Placenta-derived multipotent stem cells induced to differentiate into insulin-positive cells.
In the present study, we successfully isolated PDMSCs from human placental tissues. The RT-PCR results show that PDMSCs preserved the genetic characteristics of the primitive embryonic stage--Oct-4 and Nanog. By using serum-free medium supplemented essential growth factors and induction medium culture for 4 weeks, a monolayer of spindle-like PDMSCs gradually formed 3D spheroid bodies (SB-PDMSCs). By using real-time RT-PCR, early mRNA expressions of Pdx1, as well as the Sox17 and Foxa2 genes, were observed to be significantly activated in SB-PDMSCs, followed by the expression of mature pancreas-related genes (insulin, glucagon, and somatostatin). The high insulin content of SB-PDMSCs was further confirmed by ELISA assay, and the glucose dependency was demonstrated by the corresponding insulin secretion level. In a transplantation study of streptozotocin-pretreated nude mice, the restoration of normoglycemia in the SB-PDMSC treated group was further observed. In conclusion, these results indicate that PDMSCs are an excellent source for the induced differentiation of well-functioning insulin-positive cells. The potential of these insulin producing cells derived from PDMSCs was also demonstrated functionally by the demonstration of secreted insulin in vitro and effective control of blood glucose levels in vivo.
Chang
Chia-Ming
CM
Department of Obstetrics and Gynecology, Taipei, Taiwan.
Kao
Chung-Lan
CL
Chang
Yuh-Lih
YL
Yang
Ming-Jie
MJ
Chen
Yu-Chih
YC
Sung
Bi-Lin
BL
Tsai
Tung-Hu
TH
Chao
Kuan-Chong
KC
Chiou
Shih-Hwa
SH
Ku
Hung-Hai
HH
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000473:pathology / Q000601:surgery*; D005260:Female; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000637:transplantation*; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000637:transplantation*; D010920:Placenta / Q000166:cytology*; D023822:Tissue Engineering / Q000379:methods*; D016896:Treatment Outcome