Repeated administration of bone marrow-derived mesenchymal stem cells improved the protective effects on a remnant kidney model.
Mesenchymal stem cell (MSC) has been implied to have the therapeutic potential on chronic kidney disease (CKD). However, the underlying mechanism is still unclear and administration frequency of MSCs could be an issue in a chronic disease model. We evaluated the effect of repeated administration of MSCs on a remnant kidney model. MSCs from 5-week male Sprague-Dawley rats were infused by tail vein into 7-week female 5/6 nephrectomized rats after tagging with a fluorescent probe, chloromethyl-1,1-dioctadecyl-3,3,3',3'-tetramethyl- indocarbocyanine perchlorate (CM-Dil). Effect of weekly administration of MSCs was compared with the effect of once injection of MSCs and mesangial cells (MCs) at 1 and 5 weeks, respectively. Engraftment of MSCs into the kidney was evaluated by the presence of CM-Dil fluorescence or SRY gene expression. Weekly MSCs administration showed significant improvement in systolic blood pressure (SBP), urinary protein excretion amount, and serum creatinine level at 5 weeks, whereas once MSCs or MCs administration did not. Although once MSCs administration attenuated glomerulosclerosis and infiltration of ED-1 positive cells at 5 weeks as compared with MCs, weekly MSC administration led to a more significant improvement. Renal SRY gene expression and presence of CM-Dil-tagged cells could be confirmed at 1 week after injection of MSCs or weekly injected group, but not at 5 weeks after once injection. MSCs attenuated cortical expression of interleukin (IL)-6 and elevated the expression of IL-10, but these effects were only sustained in the weekly group. Thus, repeated administration of MSCs improves the protective effect on remnant kidney injury, but primarily via the paracrine effect rather than differentiation.
Lee
Sul-Ra
SR
Department of Nephrology, East-West Neo Medical Center, Kyung Hee University, Seoul, Republic of Korea.
Lee
Sang-Ho
SH
Moon
Ju-Young
JY
Park
Ji-Yeung
JY
Lee
Dongyoung
D
Lim
Sung Jig
SJ
Jeong
Kyung-Hwan
KH
Park
Jae-Kyung
JK
Lee
Tae-Won
TW
Ihm
Chun-Gyoo
CG
D000818:Animals; D001854:Bone Marrow Cells; D002908:Chronic Disease; D005260:Female; D007674:Kidney Diseases / Q000517:prevention & control*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods* / Q000706:statistics & numerical data; D051381:Rats; D017207:Rats, Sprague-Dawley