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Published on: August 7, 2017
Mesenchymal Stromal Cells Improve Renovascular Function in Polycystic Kidney Disease
Federico Franchi1, Karen M Peterson, Rende Xu
1Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
Insights
Mesenchymal stromal cells (MSCs) improved kidney structure and function in a polycystic kidney disease (PKD) rat model. This cell-based therapy offers a novel approach for treating PKD, a common cause of kidney failure.
Area of Science:
- Nephrology
- Regenerative Medicine
- Stem Cell Biology
Background:
- Polycystic kidney disease (PKD) is a leading cause of end-stage renal failure with no current effective treatments.
- Renovascular disease models show that progenitor and stem cells can restore renal function, suggesting potential for PKD.
- Adult stem cells offer a promising avenue for therapeutic intervention in degenerative renal diseases like PKD.
Purpose of the Study:
- To investigate the efficacy of adult stem cells in restoring renal structure and function in a polycystic kidney disease (PKD) model.
- To evaluate the impact of mesenchymal stromal cells (MSCs) on blood pressure, kidney function, and renal pathology in PCK rats.
- To assess the long-term effects of MSC infusion on vascularity, fibrosis, and cyst development in PKD.
Main Methods:
- Bone marrow-derived mesenchymal stromal cells (MSCs) were administered via intrarenal infusion to 6-week-old PCK rats.
- Systolic blood pressure (SBP) and creatinine clearance were measured to assess renal function.
- Microcomputed tomography was used to evaluate vascular density and glomeruli diameter.
- Urine osmolality, renal fibrosis, and proangiogenic molecule expression were analyzed post-treatment.
Main Results:
- MSC treatment significantly improved systolic blood pressure and creatinine clearance in PCK rats compared to untreated PKD animals.
- Vascular density and glomeruli diameter were preserved in MSC-treated PCK rats.
- Urine osmolality was improved following MSC infusion, returning to levels comparable to control rats.
- MSCs reduced renal fibrosis and maintained proangiogenic molecule expression, though cyst size and number remained unchanged.
Conclusions:
- Exogenous MSC delivery enhances renal vascularity and function in a preclinical model of polycystic kidney disease.
- Cell-based therapy with MSCs demonstrates potential as a novel therapeutic strategy for polycystic kidney disease.
- The observed benefits of MSCs on renal function and structure persisted for at least four weeks after a single infusion, highlighting the potential for sustained therapeutic effects.
Abstract:
Polycystic kidney disease (PKD) is a common cause of end-stage renal failure, for which there is no accepted treatment. Progenitor and stem cells have been shown to restore renal function in a model of renovascular disease, a disease that shares many features with PKD. The objective of this study was to examine the potential of adult stem cells to restore renal structure and function in PKD. Bone marrow-derived mesenchymal stromal cells (MSCs, 2.5 × 10(5)) were intrarenally infused in 6-week-old PCK rats. At 10 weeks of age, PCK rats had an increase in systolic blood pressure (SBP) versus controls (126.22 ± 2.74 vs. 116.45 ± 3.53 mmHg, p < 0.05) and decreased creatinine clearance (3.76 ± 0.31 vs. 6.10 ± 0.48 µl/min/g, p < 0.01), which were improved in PKD animals that received MSCs (SBP: 114.67 ± 1.34 mmHg, and creatinine clearance: 4.82 ± 0.24 µl/min/g, p = 0.001 and p = 0.003 vs. PKD, respectively). MSCs preserved vascular density and glomeruli diameter, measured using microcomputed tomography. PCK animals had increased urine osmolality (843.9 ± 54.95 vs. 605.6 ± 45.34 mOsm, p < 0.01 vs. control), which was improved after MSC infusion and not different from control (723.75 ± 56.6 mOsm, p = 0.13 vs. control). Furthermore, MSCs reduced fibrosis and preserved the expression of proangiogenic molecules, while cyst size and number were unaltered by MSCs. Delivery of exogenous MSCs improved vascular density and renal function in PCK animals, and the benefit was observed up to 4 weeks after a single infusion. Cell-based therapy constitutes a novel approach in PKD.
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