TY - JOUR
T1 - Protective Effects of Human Nonrenal and Renal Stromal Cells and Their Conditioned Media in a Rat Model of Chronic Kidney Disease
AU - Imberti, Barbara
AU - Cerullo, Domenico
AU - Corna, Daniela
AU - Rota, Cinzia
AU - Locatelli, Monica
AU - Pezzotta, Anna
AU - Introna, Martino
AU - Capelli, Chiara
AU - Carminati, Claudia Elisa
AU - Rabelink, Ton J.
AU - Leuning, Danielle G.
AU - Zoja, Carlamaria
AU - Morigi, Marina
AU - Remuzzi, Giuseppe
AU - Benigni, Ariela
AU - Luyckx, Valerie
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Cinzia Rota and Monica Locatelli are recipients of fellowships from Fondazione Aiuti per la Ricerca sulle Malattie Rare (A.R.M.R.) Bergamo, Italy. Domenico Cerullo is a recipient of a fellowship from Fondazione Istituti Educativi di Bergamo, Bergamo, Italy, and of a grant from Cavalieri dell’Abbazia-Birreria Trappista N.D di Orval, Ponte S. Pietro, Bergamo, Italy. This work was partially supported by funding from the European Union’s Seventh Framework program, the STELLAR project (HEALTHF4–2012-305436). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 634086.
Publisher Copyright:
© The Author(s) 2020.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - Mesenchymal stromal cells (MSCs) are emerging as a novel therapeutic option for limiting chronic kidney disease progression. Conditioned medium (CM) containing bioactive compounds could convey similar benefits, avoiding the potential risks of cell therapy. This study compared the efficacy of nonrenal and renal cell-based therapy with the corresponding CM in rats with renal mass reduction (RMR). Infusions of human kidney stromal cells (kPSCs) and CM-kPSCs, but not umbilical cord (uc) MSCs or CM-ucMSCs, reduced proteinuria and preserved podocyte number and nephrin expression in RMR rats. Glomerular fibrosis, microvascular rarefaction, and apoptosis were reduced by all treatments, while the peritubular microvascular loss was reduced by kPSCs and CM-kPSCs treatment only. Importantly, kPSCs and CM-kPSCs reduced NG2-positive pericytes, and all therapies reduced α-smooth muscle actin expression, indicating reduced myofibroblast expansion. Treatment with kPSCs also significantly inhibited the accumulation of ED1-positive macrophages in the renal interstitium of RMR rats. These findings demonstrate that the CM of ucMSCs and kPSCs confers similar renoprotection as the cells. kPSCs and CM-kPSCs may be superior in attenuating chronic renal injury as a cell source.
AB - Mesenchymal stromal cells (MSCs) are emerging as a novel therapeutic option for limiting chronic kidney disease progression. Conditioned medium (CM) containing bioactive compounds could convey similar benefits, avoiding the potential risks of cell therapy. This study compared the efficacy of nonrenal and renal cell-based therapy with the corresponding CM in rats with renal mass reduction (RMR). Infusions of human kidney stromal cells (kPSCs) and CM-kPSCs, but not umbilical cord (uc) MSCs or CM-ucMSCs, reduced proteinuria and preserved podocyte number and nephrin expression in RMR rats. Glomerular fibrosis, microvascular rarefaction, and apoptosis were reduced by all treatments, while the peritubular microvascular loss was reduced by kPSCs and CM-kPSCs treatment only. Importantly, kPSCs and CM-kPSCs reduced NG2-positive pericytes, and all therapies reduced α-smooth muscle actin expression, indicating reduced myofibroblast expansion. Treatment with kPSCs also significantly inhibited the accumulation of ED1-positive macrophages in the renal interstitium of RMR rats. These findings demonstrate that the CM of ucMSCs and kPSCs confers similar renoprotection as the cells. kPSCs and CM-kPSCs may be superior in attenuating chronic renal injury as a cell source.
KW - chronic kidney disease
KW - conditioned medium
KW - renal perivascular cells
KW - renal repair
KW - stromal cells
UR - http://www.scopus.com/inward/record.url?scp=85098447737&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85098447737&partnerID=8YFLogxK
U2 - 10.1177/0963689720965467
DO - 10.1177/0963689720965467
M3 - Article
AN - SCOPUS:85098447737
VL - 29
JO - Cell Transplantation
JF - Cell Transplantation
SN - 0963-6897
ER -