Human umbilical cord mesenchymal stem cells support nontumorigenic expansion of human embryonic stem cells.
The expansion of pluripotent human embryonic stem cells (hESCs) requires a culture on feeder layers of mouse embryonic fibroblasts (MEFs). The culture model often causes immunogenic contaminations such as xenocarbohydrate, and inevitably forms teratoma in vivo. This study tested human umbilical cord-derived mesenchymal stem cells (HUCMSCs) as the feeder for hESCs. Wharton's jelly-derived HUCMSCs showed characteristics of MSCs and were easily maintained in a culture for over 20 passages. Under the mitomycin-inhibited HUCMSC feeder, hESCs maintained the features of embryonic stem cells (pluripotency and maintenance of normal karyotypes) after a prolonged culture of more than 20 passages. Notably, in extensive trials, no teratoma was formed in xenograft in NOD/SCID mice, but subsequent resumption of teratoma formation was noted upon transient coculturing with MEFs. Interestingly, among the four pluripotency-conferring genes, MYC and OCT4 were found to be downregulated in hESCs cocultured with HUCMSCs. Results of this study supported a nontumorigenic sustained culture of hESCs and did not form teratoma in vivo.
Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan.
Dah-Ching
DC
Ding
Woei-Cherng
WC
Shyu
Shinn-Zong
SZ
Lin
Hwan-Wun
HW
Liu
Shih-Hwa
SH
Chiou
Tang-Yuan
TY
Chu
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D061252:Feeder Cells; D006801:Humans; D007621:Karyotyping; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D013724:Teratoma / Q000473:pathology; D014183:Transplantation, Heterologous; D059631:Wharton Jelly / Q000166:cytology*
D050814:Octamer Transcription Factor-3; D016271:Proto-Oncogene Proteins c-myc