Advances and potential of regenerative medicine in pediatric nephrology

Abstract

The endogenous capacity of the kidney to repair is limited, and generation of new nephrons after injury for adequate function recovery remains a need. Discovery of factors that promote the endogenous regenerative capacity of the injured kidney or generation of transplantable kidney tissue represent promising therapeutic strategies. While several encouraging results are obtained after administration of stem or progenitor cells, stem cell secretome, or extracellular vesicles in experimental kidney injury models, very little data exist in the clinical setting to make conclusions about their efficacy. In this review, we provide an overview of the cutting-edge knowledge on kidney regeneration, including pre-clinical methodologies used to elucidate regenerative pathways and describe the perspectives of regenerative medicine for kidney patients.

Developmental Causes of Focal Segmental Glomerulosclerosis

“…However, additional triggers or hits caused by environmental factors during childhood or early adulthood may induce reactivation of developmental pathways, which ultimately lead to the development of FSGS. A similar mechanism has been identified in kidney tubular cells from rodents as well as humans that indeed re-express developmental genes and proteins that include PAX2, LHX1, SOX9, GATA3 after injury [ 44 – 48 ]. Reactivation of these developmental pathways leads to expression of epidermal growth factor, insulin-like growth factor, transforming growth factor-β, and the canonical Wnt signaling pathway, which all are pivotal in cell fate determination and cell migration [ 49 ].…”

“…Additional integration with data from other multi-omics technologies and functional validation studies using model systems such as kidney organoids would ultimately provide a powerful approach to identify molecular targets for the development of tailored therapies for patients such as RNA interference and stem cell therapies to support or restore normal glomerular architecture. The effects of these targeted therapies are now studied in different functional models of kidney disease and transplantation with one of the main challenges being its delivery into the kidney [ 44 , 51 ].…”