Tissue Eng Regen Med.  2019 Feb;16(1):81-92. 10.1007/s13770-018-0162-6.

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

• Yu NH
• Chun SY
• Ha YS
• Kim HT
• Lih E
• Kim DH
• Kim J
• Chung JW
• Song PH
• Yoo ES
• Chung SK
• Han DK
• Kim BS
• Kwon TG

• KMID: 2441258
• DOI: http://doi.org/10.1007/s13770-018-0162-6

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 proinflammatory 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.

Keyword

Amniotic fluid stem cell; Long-term cell transportation; Tissue regeneration

MeSH Terms

Amniotic Fluid*
Blood Urea Nitrogen
Cell- and Tissue-Based Therapy
Creatinine
Cytokines
Female
In Vitro Techniques
Kidney
Liver
Lung
Polyglactin 910
Regeneration*
Spleen
Stem Cells*
Creatinine
Cytokines
Polyglactin 910