Intrarenal arterial administration of human umbilical cord-derived mesenchymal stem cells effectively preserved the residual renal function of diabetic kidney disease in rat

Abstract

Background This experimental study was designed as a preclinical study for testing the hypothesis that intrarenal arterial (IRA) transfusion of human umbilical cord-derived mesenchymal stem cells (HUCDMSCs) therapy preserved the residual renal function of diabetic kidney disease (DKD) in rat [induction by 5/6 nephrectomy of left kidney and right nephrectomy, followed by intraperitoneal administration of aminoguanidine (180 mg/kg) and streptozotocin (30 mg/kg)]. Methods Animals (n = 24) were categorized into group 1 (sham-operated control), group 2 (DKD), group 3 [DKD + HUCDMSCs (2.1 × 105/IRA injection at day 28 after CKD induction)] and group 4 [(DKD + HUCDMSCs (6.3 × 105/IRA injection)]. Results By day 60 after DKD induction, the kidneys were harvested and the result showed that the creatinine level, ratio of urine protein/urine creatinine and kidney injury score were lowest in group 1, highest in group 2 and significantly lower in group 4 than in group 3 (all p < 0.0001). The protein expressions of apoptotic (cleaved caspase-3/cleaved PARP/mitochondrial Bax), fibrotic (TGF-ß/p-Smad3), autophagic (ratio of LC3B-II/LC3B-I, Atg5/Beclin-1), oxidative stress (NOX-1/NOX-2/oxidized protein/p22phox), mitochondrial/DNA-damaged (cytosolic-cytochrome-C/DRP1/γ-H2AX) and inflammatory (MMP-9/TNF-α/p-NF-κB) biomarkers exhibited an identical pattern, whereas the protein expressions of angiogenesis factors (CD31/vWF/vascularity) exhibited an opposite pattern of creatinine level among the groups (all p < 0.0001). Histopathological findings demonstrated the renal tubular-damaged (KIM-1)/kidney fibrosis area/oxidative stress (8-OHdG + cells) expressed an identical pattern, whereas the podocyte components (ZO-1/synaptopodin/podocin) exhibited an opposite pattern of creatinine level among the groups (all p < 0.0001). No tumorigenesis or immune rejection event was identified. Conclusion IRA injection of xenogeneic MSCs was safe and effectively protected the residual renal function and architectural integrity in DKD rat.

Oxidized-LDL Deteriorated the Renal Residual Function and Parenchyma in CKD Rat through Upregulating Epithelial Mesenchymal Transition and Extracellular Matrix-Mediated Tubulointerstitial Fibrosis—Pharmacomodulation of Rosuvastatin

“…In the present study, we found that the cellular expressions of podocyte components of ZO-1 and synaptopodin were notably reduced in CKD animals and further, remarkably reduced in oxidized LDL-treated CKD animals. Hence, our finding, besides supporting the findings of previous studies [ 32 , 42 ], could at least in part explain why the proteinuria was notably increased in CKD and further increased in oxidized LDL-treated CKD animals. Furthermore, these perturbations of podocytes and proteinuria were significantly reversed by rosuvastatin treatment in CKD + oxidized LDL animals, emphasizing again the importance of statin therapy for alleviation of progressive renal damage in the CKD setting.…”

“…Our previous study has clearly demonstrated that the integrity of podocyte components was essential for avoiding the proteinuria [ 32 , 42 ]. In the present study, we found that the cellular expressions of podocyte components of ZO-1 and synaptopodin were notably reduced in CKD animals and further, remarkably reduced in oxidized LDL-treated CKD animals.…”

Synergic Effect of Early Administration of Probiotics and Adipose-Derived Mesenchymal Stem Cells on Alleviating Inflammation-Induced Chronic Neuropathic Pain in Rodents

“…Additionally, even allogenic MSCs have been applied for patients with severe cardiovascular disease [ 31 ] or acute respiratory distress syndrome [ 32 ], and the results were reported to be safe and to have potentially improved the clinical outcomes. These findings [ 25 , 26 , 27 , 29 , 30 , 31 , 32 ] highlight that MSC therapy may possess therapeutic potential for NP patients. However, whether MSC therapy would provide benefits for NP is currently unclear.…”

“…Mesenchymal stem cells (MSCs), particularly adipose-derived MSCs (i.e., ADMSCs), have been clearly identified to possess the intrinsic ability to ameliorate inflammatory reaction [ 25 , 26 , 27 ] and inhibit innate and adaptive immunity [ 25 , 26 , 27 , 28 ] through reducing immunogenicity [ 25 , 26 , 27 ]. Additionally, abundant evidence has clearly demonstrated that MSCs have the capacity to manage antioxidative stress, perform angiogenesis, and repair damaged tissue and organs, resulting in tissue/organ regeneration as well as improvement of mitochondrial dysfunction [ 25 , 26 , 27 , 29 , 30 ]. Additionally, even allogenic MSCs have been applied for patients with severe cardiovascular disease [ 31 ] or acute respiratory distress syndrome [ 32 ], and the results were reported to be safe and to have potentially improved the clinical outcomes.…”

Recent Advances in the Management of Diabetic Kidney Disease: Slowing Progression

“…MMP-9, expressed in the proximal renal tubular epithelial cells, has been validated to regulate the degradation of the extracellular matrix during renal fibrosis [ 61 ]. The downregulation of MMP-9 can effectively slow the progression of DKD by improving creatinine and reducing proteinuria [ 62 ].…”