PMID- 26882313 OWN - NLM STAT- MEDLINE DCOM- 20160725 LR - 20181202 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 11 IP - 2 DP - 2016 TI - Development of a Xeno-Free Feeder-Layer System from Human Umbilical Cord Mesenchymal Stem Cells for Prolonged Expansion of Human Induced Pluripotent Stem Cells in Culture. PG - e0149023 LID - 10.1371/journal.pone.0149023 [doi] LID - e0149023 AB - Various feeder layers have been extensively applied to support the prolonged growth of human pluripotent stem cells (hPSCs) for in vitro cultures. Among them, mouse embryonic fibroblast (MEF) and mouse fibroblast cell line (SNL) are most commonly used feeder cells for hPSCs culture. However, these feeder layers from animal usually cause immunogenic contaminations, which compromises the potential of hPSCs in clinical applications. In the present study, we tested human umbilical cord mesenchymal stem cells (hUC-MSCs) as a potent xeno-free feeder system for maintaining human induced pluripotent stem cells (hiPSCs). The hUC-MSCs showed characteristics of MSCs in xeno-free culture condition. On the mitomycin-treated hUC-MSCs feeder, hiPSCs maintained the features of undifferentiated human embryonic stem cells (hESCs), such as low efficiency of spontaneous differentiation, stable expression of stemness markers, maintenance of normal karyotypes, in vitro pluripotency and in vivo ability to form teratomas, even after a prolonged culture of more than 30 passages. Our study indicates that the xeno-free culture system may be a good candidate for growth and expansion of hiPSCs as the stepping stone for stem cell research to further develop better and safer stem cells. FAU - Zou, Qing AU - Zou Q AD - Research Center for Stem Cell and Regenerative Medicine, Sichuan Neo-life Stem Cell Biotech INC., Chengdu, Sichuan, China. AD - Center for Stem Cell Research & Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, Sichuan, China. FAU - Wu, Mingjun AU - Wu M AD - Research Center for Stem Cell and Regenerative Medicine, Sichuan Neo-life Stem Cell Biotech INC., Chengdu, Sichuan, China. FAU - Zhong, Liwu AU - Zhong L AD - Research Center for Stem Cell and Regenerative Medicine, Sichuan Neo-life Stem Cell Biotech INC., Chengdu, Sichuan, China. FAU - Fan, Zhaoxin AU - Fan Z AD - Research Center for Stem Cell and Regenerative Medicine, Sichuan Neo-life Stem Cell Biotech INC., Chengdu, Sichuan, China. FAU - Zhang, Bo AU - Zhang B AD - Research Center for Stem Cell and Regenerative Medicine, Sichuan Neo-life Stem Cell Biotech INC., Chengdu, Sichuan, China. FAU - Chen, Qiang AU - Chen Q AD - Research Center for Stem Cell and Regenerative Medicine, Sichuan Neo-life Stem Cell Biotech INC., Chengdu, Sichuan, China. AD - Center for Stem Cell Research & Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, Sichuan, China. FAU - Ma, Feng AU - Ma F AD - Research Center for Stem Cell and Regenerative Medicine, Sichuan Neo-life Stem Cell Biotech INC., Chengdu, Sichuan, China. AD - Center for Stem Cell Research & Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, Sichuan, China. AD - State Key Laboratory of Experimental Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. AD - State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160216 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Biomarkers) RN - 0 (Homeodomain Proteins) RN - 0 (Kruppel-Like Transcription Factors) RN - 0 (MYC protein, human) RN - 0 (NANOG protein, human) RN - 0 (Nanog Homeobox Protein) RN - 0 (Nucleic Acid Synthesis Inhibitors) RN - 0 (Octamer Transcription Factor-3) RN - 0 (POU5F1 protein, human) RN - 0 (Proto-Oncogene Proteins c-myc) RN - 0 (SOX2 protein, human) RN - 0 (SOXB1 Transcription Factors) RN - 0 (ZFP42 protein, human) RN - 50SG953SK6 (Mitomycin) SB - IM MH - Biomarkers/metabolism MH - Cell Differentiation/drug effects MH - Coculture Techniques MH - Embryonic Stem Cells/*cytology/metabolism MH - Feeder Cells/cytology/drug effects/metabolism MH - Fetal Blood/*cytology/drug effects/metabolism MH - Gene Expression MH - Homeodomain Proteins/genetics/metabolism MH - Humans MH - Induced Pluripotent Stem Cells/*cytology/drug effects/metabolism MH - Karyotype MH - Kruppel-Like Transcription Factors/genetics/metabolism MH - Mesenchymal Stem Cells/*cytology/drug effects/metabolism MH - Mitomycin/pharmacology MH - Nanog Homeobox Protein MH - Nucleic Acid Synthesis Inhibitors/pharmacology MH - Octamer Transcription Factor-3/genetics/metabolism MH - Proto-Oncogene Proteins c-myc/genetics/metabolism MH - SOXB1 Transcription Factors/genetics/metabolism MH - Teratoma/pathology PMC - PMC4755601 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2016/02/18 06:00 MHDA- 2016/07/28 06:00 PMCR- 2016/02/16 CRDT- 2016/02/17 06:00 PHST- 2015/11/04 00:00 [received] PHST- 2016/01/26 00:00 [accepted] PHST- 2016/02/17 06:00 [entrez] PHST- 2016/02/18 06:00 [pubmed] PHST- 2016/07/28 06:00 [medline] PHST- 2016/02/16 00:00 [pmc-release] AID - PONE-D-15-48334 [pii] AID - 10.1371/journal.pone.0149023 [doi] PST - epublish SO - PLoS One. 2016 Feb 16;11(2):e0149023. doi: 10.1371/journal.pone.0149023. eCollection 2016.