Potential Therapeutic Effects of Long-Term Stem Cell Administration: Impact on the Gene Profile and Kidney Function of PKD/Mhm (Cy/+) Rats
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Daniela Nardozi1,2, Stefania Palumbo1, Arif Ul Maula Khan1
1Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer, 68167 Mannheim, Germany.
Abstract:
Cystic kidney disease (CKD) is a heterogeneous group of genetic disorders and one of the most common causes of end-stage renal disease. Here, we investigate the potential effects of long-term human stem cell treatment on kidney function and the gene expression profile of PKD/Mhm (Cy/+) rats. Human adipose-derived stromal cells (ASC) and human skin-derived ABCB5+ stromal cells (2 × 106) were infused intravenously or intraperitoneally monthly, over 6 months. Additionally, ASC and ABCB5+-derived conditioned media were administrated intraperitoneally. The gene expression profile results showed a significant reprogramming of metabolism-related pathways along with downregulation of the cAMP, NF-kB and apoptosis pathways. During the experimental period, we measured the principal renal parameters as well as renal function using an innovative non-invasive transcutaneous device. All together, these analyses show a moderate amelioration of renal function in the ABCB5+ and ASC-treated groups. Additionally, ABCB5+ and ASC-derived conditioned media treatments lead to milder but still promising improvements. Even though further analyses have to be performed, the preliminary results obtained in this study can lay the foundations for a novel therapeutic approach with the application of cell-based therapy in CKD.
Insights
Human stem cell therapy shows promise for treating cystic kidney disease (CKD). Treatments with adipose-derived stromal cells (ASC) and ABCB5+ stromal cells moderately improved kidney function in rats, offering a potential new therapeutic avenue.
Area of Science:
- Regenerative Medicine
- Nephrology
- Genetics
Background:
- Cystic kidney disease (CKD) is a genetic disorder leading to end-stage renal disease.
- Investigating novel therapeutic strategies for CKD is crucial.
Purpose of the Study:
- To evaluate the long-term effects of human stem cell treatments on kidney function and gene expression in a rat model of PKD.
- To explore the therapeutic potential of adipose-derived stromal cells (ASC) and ABCB5+ stromal cells in CKD.
Main Methods:
- Monthly intravenous or intraperitoneal infusion of ASC and ABCB5+ stromal cells (2 × 10^6) over 6 months.
- Administration of ASC and ABCB5+-derived conditioned media.
- Assessment of renal parameters and function using non-invasive transcutaneous device.
- Analysis of gene expression profiles to identify pathway changes.
Main Results:
- Significant reprogramming of metabolism-related pathways observed.
- Downregulation of cAMP, NF-kB, and apoptosis pathways.
- Moderate amelioration of renal function in ASC and ABCB5+ treated groups.
- Conditioned media treatments showed milder, yet promising, improvements in renal function.
Conclusions:
- Human stem cell therapy, including ASC and ABCB5+ cells, demonstrates potential for improving renal function in CKD.
- Cell-based therapies and conditioned media offer a novel therapeutic approach for managing cystic kidney disease.
- Further research is warranted to fully elucidate the therapeutic mechanisms and optimize treatment protocols.
