Autologous transplantation of mesenchymal stromal cells tends to prevent progress of interstitial fibrosis in a rhesus Macaca mulatta monkey model of chronic kidney disease.
OBJECTIVE
Chronic kidney disease (CKD) attributed to cisplatin is well documented. Mesenchymal stromal cells (MSCs) are proven to be renotropic. Although they have been shown to improve function in CKD and reduce fibrosis in different experimental rodent models, their efficiency in primates is unknown. The present study aimed to evaluate the prevention of CKD and reduction of fibrosis in monkeys treated with MSCs after cisplatin nephrotoxicity.


METHODS
We induced CKD in adult rhesus Macaca mulatta monkeys by means of intravenous administration of cisplatin. Autologous MSCs were transplanted by means of intrarenal arterial injections to assess the adverse effects of cisplatin in two CKD models: preventative and stable. Preventative CKD monkeys (n = 3) underwent cell transplantation 4 days after the cisplatin injection. The stable CKD monkeys (n = 2) underwent cell transplantation 6 months after the cisplatin injection. Non-treated (n = 4) and normal saline-injected animals (n = 3) comprised the control and vehicle groups, respectively. We followed the animals for survival rate, serum biochemistry, urine analysis and histopathological indices.


RESULTS
In the preventive CKD model, MSC transplantation tended to improve some renal functions but significantly reduced the histopathologic score compared with the vehicle and control groups. In the stable CKD model, MSCs did not ameliorate renal function or pathological score.


CONCLUSIONS
These results suggest that MSCs tend to delay progression of CKD and fibrosis but do not reduce established interstitial fibrosis in this unique primate model of cisplatin-induced nephrotoxicity.
Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Reza
R
Moghadasali
Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Mostafa
M
Hajinasrollah
Urology and Nephrology Research Center, Modares Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Hassan
H
Argani
Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
Seyed Mahdi
SM
Nassiri
Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Mostafa
M
Najarasl
Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Niloofar
N
Sodeifi
Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran.
Hossein
H
Baharvand
Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. Electronic address: Nasser.Aghdami@RoyanInstitute.org.
Nasser
N
Aghdami
D000818:Animals; D002945:Cisplatin / Q000009:adverse effects; D004195:Disease Models, Animal; D005355:Fibrosis / Q000517:prevention & control / Q000628:therapy; D007668:Kidney / Q000473:pathology; D008253:Macaca mulatta; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control* / Q000628:therapy; D015996:Survival Rate; D014182:Transplantation, Autologous
D002945:Cisplatin
bone marrow mesenchymal stromal cells; chronic kidney disease; cisplatin; fibrosis; intra-renal arterial injection