Induced pluripotent stem cells provide mega insights into kidney disease

Abstract

Rare mutations in the LRP2 gene encoding for the endocytic receptor megalin cause developmental abnormalities and kidney disease. However, the mechanisms governing the dysfunction of mutant megalin remain unclear. A new study utilizing patient-derived induced pluripotent stem cells is now putting the endolysosomal system into the spotlight, as it is proposed to play a central role in the regulation of megalin in health and disease.

Mitochondrial disease, mitophagy, and cellular distress in methylmalonic acidemia

“…Assessments of the mode of action of protein-damaging mutations require proof-of-concept studies in physiologically relevant cell culture based-systems. Traditional cell-based models typically rely on cancer-derived or immortalized cells that fail to adequately recapitulate the complex features of the in vivo disease phenotype [ 133 ]. The use of patient-derived primary cell samples aims thus to overwhelm the disadvantages and limitations of using transformed cell lines for dissecting disease mechanisms.…”

Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy

“…The iPSCs possess several key characteristics that are highly relevant to the characterization of neural stem/progenitor cells (NS/PCs) derived from human iPSCs. Firstly, iPSCs share the defining feature of pluripotency, meaning they have the potential to differentiate into cells of all three germ layers, including neural cells [ 70 ]. This property allows for the generation of NS/PCs from iPSCs, serving as a valuable model system for studying neural development and disease.…”

“…Additionally, iPSCs exhibit self-renewal capacity, allowing them to proliferate indefinitely in culture, thereby providing a sustainable source of NS/PCs for experimentation and potential therapeutic applications. Lastly, iPSCs can be genetically modified to introduce specific mutations or gene editing techniques, facilitating the investigation of genetic factors underlying neural development and diseases [ 70 ]. Isoda et al, the research focuses on understanding the tumorigenic potential of neural stem/progenitor cells derived from human induced pluripotent stem cells (hiPSC-NS/PCs), which are considered a promising source for cell-based therapies.…”

“…These reprogramming factors can reset the cellular state, erasing the specialized characteristics of the somatic cells and reverting them back to a pluripotent state [74]. The most commonly used reprogramming factors are Oct4 (octamer-binding transcription factor 4), Sox2 (sex-determining region Y-box 2), Klf4 Limited differentiation potential [70] (Kruppel-like factor 4), and c-Myc (avian myelocytomatosis viral oncogene homolog) [20]. These factors work together to induce the expression of genes associated with pluripotency, while simultaneously repressing genes involved in cellular differentiation.…”