The Potential and Challenges of Human Pluripotent Stem Cells in the Treatment of Diabetic Nephropathy.

Diabetic nephropathy (DN) is a prevalent complication of diabetes, with current treatment options offering limited effectiveness, particularly in advanced stages. Human pluripotent stem cells (hPSCs), particularly induced PSCs (iPSCs), show promising potential in the treatment of DN due to their pluripotency, capacity for differentiation into kidney-specific cells, and suitability for personalized therapies. iPSC-based personalized approaches can effectively mitigate immune rejection, a common challenge with allogeneic transplants, thus enhancing therapeutic outcomes. Clustered regularly interspaced short palindromic repeats (CRISPR) gene editing further enhances the potential of hPSCs by enabling the precise correction of disease-associated genetic defects, increasing both the safety and efficacy of therapeutic cells. In addition to direct treatment, hPSCs have proven valuable in disease modeling and drug screening, particularly for identifying and validating disease-specific targets. Kidney organoids derived from hPSCs replicate key features of DN pathology, making them useful platforms for validating therapeutic targets and assessing drug efficacy. Comparatively, both hPSCs and mesenchymal SCs (MSCs) have shown promise in improving renal function in preclinical models, with hPSCs offering broader differentiation capacity. Integration with tissue engineering technologies, such as three-dimensional bioprinting and bioengineered scaffolds, expands the regenerative potential of hPSCs by supporting the formation of functional renal structures and enhancing integration and regenerative capacity. Despite current challenges, such as tumorigenicity, genomic instability, and limited direct research, advances in gene editing, differentiation protocols, and tissue engineering promise to address these barriers. Continued optimization of these approaches will likely lead to successful clinical applications of hPSCs, potentially revolutionizing treatment options for DN.