PMID- 25069776 OWN - NLM STAT- MEDLINE DCOM- 20160106 LR - 20211021 IS - 2157-6564 (Print) IS - 2157-6580 (Electronic) IS - 2157-6564 (Linking) VI - 3 IP - 9 DP - 2014 Sep TI - Overexpression of polysialylated neural cell adhesion molecule improves the migration capacity of induced pluripotent stem cell-derived oligodendrocyte precursors. PG - 1100-9 LID - 10.5966/sctm.2014-0041 [doi] AB - Cell replacement therapy aiming at the compensation of lost oligodendrocytes and restoration of myelination in acquired or congenital demyelination disorders has gained considerable interest since the discovery of induced pluripotent stem cells (iPSCs). Patient-derived iPSCs provide an inexhaustible source for transplantable autologous oligodendrocyte precursors (OPCs). The first transplantation studies in animal models for demyelination with iPSC-derived OPCs demonstrated their survival and remyelinating capacity, but also revealed their limited migration capacity. In the present study, we induced overexpression of the polysialylating enzyme sialyltransferase X (STX) in iPSC-derived OPCs to stimulate the production of polysialic acid-neuronal cell adhesion molecules (PSA-NCAMs), known to promote and facilitate the migration of OPCs. The STX-overexpressing iPSC-derived OPCs showed a normal differentiation and maturation pattern and were able to downregulate PSA-NCAMs when they became myelin-forming oligodendrocytes. After implantation in the demyelinated corpus callosum of cuprizone-fed mice, STX-expressing iPSC-derived OPCs demonstrated a significant increase in migration along the axons. Our findings suggest that the reach and efficacy of iPSC-derived OPC transplantation can be improved by stimulating the OPC migration potential via specific gene modulation. CI - (c)AlphaMed Press. FAU - Czepiel, Marcin AU - Czepiel M AD - Department of Neuroscience, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands. FAU - Leicher, Lasse AU - Leicher L AD - Department of Neuroscience, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands. FAU - Becker, Katja AU - Becker K AD - Department of Neuroscience, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands. FAU - Boddeke, Erik AU - Boddeke E AD - Department of Neuroscience, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands. FAU - Copray, Sjef AU - Copray S AD - Department of Neuroscience, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands j.c.v.m.copray@umcg.nl. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140728 PL - England TA - Stem Cells Transl Med JT - Stem cells translational medicine JID - 101578022 RN - 0 (Neural Cell Adhesion Molecules) RN - EC 2.4.99.- (CMP-N-acetylneuraminate-poly-alpha-2,8-sialosyl sialyltransferase) RN - EC 2.4.99.- (Sialyltransferases) SB - IM MH - Animals MH - Blotting, Western MH - Cell Differentiation/physiology MH - Cell Movement/*physiology MH - Coculture Techniques MH - Demyelinating Diseases/pathology MH - Disease Models, Animal MH - Immunohistochemistry MH - Induced Pluripotent Stem Cells/*cytology/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Neural Cell Adhesion Molecules/*biosynthesis MH - Neural Stem Cells/*cytology/metabolism MH - Oligodendroglia/*cytology/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Sialyltransferases/genetics/metabolism MH - Stem Cell Transplantation/methods MH - Transfection PMC - PMC4149301 OTO - NOTNLM OT - Cell transplantation OT - Differentiation OT - Oligodendrocyte OT - Pluripotent stem cells OT - Remyelination EDAT- 2014/07/30 06:00 MHDA- 2016/01/07 06:00 PMCR- 2015/09/01 CRDT- 2014/07/30 06:00 PHST- 2014/07/30 06:00 [entrez] PHST- 2014/07/30 06:00 [pubmed] PHST- 2016/01/07 06:00 [medline] PHST- 2015/09/01 00:00 [pmc-release] AID - sctm.2014-0041 [pii] AID - 20140041 [pii] AID - 10.5966/sctm.2014-0041 [doi] PST - ppublish SO - Stem Cells Transl Med. 2014 Sep;3(9):1100-9. doi: 10.5966/sctm.2014-0041. Epub 2014 Jul 28.