Mesenchymal stem cells as a therapeutic approach to glomerular diseases: benefits and risks

Abstract

Most studies using adult stem cells (ASCs) and progenitor cells as potential therapeutics for kidney disorders have been conducted in models of acute kidney injury, where the damage mainly affects the tubulointerstitium. The results are promising, whereas the underlying mechanisms are still being discussed controversially. Glomerular diseases have not received as much attention. Likely reasons include the often insidious onset, rendering the choice of optimal treatment timing difficult, and the fact that chronic diseases may require long-term therapy. In this mini review, we summarize current strategies in adult stem cell-based therapies for glomerular diseases. In addition, we focus on possible side effects of stem cell administration that have been reported recently, that is, profibrotic actions and maldifferentiation of mesenchymal stem cells.

Keywords: cell-based therapy; chronic kidney disease; glomerulonephritis; mesenchymal stem cell(s); progenitors; renal regeneration.

Figure 1

Evidence for intraglomerular maldifferentiation of mesenchymal stem cells (MSCs) in Lewis rats with anti-Thy1.1 nephritis on day 60 after disease induction, day 58 after injection of 2 × 10⁶ cells into the renal artery and recruitment of parietal epithelial cells during development. (a) Periodic acid-Schiff staining exhibited ‘vacuolar' changes (^*) that were positive for triglycerides in Oil Red O staining (not shown). (b) Staining for collagen type IV shows an intense fibrotic area (arrow) around the ‘vacuoles'. Original magnification: × 400. (c) Recruitment of podocytes from parietal cells in juvenile mice Cre recombination was induced in newborn triple transgenic PEC-rtTA/LC1/R26R mice by administration of doxycyclin for 3 days. After 6 weeks, the mice were culled and the glomeruli were double-stained with an enzymatic X-gal (blue)/eosin (red) staining to visualize genetically tagged cells. As expected, parietal cells lining the inner side of Bowman's capsule were genetically tagged (black arrowheads). Close to the vascular pole, genetically tagged transitional cells could be identified (arrow with tails). On the capillary convolute, a genetically tagged podocyte can be seen (arrow), which was recruited from parietal cells.