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

摘要

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 FeraTrack?Direct 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?×?10 6 cells)/intravenous administration post‐day‐14 CKD procedure], group 3 (CKD), group 4 [CKD + iPS‐MSC SPIONs (0.5?×?10 6 cells)] and group 5 [CKD + iPS‐MSC SPIONs (1.0?×?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/GSK3β/p90RSK), apoptotic/DNA‐damage (Bax/caspases8‐10/cytosolic‐mitochondria) and inflammatory (TNF‐α/TNFR1/TRAF2/NF‐κB) 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.