title: Human insulin secreted from insulinogenic xenograft restores normoglycemia in type 1 diabetic mice without immunosuppression.
abstract: In the present study, we examined the therapeutic potential of human amnion-derived insulin-secreting cells for type 1 diabetes. Human amniotic mesenchymal stem cells (hAMs) were isolated from amnion and cultivated to differentiate into insulin-secreting cells in vitro. After culture  in vitro, the differentiated cells (hAM-ISCs) were intensively stained with dithizone and secreted insulin and c-peptide in a high-glucose-dependent manner. They expressed mRNAs of pancreatic cell-related genes, including INS, PDX1, Nkx6-1, NEUROG3, ISL1, NEUROD1, GLUT1, GLUT2, PC1/3, PC2,  GCK, PPY, SST, and GC, and were positive for human insulin and c-peptide. Transplantation of hAM-ISCs into the kidneys of mice with streptozotocin-induced diabetes restored body weight and normalized the blood glucose levels, which lasted for 210 days. Only human insulin and c-peptide were  detected in the blood of normalized mice after 2 months of transplantation, but little mouse insulin and c-peptide. Removal of graft-bearing kidneys from these mice resulted in causing hyperglycemia again. Human cell-specific gene, hAlu, and human pancreatic cell-specific genes, insulin, PDX1,  GLUT1, GLP1R, Nkx6-1, NEUROD1, and NEUROG3, were detected in the graft-bearing kidneys. Colocalization of human insulin and human nuclei antigen was also observed. These results demonstrate that hAMs could differentiate into functional insulin-secreting cells in vitro, and human insulin secreted  from hAM-ISCs following transplantation into type 1 diabetic mice could normalize hyperglycemia, overcoming immune rejection for a long period.
authors.affiliation: bcellbio, Inc., Seoul, South Korea.
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Park
authors.forename: H M
authors.initials: HM
authors.lastname: Kang
authors.forename: C W
authors.initials: CW
authors.lastname: Ahn
authors.forename: H C
authors.initials: HC
authors.lastname: Kwon
authors.forename: J H
authors.initials: JH
authors.lastname: Song
authors.forename: Y J
authors.initials: YJ
authors.lastname: Lee
authors.forename: K H
authors.initials: KH
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.forename: S Y
authors.initials: SY
authors.lastname: Baek
authors.forename: S H
authors.initials: SH
authors.lastname: Yoo
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
authors.forename: H
authors.initials: H
authors.lastname: Kim
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000008:administration & dosage / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000628:therapy*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000628:therapy; D007150:Immunohistochemistry; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000637:transplantation*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014183:Transplantation, Heterologous
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin