Human Urine-Derived SIX2-Positive Renal Progenitor Cells Partially Improve Kidney Fibrosis by Paracrine Signaling

Area of Science:

• Regenerative Medicine
• Nephrology
• Stem Cell Biology

Background:

• Acute to chronic kidney injuries affect 1 in 10 people globally.
• SIX2-positive cells with renal progenitor characteristics are found in urine.
• There is a need for novel therapeutic strategies for kidney injury.

Purpose of the Study:

• To investigate the therapeutic potential of human urine-derived renal progenitor cells (UdRPC) for acute to chronic kidney injuries.
• To assess the effects of UdRPC transplantation on kidney injury markers, fibrosis, and inflammation in a mouse model.

Main Methods:

• Human UdRPC were isolated, expanded, and characterized in vitro.
• UdRPC were transplanted into mouse kidneys with ischemia reperfusion injury (IRI).
• Kidney injury markers, proteome changes, fibrosis, and gene expression were analyzed.

Main Results:

• Transplanted UdRPC transiently modulated the mouse secretome.
• UdRPC transplantation significantly reduced renal fibrosis and extracellular matrix deposition.
• Expression of fibrosis-, inflammation-, and chronic kidney disease-associated genes decreased post-transplantation.

Conclusions:

• Human UdRPC demonstrated therapeutic relevance in ameliorating kidney injury severity, primarily through antifibrotic effects.
• Transplanted UdRPC induced a transient increase in beneficial immunomodulatory, antifibrotic, and angiogenic factors.
• While UdRPC alleviated fibrosis, complete kidney function restoration was not observed within the 21-day study period.