Abstract
A BSTRACT Background: Kidney transplantation remains the preferred treatment for kidney failure, yet ischemia–reperfusion injury, alloimmune activation, chronic inflammation, fibrosis, and the toxicities of long-term immunosuppression continue to compromise graft longevity. The objective is to synthesize the author-provided literature on stem cell–based strategies relevant to kidney transplantation and identify the most promising translational directions. Methods: This narrative review was completed from nine full-text articles supplied for this project, including direct kidney transplantation studies, mechanistic experimental work, and supportive reviews on immune tolerance, immunosenescence, and regenerative cell platforms. Results: Across the provided literature, hematopoietic stem cell transplantation-based chimerism offers the strongest clinical proof that cell therapy can permit immunosuppression minimization or withdrawal in carefully selected living-donor kidney transplants. Mesenchymal stromal cells are the most extensively studied immunomodulatory platform and act primarily through paracrine mediators, extracellular vesicles (EVs), efferocytosis-driven macrophage reprogramming, and regulatory T-cell support. In kidney transplant cohorts, mesenchymal stromal cells have shown safety and biologic activity, but efficacy remains heterogeneous and may be accompanied by donor-specific antibody signals in some settings. Cell-free EVs/exosomes are particularly attractive for peri-transplant cytoprotection; experimental data support anti-inflammatory, anti-pyroptotic, and cytoprotective effects through ATF3 upregulation and inhibition of the TLR4/nuclear factor kappa B pathway. Renal progenitor, selected renal cell, and induced pluripotent stem cell-derived platforms extend the field toward personalized regeneration, but transplant-specific validation remains limited. Conclusions: The field is shifting from proof-of-concept toward mechanism-guided translation, but durable benefit will require better potency assays, standardized manufacturing, optimized route and timing of delivery, and biomarker-guided patient selection.