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Cheng-Lin Sun  (Sun CL) 1 Article
Repeated Gene Transfection Impairs the Engraftment of Transplanted Porcine Neonatal Pancreatic Cells
Min Koo Seo, Cheng-Lin Sun, Ji-Won Kim, Kun-Ho Yoon, Suk Kyeong Lee
Diabetes Metab J. 2011;35(1):72-79.   Published online February 28, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.1.72
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  • 3 Crossref
AbstractAbstract PDFPubReader   
Background

Previously, we reported that neonatal porcine pancreatic cells transfected with hepatocyte growth factor (HGF) gene in an Epstein-Barr virus (EBV)-based plasmid (pEBVHGF) showed improved proliferation and differentiation compared to those of the control. In this study, we examined if pancreatic cells transfected repeatedly with pEBVHGF can be successfully grafted to control blood glucose in a diabetes mouse model.

Methods

Neonatal porcine pancreatic cells were cultured as a monolayer and were transfected with pEBVHGF every other day for a total of three transfections. The transfected pancreatic cells were re-aggregated and transplanted into kidney capsules of diabetic nude mice or normal nude mice. Blood glucose level and body weight were measured every other day after transplantation. The engraftment of the transplanted cells and differentiation into beta cells were assessed using immunohistochemistry.

Results

Re-aggregation of the pancreatic cells before transplantation improved engraftment of the cells and facilitated neovascularization of the graft. Right before transplantation, pancreatic cells that were transfected with pEBVHGF and then re-aggregated showed ductal cell marker expression. However, ductal cells disappeared and the cells underwent fibrosis in a diabetes mouse model two to five weeks after transplantation; these mice also did not show controlled blood glucose levels. Furthermore, pancreatic cells transplanted into nude mice with normal blood glucose showed poor graft survival regardless of the type of transfected plasmid (pCEP4, pHGF, or pEBVHGF).

Conclusion

For clinical application of transfected neonatal porcine pancreatic cells, further studies are required to develop methods of overcoming the damage for the cells caused by repeated transfection and to re-aggregate them into islet-like structures.

Citations

Citations to this article as recorded by  
  • Successful xenotransplantation with re‐aggregated and encapsulated neonatal pig liver cells for treatment of mice with acute liver failure
    Dong‐Sik Ham, Min‐Sang Song, Heon‐Seok Park, Marie Rhee, Hae Kyung Yang, Seung‐Hwan Lee, Ji‐Won Kim, Eun‐Sun Jung, Kun‐Ho Yoon
    Xenotransplantation.2015; 22(4): 249.     CrossRef
  • Glycated Albumin Causes Pancreatic β-Cells Dysfunction Through Autophagy Dysfunction
    Young Mi Song, Sun Ok Song, Young-Hye You, Kun-Ho Yoon, Eun Seok Kang, Bong Soo Cha, Hyun Chul Lee, Ji-Won Kim, Byung-Wan Lee
    Endocrinology.2013; 154(8): 2626.     CrossRef
  • Prevalence, Awareness, and Control of Hypertension among Diabetic Koreans
    Hyun Hee Chung, Kyu Chang Won
    Diabetes & Metabolism Journal.2011; 35(4): 337.     CrossRef

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