In Vivo Safety and Regeneration of Long-Term Transported Amniotic Fluid Stem Cells for Renal Regeneration
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Despite major progress in stem cell therapy, our knowledge of the characteristics and tissue regeneration potency of long-term transported cells is insufficient. In a previous in vitro study, we established the optimal cell transport conditions for amniotic fluid stem cells (AFSCs). In the present study, the target tissue regeneration of long-term transported cells was validated in vivo.
For renal regeneration, transported AFSCs were seeded on a poly(lactide-co-glycolide) scaffold and implanted in a partially resected kidney. The target tissue regeneration of the transported cells was compared with that of freshly harvested cells in terms of morphological reconstruction, histological microstructure reformation, immune cell infiltration, presence of induced cells, migration into remote organs, expression of inflammation/fibrosis/renal differentiation-related factors, and functional recovery.
The kidney implanted with transported cells showed recovery of total kidney volume, regeneration of glomerular/renal tubules, low CD4/CD8 infiltration, and no occurrence of cancer during 40 weeks of observation. The AFSCs gradually disappeared and did not migrate into the liver, lung, or spleen. We observed low expression levels of pro-inflammatory cytokines and fibrotic factors; enhanced expression of the genes Wnt4, Pax2, Wt1, and Emx2; and significantly reduced blood urea nitrogen and creatinine values. There were no statistical differences between the performance of freshly harvested cells and that of the transported cells.
This study demonstrates that long-term transported cells under optimized conditions can be used for cell therapy without adverse effects on stem cell characteristics, in vivo safety, and tissue regeneration potency.
KeywordsAmniotic fluid stem cell Long-term cell transportation Tissue regeneration
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) & funded by the Korean government (MSIT) (2014M3A9D3034164), (2015R1C1A1A01053509) (2016R1C1B1011180) (2018R1C1B5040264), and the Ministry of Trade, Industry and Energy (R0005886).
Compliance with ethical standards
Conflicts of interest
The authors declare that they have no conflict of interest.
This study was approved by the Ethics Committee of Kyungpook National University School of Medicine and all in vivo experimental protocols were approved by the Yeungnam University Institutional Animal Care and Use Committee (YUMC-AEC2015-003).
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