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This study aimed to investigate whether these SIX2-positive urine-derived renal progenitor cells (UdRPC) have therapeutic potential in treating or managing acute to chronic kidney injuries, which are increasing worldwide and currently affect one in ten people. Human UdRPC were obtained from a 35-year-old woman, expanded, and characterized in vitro before being transplanted unilaterally under the renal capsule of mouse kidneys that had undergone ischemia reperfusion injury (IRI). The blood sera of the mice were examined for kidney injury markers such as blood-urea-nitrogen and creatinine, and proteome changes over the 21-day study period using proteome arrays and bioinformatic methods. At the end of the study period, connective tissue deposition in the kidneys was examined histologically through Sirius Red staining, and the expression of fibrosis- and inflammation-associated genes was determined by reverse transcription quantitative polymerase chain reaction. The blood serum analysis revealed that the transplanted human UdRPC transiently influenced the secretome in mice. Furthermore, the transplanted cells improved renal fibrosis resulting from IRI, indicating therapeutic relevance. Deposition of extracellular matrix proteins and the expression of fibrosis-associated genes, such as connective tissue growth factor as well as collagen 1\u03b12 and 3\u03b11 chains, significantly decreased in the injured kidney after UdRPC transplantation. The expression of genes linked to inflammation and chronic kidney disease, such as monocyte chemoattractant protein 1 and intercellular adhesion molecule 1, was also reduced in mouse kidneys in the presence of UdRPC. K-means cluster analysis of the serum proteome from mice with IRI and transplanted UdRPC at different time points revealed a transient increase in immunomodulatory, antifibrotic, and angiogenic factors that could have triggered these positive effects on acute to chronic mouse kidney disease. Transplanted human UdRPC alleviated the kidney injury severity through ameliorating fibrosis; however, they could not restore complete kidney function within 21 days.<\/jats:p>","DOI":"10.1177\/15473287251388416","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T05:56:16Z","timestamp":1761890176000},"page":"472-482","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Human Urine-Derived SIX2-Positive Renal Progenitor Cells Partially Improve Kidney Fibrosis by Paracrine Signaling"],"prefix":"10.1177","volume":"34","author":[{"given":"Claus","family":"Kordes","sequence":"first","affiliation":[{"name":"Institute of Stem Cell Research and Regenerative Medicine, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich-Heine University D\u00fcsseldorf, D\u00fcsseldorf, 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