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A Novel Clinical Grade Isolation Method for Human Kidney Perivascular Stromal Cells
Published on: August 7, 2017
Repeated administration of bone marrow-derived mesenchymal stem cells improved the protective effects on a remnant
Sul-Ra Lee1, Sang-Ho Lee, Ju-Young Moon
1Department of Nephrology, East-West Neo Medical Center, Kyung Hee University, Seoul, Republic of Korea.
Abstract:
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.
Insights
Repeated administration of mesenchymal stem cells (MSCs) significantly improved chronic kidney disease outcomes by reducing blood pressure and improving kidney function, primarily through paracrine effects.
Area of Science:
- Nephrology
- Regenerative Medicine
- Cell Biology
Background:
- Mesenchymal stem cells (MSCs) show therapeutic promise for chronic kidney disease (CKD).
- The precise mechanisms and optimal administration frequency of MSCs in CKD models remain unclear.
- Understanding MSCs' role is crucial for developing effective CKD treatments.
Purpose of the Study:
- To evaluate the impact of repeated versus single MSC administration in a rat remnant kidney model.
- To investigate the underlying mechanisms, including engraftment and paracrine effects, of MSC therapy in CKD.
- To compare the efficacy of MSCs with mesangial cells (MCs) in mitigating kidney injury.
Main Methods:
- MSCs were isolated, fluorescently tagged (CM-Dil), and administered intravenously to 5/6 nephrectomized rats.
- Groups included weekly MSC administration, single MSC injection, and single MC injection.
- Kidney function (SBP, proteinuria, creatinine), cellular infiltration (ED-1), glomerulosclerosis, gene expression (SRY, IL-6, IL-10), and cell engraftment were assessed.
Main Results:
- Weekly MSC administration significantly improved systolic blood pressure, reduced urinary protein, and lowered serum creatinine compared to single injections.
- Repeated MSC treatment led to greater attenuation of glomerulosclerosis and inflammatory cell infiltration.
- While MSCs showed transient engraftment and modulated cytokine expression (IL-6, IL-10), these effects were sustained only with weekly administration.
Conclusions:
- Repeated administration of MSCs offers superior protective effects against remnant kidney injury compared to single injections.
- The therapeutic benefits of MSCs in CKD are primarily mediated by paracrine mechanisms rather than cellular differentiation or long-term engraftment.
- Optimizing MSC administration frequency is critical for maximizing therapeutic efficacy in chronic kidney disease.
