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Unveiling spontaneous renal tubule-like structures from human adult renal progenitor cell spheroids derived from urine
    #29650009 -

Unveiling spontaneous renal tubule-like structures from human adult renal progenitor cell spheroids derived from urine

https://pubmed.ncbi.nlm.nih.gov/40156847/


Abstract
The rapidly developing field of renal spheroids and organoids has emerged as a valuable tool for modeling nephrotoxicity, kidney disorders, and kidney development. However, existing studies have relied on intricate and sophisticated differentiation protocols to generate organoids and tubuloids, necessitating the external administration of multiple growth factors within precise timeframes. In our study, we demonstrated that human adult renal progenitor cells (ARPCs) isolated from the urine of both healthy subjects and patients can form spheroids that naturally generated very long tubule-like structures. Importantly, the generation of these tubule-like structures is driven solely by ARPCs, without the need for the external use of chemokines or growth factors to artificially induce this process. These tubule-like structures exhibit the expression of structural and functional renal tubule markers and bear, in some cases, striking structural similarities to various nephron regions, including the distal convoluted tubule, the loop of Henle, and proximal convoluted tubules. Furthermore, ARPC spheroids express markers typical of pluripotent cells, such as stage-specific embryonic antigen 4 (SSEA4), secrete elevated levels of renin, and exhibit angiogenic properties. Notably, ARPCs isolated from the urine of patients with IgA nephropathy form spheroids capable of recapitulating the characteristic IgA1 deposition observed in this disease. These findings represent significant advancements in the field, opening up new avenues for regenerative medicine in the study of kidney development, mechanisms underlying renal disorders, and the development of regenerative therapies for kidney-related ailments.

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Re: Unveiling spontaneous renal tubule-like structures from human adult renal progenitor cell spheroids derived from urine [Re: Myco-A-E]
    #29650010 -

The Regenerative Potential of Human Adult Renal Stem/Progenitor Cells

https://link.springer.com/rwe/10.1007/978-981-99-7119-0_24

Abstract
The human adult renal stem/progenitor cells (ARPCs) play a role in renal regeneration in two ways: by differentiating directly or by secreting reparative molecules. They can differentiate into epithelial, endothelial, osteogenic, and adipogenic cells. ARPCs can regenerate long segments of renal tubules and also missing podocytes in cortical nephrons after acute kidney injury (AKI). These renal progenitors express the Toll-Like Receptor 2 (TLR2); they are activated by TLR2 ligands and can secrete restorative and therapeutic factors capable of repairing renal tubular cells damaged. The TLR2 can act as a damaged sensor, and its activation can cause stem cell proliferation and differentiation, among other things. Kidney progenitors can repair physical and chemical damage, such as a wound in epithelial tissue or damage caused by cisplatin, a widely used chemotherapy drug that can cause nephrotoxic side effects. Following renal tubular cell damage, ARPCs release inhibin-A and decorin, which are directly involved in cell regeneration. The ARPCs can also prevent endothelial dysfunction and protect the endothelial compartment following exposure to lipopolysaccharides (LPS), thus promoting kidney repair. They exert an anti-fibrotic effect through the secretion of antiseptic molecules CXCL6, SAA4, and BPIFA2. Moreover, ARPCs possess immunomodulatory capabilities towards CD3+ CD4-CD8- (double negative; DN) T-lymphocytes and can promote regulatory T lymphocytes (Treg). In addition, it has been discovered that renal progenitors, thanks to the high expression of HOTAIR, can secrete high quantities of α-Klotho, an anti-aging protein capable of influencing the surrounding tissues and therefore modulating renal aging. These data open new perspectives on treating diseases, suggesting an underestimated role of ARPCs in preventing and repairing kidney injuries and novel strategies to protect the endothelial compartment and promote kidney repair.

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