Cyotomedical therapy for insulinopenic diabetes using microencapsulated pancreatic beta cell lines.
Current therapy for type 1 diabetes mellitus involves a daily regimen of multiple subcutaneous or intramuscular injections of recombinant human insulin. To achieve long-term insulin delivery in vivo, we investigated the applicability of cytomedical therapy using beta TC6 cells or MIN6 cells, both of which are murine pancreatic beta cell lines that secrete insulin in a subphysiologically or physiologically regulated manner, respectively. We examined this therapy in the insulinopenic diabetic mice intraperitoneally injected with beta TC6 cells or MIN6 cells microencapsulated within alginate-poly(L)lysine-alginate membranes (APA-beta TC6 cells or APA-MIN6 cells). The diabetic mice treated with APA-beta TC6 cells fell into hypoglycemia, whereas those injected with APA-MIN6 cells maintained normal blood glucose concentrations for over 2 months without developing hypoglycemia. In addition, we also conducted an oral glucose tolerance test using these mice. The blood glucose concentrations of normal and of diabetic mice injected with APA-MIN6 cells similarly changed over time, although the blood insulin concentration increased later in the injected diabetic mice than in the former. These results suggest that cytomedicine utilizing microencapsulated pancreatic beta cell lines with a physiological glucose sensor may be a beneficial and safe therapy with which to treat diabetes mellitus.
Suzuki
Ryo
R
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Okada
Naoki
N
Miyamoto
Hajime
H
Yoshioka
Tatsunobu
T
Sakamoto
Kayoko
K
Oka
Hiroaki
H
Tsutsumi
Yasuo
Y
Nakagawa
Shinsaku
S
Miyazaki
Jun-ichi
J
Mayumi
Tadanori
T
D000464:Alginates; D000818:Animals; D001672:Biocompatible Materials; D001786:Blood Glucose / Q000378:metabolism; D002214:Capsules; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D004339:Drug Compounding; D005260:Female; D005951:Glucose Tolerance Test; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D011107:Polylysine / Q000031:analogs & derivatives*
D000464:Alginates; D001672:Biocompatible Materials; D001786:Blood Glucose; D002214:Capsules; D007328:Insulin; C051546:alginate-polylysine-alginate; D011107:Polylysine