Tissue Eng Regen Med.
2019 Oct;16(5):501-512. 10.1007/s13770-019-00197-9.
Induced Intermediate Mesoderm Combined with Decellularized Kidney Scaffolds for Functional Engineering Kidney
- Affiliations
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- 1Department of Urology, The Second Hospital, Shandong University, 247 Beiyuan Street, Jinan 250033, Shandong, People's Republic of China. guanyongsdu@163.com, zhaoshengtian@sdu.edu.cn
- 2Department of Central Research Lab, The Second Hospital, Shandong University, 247 Beiyuan Street, Jinan 250033, Shandong, People's Republic of China.
- 3Key Laboratory for Kidney Regeneration of Shandong Province, 247 Beiyuan Street, Jinan 250033, Shandong, People's Republic of China.
- 4Shandong University- Karolinska Institutet Collaborative Laboratory for Stem Cell Research, 247 Beiyuan Street, Jinan 250033, Shandong, People's Republic of China.
- 5The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 16369 Jingshi Road, Jinan 250011, Shandong, People's Republic of China.
- KMID: 2464070
- DOI: http://doi.org/10.1007/s13770-019-00197-9
Abstract
- BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
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