Human embryonic mesenchymal stem cell-derived conditioned medium rescues kidney function in rats with established chronic kidney disease.
Chronic kidney disease (CKD) is a major health care problem, affecting more than 35% of the elderly population worldwide. New interventions to slow or prevent disease progression are urgently needed. Beneficial effects of mesenchymal stem cells (MSC) have been described, however it is unclear whether the MSCs themselves or their secretome is required. We hypothesized that MSC-derived conditioned medium (CM) reduces progression of CKD and studied functional and structural effects in a rat model of established CKD. CKD was induced by 5/6 nephrectomy (SNX) combined with L-NNA and 6% NaCl diet in Lewis rats. Six weeks after SNX, CKD rats received either 50 µg CM or 50 µg non-CM (NCM) twice daily intravenously for four consecutive days. Six weeks after treatment CM administration was functionally effective: glomerular filtration rate (inulin clearance) and effective renal plasma flow (PAH clearance) were significantly higher in CM vs. NCM-treatment. Systolic blood pressure was lower in CM compared to NCM. Proteinuria tended to be lower after CM. Tubular and glomerular damage were reduced and more glomerular endothelial cells were found after CM. DNA damage repair was increased after CM. MSC-CM derived exosomes, tested in the same experimental setting, showed no protective effect on the kidney. In a rat model of established CKD, we demonstrated that administration of MSC-CM has a long-lasting therapeutic rescue function shown by decreased progression of CKD and reduced hypertension and glomerular injury.
Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, the Netherlands.
Arianne
A
van Koppen
Jaap A
JA
Joles
Bas W M
BW
van Balkom
Sai Kiang
SK
Lim
Dominique
D
de Kleijn
Rachel H
RH
Giles
Marianne C
MC
Verhaar
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D007677:Kidney Function Tests; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D007684:Kidney Tubules / Q000737:chemistry / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D050199:Podocytes / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000503:physiopathology*; D014945:Wound Healing / Q000187:drug effects
D017077:Culture Media, Conditioned; D016207:Cytokines