Induced Intermediate Mesoderm Combined with Decellularized Kidney Scaffolds for Functional Engineering Kidney
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Chronic kidney disease is a severe threat to human health with no ideal treatment strategy. Mature mammalian kidneys have a fixed number of nephrons, and regeneration is difficult once they are damaged. For this reason, developing an efficient approach to achieve kidney regeneration is necessary. The technology of the combination of decellularized kidney scaffolds with stem cells has emerged as a new strategy; however, in previous studies, the differentiation of stem cells in decellularized scaffolds was insufficient for functional kidney regeneration, and many problems remain.
We used 0.5% sodium dodecyl sulfate (SDS) to produce rat kidney decellularized scaffolds, and induce adipose-derived stem cells (ADSCs) into intermediate mesoderm by adding Wnt agonist CHIR99021 and FGF9 in vitro. The characteristics of decellularized scaffolds and intermediate mesoderm induced from adipose–derived stem cells were identified. The scaffolds were recellularized with ADSCs and intermediate mesoderm cells through the renal artery and ureter. After cocultured for 10 days, cells adhesion and differentiation was evaluated.
Intermediate mesoderm cells were successfully induced from ADSCs and identified by immunofluorescence and Western blotting assays (OSR1 + , PAX2 +). Immunofluorescence showed that intermediate mesoderm cells differentiated into tubular-like (E-CAD + , GATA3 +) and podocyte-like (WT1 +) cells with higher differentiation efficiency than ADSCs in the decellularized scaffolds. Comparatively, this phenomenon was not observed in induced intermediate mesoderm cells cultured in vitro.
In this study, we demonstrated that intermediate mesoderm cells could be induced from ADSCs and that they could differentiate well after cocultured with decellularized scaffolds.
KeywordsKidney regeneration Decellularized scaffolds Adipose-derived stem cells Intermediate mesoderm cells Induced differentiation
This work was supported by the National Nature Science Foundation of China (Grant No. 81670625, 81470969, and 81700592), Shandong Province Natural Science Foundation (ZR2017BH104; ZR2018MH006; ZR2018BH007; ZR2015PH023), and the Youth Fund and Youth Talent Fund of the Second Hospital of Shandong University (2018YT32 and Y2015010038). We are grateful to the Central Research Laboratory, the Second Hospital of Shandong University for technical assistance and generous support.
Compliance with ethical standards
Conflict of interest
All authors declare that there is no conflict of interest.
This study was approved by the Animal Ethics Committee of Shandong University [KYLL-2017(GJ)A-0011]. All surgical procedures were performed according to the Guide for the Care and Use of Laboratory Animals.