The effects of glomerular and tubular renal progenitors and derived extracellular vesicles on recovery from acute kidney injury. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Ranghino, Andrea; Bruno, Stefania; Bussolati, Benedetta; Moggio, Aldo; Dimuccio, Veronica; Tapparo, Marta; Biancone, Luigi; Gontero, Paolo; Frea, Bruno; Camussi, Giovanni
• Is Part Of: Stem cell research & therapy. Volume 8:Issue 1(2017)
• Page Start: 1
• Page End: 15
• Publication Date: 2017-12
• Subjects: Glomerular mesenchymal stromal cells -- Extracellular vesicles -- Ischemia-reperfusion injury -- Renal regeneration; Stem cells -- Research -- Periodicals; Cellular therapy -- Periodicals; 616.0277405
• DOI: 10.1186/s13287-017-0478-5
• Languages: English
• ISSNs: 1757-6512

Abstract

Abstract Background Mesenchymal stromal cells (MSCs) and renal stem/progenitors improve the recovery of acute kidney injury (AKI) mainly through the release of paracrine mediators including the extracellular vesicles (EVs). Several studies have reported the existence of a resident population of MSCs within the glomeruli (Gl-MSCs). However, their contribution towards kidney repair still remains to be elucidated. The aim of the present study was to evaluate whether Gl-MSCs and Gl-MSC-EVs promote the recovery of AKI induced by ischemia-reperfusion injury (IRI) in SCID mice. Moreover, the effects of Gl-MSCs and Gl-MSC-EVs were compared with those of CD133+ progenitor cells isolated from human tubules of the renal cortical tissue (T-CD133+ cells) and their EVs (T-CD133+ -EVs). Methods IRI was performed in mice by clamping the left renal pedicle for 35 minutes together with a right nephrectomy. Immediately after reperfusion, the animals were divided in different groups to be treated with: Gl-MSCs, T-CD133+ cells, Gl-MSC-EVs, T-CD133+ -EVs or vehicle. To assess the role of vesicular RNA, EVs were either isolated by floating to avoid contamination of non-vesicles-associated RNA or treated with a high dose of RNase. Mice were sacrificed 48 hours after surgery. Results Gl-MSCs, and Gl-MSC-EVs both ameliorate kidney function and reduce the ischemic damage post IRI by activating tubular epithelial cell proliferation. Furthermore, T-CD133+ cells, but not their EVs, also significantly contributed to the renal recovery after IRI compared to the controls. Floating EVs were effective while RNase-inactivated EVs were ineffective. Analysis of the EV miRnome revealed that Gl-MSC-EVs selectively expressed a group of miRNAs, compared to EVs derived from fibroblasts, which were biologically ineffective in IRI. Conclusions In this study, we demonstrate that Gl-MSCs may contribute in the recovery of mice with AKI induced by IRI primarily through the release of EVs.