Transplantation of insulin-producing cells derived from umbilical cord stromal mesenchymal stem cells to treat NOD mice.
Diabetes mellitus can be treated with islet transplantation, although there is a scarcity of donors. This study investigated whether human mesenchymal stem cells (MSCs) from umbilical cord stroma could be induced to differentiate into insulin-producing cells and the effects of retro-orbital injection of human insulin-producing cells for the treatment of nonobese diabetic (NOD) mice. MSCs were isolated from human umbilical cord stroma and induced to differentiate into insulin-producing cells using differentiation medium. Differentiated cells were evaluated by immunocytochemistry, RT-PCR, and real-time PCR. C-peptide release, both spontaneous and after glucose challenge, was measured by ELISA. Insulin-producing cells were then transplanted into NOD mice. Blood glucose levels and body weights were monitored weekly. Human nuclei and C-peptide were detected in mouse livers by immunohistochemistry. Pancreatic β-cell development-related genes were expressed in the differentiated insulin-producing cells. Differentiated cells' C-peptide release in vitro increased after glucose challenge. Further, in vivo glucose tolerance tests showed that blood sugar levels decreased after the cells' transplantation into NOD mice. After transplantation, insulin-producing cells containing human C-peptide and human nuclei were located in the liver. Thus, we demonstrated that differentiated insulin-producing cells from human umbilical cord stromal MSCs transplanted into NOD mice could alleviate hyperglycemia in diabetic mice.
Wang
Hwai-Shi
HS
Institute of Anatomy and Cell Biology, School of Medicine, National Yang Ming University, Taipei, Taiwan, ROC.
Shyu
Jia-Fwu
JF
Shen
Wen-Sheng
WS
Hsu
Hsin-Chi
HC
Chi
Torng-Chien
TC
Chen
Chie-Pein
CP
Huang
Seng-Wong
SW
Shyr
Yi-Ming
YM
Tang
Kam-Tsun
KT
Chen
Tien-Hua
TH
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000032:analysis; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D004195:Disease Models, Animal; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000637:transplantation*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D016688:Mice, Inbred NOD; D017154:Stromal Cells / Q000166:cytology; D014470:Umbilical Cord / Q000166:cytology*
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005947:Glucose