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In Vivo Safety and Regeneration of Long-Term Transported Amniotic Fluid Stem Cells for Renal Regeneration

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

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.

Methods:

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.

Results:

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.

Conclusion:

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.

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Acknowledgements

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).

Author information

Author notes

  1. Na-hee Yu and So Young Chun authors have contributed equally to this work.

  2. Bum Soo Kim and Tae Gyun Kwon have contributed equally to this work as co-corresponding authors.

Authors and Affiliations

  1. BioMedical Research Institute, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu, 41944, Republic of Korea

    Na-hee Yu & So Young Chun

  2. Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu, 41944, Republic of Korea

    Yun-Sok Ha, Eun Sang Yoo, Sung Kwang Chung & Bum Soo Kim

  3. Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, 807 Hoguk-ro, Buk-gu, Daegu, 41404, Republic of Korea

    Hyun Tae Kim, Jae-Wook Chung & Tae Gyun Kwon

  4. Department of Biomedical Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi, 13488, Republic of Korea

    Eugene Lih & Dong Keun Han

  5. Department of Laboratory Animal Research Support Team, Yeungnam University Medical Center, 170 hyunchung-ro, Nam-gu, Daegu, 42415, Republic of Korea

    Dae Hwan Kim

  6. Department of Pathology, Central Hospital, 480 Munsu-ro, Nam-gu, Ulsan, 44667, Republic of Korea

    Jeongshik Kim

  7. Department of Urology, College of Medicine, Yeungnam University, 170 Hyunchung-ro, Nam-gu, Daegu, 42415, Republic of Korea

    Phil Hyun Song

Authors
  1. Na-hee Yu
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  2. So Young Chun
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  3. Yun-Sok Ha
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  4. Hyun Tae Kim
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  5. Eugene Lih
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  6. Dae Hwan Kim
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  7. Jeongshik Kim
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  8. Jae-Wook Chung
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  9. Phil Hyun Song
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  10. Eun Sang Yoo
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  11. Sung Kwang Chung
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  12. Dong Keun Han
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  13. Bum Soo Kim
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  14. Tae Gyun Kwon
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Corresponding authors

Correspondence to Bum Soo Kim or Tae Gyun Kwon.

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Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical statement

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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Cite this article

Yu, Nh., Chun, S.Y., Ha, YS. et al. In Vivo Safety and Regeneration of Long-Term Transported Amniotic Fluid Stem Cells for Renal Regeneration. Tissue Eng Regen Med 16, 81–92 (2019). https://doi.org/10.1007/s13770-018-0162-6

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  • DOI: https://doi.org/10.1007/s13770-018-0162-6

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