Subcutaneous transplantation of macroencapsulated porcine pancreatic endocrine cells normalizes hyperglycemia in diabetic mice.
BACKGROUND
The ultimate goal of islet transplantation is the unlimited availability of insulin-secreting cells to be transplanted in a simple procedure that requires no use of immunosuppressive drugs. Immunoisolation of xenogeneic pig islets for transplantation has great potential therapeutic benefits for treatment of diabetes.


METHODS
Approximately 4 x 10(6) porcine pancreatic endocrine cells (PEC) isolated from 6-month-old pigs were macroencapsulated in agarose-poly(styrene sulfonic acid) mixed gel and implanted into a prevascularized subcutaneous site in streptozotocin-induced C57BL/6 diabetic mice. Animals receiving an equal number of free porcine PEC were used as controls. After transplantation, nonfasting blood glucose, body weight, intraperitoneal glucose tolerance test, and immunohistologic evaluations were processed.


RESULTS
All 10 animals receiving the subcutaneous xenografts of the macroencapsulated porcine PEC normalized hyperglycemia within 5 days after transplantation, maintained the duration of normoglycemia for 24 to 76 days, and gradually gained weight. The subcutaneous xenografts of free porcine PEC could not reverse hyperglycemia. The recipient became hyperglycemic again when the implanted graft was retrieved at day 45 after transplantation. The glucose clearances were significantly ameliorated at day 21 and day 45 after transplantation when compared with those in diabetic mice. The immunohistochemical results revealed an inherent intact structure of the macroencapsulated porcine PEC and positive double-immunofluorescence staining for insulin and glucagon.


CONCLUSIONS
Subcutaneous transplantation of macroencapsulated porcine PEC normalized hyperglycemia in diabetic mice. Our results identified a potential for a favorable development of subcutaneous transplantation of porcine PEC as a cure for diabetes.
Wang
Wenjing
W
Department of Organ Reconstruction, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
Gu
Yuanjun
Y
Hori
Hiroshi
H
Sakurai
Tomonori
T
Hiura
Akihito
A
Sumi
Shoichiro
S
Tabata
Yasuhiko
Y
Inoue
Kazutomo
K
D000818:Animals; D000890:Anti-Infective Agents; D001120:Arginine / Q000494:pharmacology; D002214:Capsules; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D005782:Gels; D005947:Glucose / Q000494:pharmacology; D006085:Graft Survival; D006943:Hyperglycemia / Q000601:surgery*; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D011137:Polystyrenes; D012685:Sepharose; D040521:Subcutaneous Tissue; D013552:Swine; D013806:Theophylline / Q000494:pharmacology; D014183:Transplantation, Heterologous; D014665:Vasodilator Agents / Q000494:pharmacology
D000890:Anti-Infective Agents; D002214:Capsules; D005782:Gels; D007328:Insulin; D011137:Polystyrenes; D014665:Vasodilator Agents; C003321:polystyrene sulfonic acid; D012685:Sepharose; D001120:Arginine; D013806:Theophylline; D005947:Glucose