NDLI: Dose optimization of tacrolimus for improving survival time of PEGylated islets in a rat-to-mouse xenograft model

Content Provider	Springer Nature Link
Author	Jeong, Jee Heon Yook, Simmyung Byun, Youngro
Copyright Year	2016
Abstract	Improvements in preventing pancreatic islet rejection are needed for successful treatment of type 1 diabetes. Our objective was to develop an optimized protocol combining modification of islets with polyethyleneglycol (PEG) chains and administration of tacrolimus (FK506, Prograf), an immunosuppressive drug for preventing rejection following transplantation. Freshly isolated islets were incubated with different concentrations (0.25, 1.00, 10.00, and 25.00%) of FITC-labeled mPEG-SCM (MW. 20 KDa) for various incubation times. 1% mPEG-SCM incubated with islets for 1 h is optimized surface coverage condition without cell toxicity. In addition, in order to optimize the concentration of tacrolimus (FK506, Prograf), different concentrations (0.1, 0.5 or 2.0 mg/kg) were injected into the diabetic mice following transplantation of PEGylated islets. The PEGylated islet survival time in mice injected daily with 0.1 mg/kg and 0.5 mg/kg of tacrolimus was significantly better than in the group without tacrolimus injection. The graft survival time in mice injected daily with 2.00 mg/kg of exhibited no prolonged survival time. Finally, immunohistochemical staining of left kidney containing PEGylated islets (injected with 0.1 mg/kg of tacrolimus) demonstrated strong staining for insulin, glucagon, and somatostatin but very weak CD20 staining was observed in the islet transplanted area. In conclusion, 1% mPEG-SCM incubated with islets for 1 h was the optimal condition for PEGylation without affecting the cell viability. A dose of tacrolimus between 0.1-0.5 mg/kg was highly effective for inhibiting immune cell activation. These results are promising for their application in developing a novel immunosuppressive protocol for successful pancreatic islet transplantation in the treatment of type 1 diabetes.
Starting Page	1047
Ending Page	1054
Page Count	8
File Format	PDF
ISSN	15985032
Journal	Macromolecular Research
Volume Number	24
Issue Number	12
e-ISSN	20927673
Language	English
Publisher	The Polymer Society of Korea
Publisher Date	2016-08-24
Publisher Place	Seoul
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	islet transplantation FK506 PEGylation surface modification Polymer Sciences Soft and Granular Matter, Complex Fluids and Microfluidics Physical Chemistry Characterization and Evaluation of Materials Nanochemistry Nanotechnology
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Materials Chemistry Chemical Engineering Polymers and Plastics

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