Intravenous administration of iPS‐MSC SPIONs mobilized into CKD parenchyma and effectively preserved residual renal function in CKD rat

This study traced intravenously administered induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (MSC) and assessed the impact of iPSC-MSC on preserving renal function in SD rat after 5/6 nephrectomy. The results of in vitro study showed that FeraTrackDirect contrast particles (ie intracellular magnetic labelling) in the iPSC-MSC (ie iPS-MSC(SPIONs) ) were clearly identified by Prussian blue stain. Adult-male SD rats (n = 40) were categorized into group 1 (SC), group 2 [SC + iPS-MSC(SPIONs) (1.0 x 10(6) cells)/intravenous administration post-day-14 CKD procedure], group 3 (CKD), group 4 [CKD + iPS-MSC(SPIONs) (0.5 x 10(6) cells)] and group 5 [CKD + iPS-MSC(SPIONs) (1.0 x 10(6) cells)]. By day-15 after CKD induction, abdominal MRI demonstrated that iPS-MSC(SPIONs) were only in the CKD parenchyma of groups 4 and 5. By day 60, the creatinine level/ratio of urine protein to urine creatinine/kidney injury score (by haematoxylin and eosin stain)/fibrotic area (Masson's trichrome stain)/IF microscopic finding of kidney injury molecule-1 expression was lowest in groups 1 and 2, highest in group 3, and significantly higher in group 4 than in group 5, whereas IF microscopic findings of podocyte components (ZO-1/synaptopodin) and protein levels of anti-apoptosis ((Bad/Bcl-xL/Bcl-2) exhibited an opposite pattern to creatinine level among the five groups (all P < .0001). The protein expressions of cell-proliferation signals (PI3K/p-Akt/m-TOR, p-ERK1/2, FOXO1/GSK3beta/p90RSK), apoptotic/DNA-damage (Bax/caspases8-10/cytosolic-mitochondria) and inflammatory (TNF-alpha/TNFR1/TRAF2/NF-kappaB) biomarkers displayed an identical pattern to creatinine level among the five groups (all P < .0001). The iPS-MSC(SPIONs) that were identified only in CKD parenchyma effectively protected the kidney against CKD injury.