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Stem Cell Res Ther. 2017 Feb 7;8(1):24. doi: 10.1186/s13287-017-0478-5.

The effects of glomerular and tubular renal progenitors and derived extracellular vesicles on recovery from acute kidney injury.

Author information

1
Department of Medical Sciences and Molecular Biotechnology Center, University of Torino, Corso Dogliotti 14, Torino, 10126, Italy. andrea.ranghino@unito.it.
2
Department of Molecular Biotechnology and Health Sciences and Molecular Biotechnology Center, University of Torino, Torino, Italy.
3
Department of Medical Sciences and Molecular Biotechnology Center, University of Torino, Corso Dogliotti 14, Torino, 10126, Italy.
4
Department of Surgical Sciences, Città della Salute e della Scienza, University of Turin, Torino, Italy.

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.

KEYWORDS:

Extracellular vesicles; Glomerular mesenchymal stromal cells; Ischemia-reperfusion injury; Renal regeneration

PMID:
28173878
PMCID:
PMC5297206
DOI:
10.1186/s13287-017-0478-5
[Indexed for MEDLINE]
Free PMC Article

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