Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice.
Embryonic stem (ES) cells display the ability to differentiate in vitro into a variety of cell lineages. Using a cell-trapping system, we have obtained an insulin-secreting cell clone from undifferentiated ES cells. The construction used allows the expression of a neomycin selection system under the control of the regulatory regions of the human insulin gene. The chimeric gene also contained a hygromycin resistance gene (pGK-hygro) to select transfected cells. A resulting clone (IB/3x-99) containing 16.5 ng/microg protein of total insulin displays regulated hormone secretion in vitro in the presence of various secretagogues. Clusters obtained from this clone were implanted (1 x 10(6) cells) in the spleen of streptozotocin-induced diabetic animals. Transplanted animals correct hyperglycemia within 1 week and restore body weight in 4 weeks. Whereas an intraperitoneal glucose tolerance test showed a slower recovery in transplanted versus control mice, blood glucose normalization after a challenge meal was similar. This approach opens new possibilities for tissue transplantation in the treatment of type 1 and type 2 diabetes and offers an alternative to gene therapy.
Soria
B
B
Institute of Bioengineering, Universidad Miguel Hernandez, San Juan, Alicante, Spain. bernat.soria@umh.es
Roche
E
E
Berná
G
G
León-Quinto
T
T
Reig
J A
JA
Martín
F
F
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002999:Clone Cells; D003584:Cytological Techniques; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000601:surgery*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D051379:Mice / Q000196:embryology; D013154:Spleen / Q000601:surgery; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*
D001786:Blood Glucose; D007328:Insulin