Mesenchymal stromal cells improve renovascular function in polycystic kidney disease

Federico Franchi, Karen M. Peterson, Rende Xu, Brent Miller, Peter J. Psaltis, Peter C Harris, Lilach O Lerman, Martin G Rodriguez-Porcel

Research output: Contribution to journalArticle

13 Scopus citations

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<sup>5</sup>) 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.

Original languageEnglish (US)
Pages (from-to)1687-1698
Number of pages12
JournalCell Transplantation
Volume24
Issue number9
DOIs
StatePublished - Sep 14 2015

Keywords

  • Kidney
  • Mesenchymal stromal cells (MSCs)
  • Polycystic kidney disease (PKD)
  • Renal function
  • Vasculature

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation
  • Biomedical Engineering

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