks in developing effective therapeutic strategies to improve quality of life for individuals with DS. Recent technological advances in human stem cell culture methods, genome editing approaches, and single-cell transcriptomics have provided paradigm-shifting insights into complex neurological diseases such as DS. Here, we review novel neurological disease modeling approaches, how they have been used to study DS, and what questions might be addressed in the future using these innovative tools.