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Copyright ©2014 Baishideng Publishing Group Co.
World J Stem Cells. Jan 26, 2014; 6(1): 11-23
Published online Jan 26, 2014. doi: 10.4252/wjsc.v6.i1.11
Table 1 Protocols and in vivo studies for oligodendrocyte progenitor cells differentiation from human pluripotent stem cells
Growth factorsCell sourceCell characteristicsRef.
EGF-dependent protocol
RA/EGF (short FGF-2 exposure)hESC lines: H1 and H7Olig1 (80%-90%), Sox10 (76%-84%), NG2 (95%); remyelinated in a rat thoracic contusion modelNistor et al[21], 2005; Keirstead et al[19], 2006; Li et al[13], 2013
RA/EGF (short FGF-2 exposure)hiPSC lines: Royan hiPSC1, hiPSC8> 90% Olig2, Sox 10, > 80% NG2 and PDGFRα; tested in a rat model of optic chiasm demyelinationPouya et al[33], 2011
RA/EGF (short FGF-2 exposure)hESC H7 lineOPCs remyelinated in a rat cervical contusion modelSharp et al[94], 2010
RA/EGF (short FGF-2 exposure)hiPSC lines: 201B7, 253G1O4+ cells were observed in EGF-dependent protocolOgawa et al[20], 2011
PDGF-dependent protocol
PDGF/FGF-2 (short EGF exposure)SNUhES1 linePDGFRα (81%), A2B5 (90.4%), NG2 (91.3%) and O1 (81%); myelinate axons in co-cultures with fetus hippocampal neurons.Kang et al[24], 2007
RA/Shh/FGF-2/PDGFhESC lines: H1, H9 H14> 80% PDGFRα+, also co-express Olig2, Nkx2.2, Sox10 and NG2Hu et al[26], 2009
RA/Shh/FGF-2/PDGFhiPSC lines: K04, C14, and C2770%-90% Olig2+/Nkx2.2+, OPCs myelinated the brains of myelin-deficient shiverer miceWang et al[7], 2013
FGF-2/EGF/PDGF/CNTF plus laminin; Shh, PDGF, IGF-1, EGF, FGF-2 and CNTF plus RA and lamininhESC lines: HS360 and HS362; Regea 06/040 and Regea 08/023> 90% NG2+, > 80% PDGFRα+; multilayered myelin sheet formation around axons was detected in co-culture with neuronal cellsSundberg et al[28], 2010 Sundberg et al[27], 2011
Noggin/FGF-2/FGF-4/PDGF/EGFhESC H1 line> 95% cells expressing Sox10, A2B5, PDGFRα, NG2, O4, O1; increased neurological response in a rat contusion modelKerr et al[29], 2010
Table 2 Effects of extracellular matrices proteins on neural differentiation of pluripotent stem cells
ECM proteinIntegrinsCell sourceNeural differentiationRef.
Laminin Matrigel (rich in laminin)α6β1 α3β1HESC lines: TE03 and TE06Neuronal generation and neurite outgrowth were significantly greater on laminin and laminin-rich Matrigel than fibronectin, poly-D-lysine, and collagen IMa et al[16], 2008
Fibronectinα5β1Oligodendrocyte progenitor cells from ratsPromoted OPC survival, proliferation, migration, process extension, and OPC purityHu et al[35], 2009
Vitronectinαvβ1, αvβ3, αvβ5hESC lines: Miz-hES4, Miz-hES6Promoted oligodendrocyte differentiation in the presence of RA/Shh/NogginGil et al[36], 2009
Collagen IVα1β1, α10β1Rabbit neural progenitor cellsConducive for both neuronal and glial cell differentiationRaghavan et al[61], 2013
Collagen Iα2β1Rabbit neural progenitor cellsConducive for both neuronal and glial cell differentiationRaghavan et al[61], 2013
Vitronectin-derived synthetic peptide acrylate surfaceαvβ5hESC line: H1Promoted oligodendrocyte progenitor differentiation; higher NG2 expression compared to MatrigelLi et al[13], 2013
Heparan sulfateBinding heparinRabbit neural progenitor cellsAddition of heparan sulfate to collagen mixtures improved neuronal differentiationRaghavan et al[61], 2013
Table 3 Protocols and in vivo studies for neural progenitor cells differentiation from human pluripotent stem cells
Growth factorsCell sourceCell characteristicsRef.
EB-based protocol
FGF-2/RA/ascorbic acid, db-cAMP, HAg16 hiPSC lines13 of the cell lines produced functional motor neurons. Treat with BDNF, GDNF, CNTF to produce motor neurons (4%-15% ISL+ neurons)Boulting et al[43], 2011
RA/FGF-2hESC lines: H7, hCSC14, hCSC14-CL1Produce neuronal progenitors (> 95% nestin and Musashi-1), can become cholinergic neurons, GABA neurons, etcNistor et al[47], 2011
Isolated Rosette expanded with EGF/FGF-2hiPSC linesGenerate long-term expandable neuro-epithelial like stem cells (Lt-NES); in stoke model, the cells improved recovery of fine forelimb movementsOki et al[53], 2012
RA/ShhhESC lines H1 and H9To generate motor neurons (50% HB9+ motor neurons)Hu et al[51], 2009
Monolayer-based protocol
Noggin and SB431542hESC line: H9 hiPSC lines: iPS-14, iPS-27> 80% PAX6+ cells; Shh/FGF8 for midbrain dopamine neurons; BDNF, Shh, RA, ascorbic acid for motor neuronsChambers et al[12], 2009
Noggin and SB431542hESC line: H9 hiPSC line: 253G4Treat BDNF, GDNF, NT-3 for forebrain neurons which secrete Aβ for drug screening.Yahata et al[52], 2011
Noggin only; FGF-2 may be added at later stagehESC line: H1, H7, H9> 90% nestin, musashi, and PSA-NCAM; For TH neurons, add Shh/FGF8/ascorbic acid; followed by BDNF, GDNF, ascorbic acid and lamininGerrard et al[48], 2005
FGF-2hESC line: SA002 and AS034> 90% nestin, NCAM; For neuronal lineage, add Shh/FGF8; after differentiation TH+ cells, MAPab+ cells and astrocytes existedAxell et al[49], 2009
Table 4 Three-dimensional natural and synthetic extracellular matrices scaffolds for neural differentiation of pluripotent stem cells
ScaffoldsCell sourceNeural differentiationRef.
Poly(lactic-co-glycolic acid) and poly(L- lactic acid) scaffoldshESCEnhanced numbers of neural structures and staining of nestin and β-tubulin III were observedLevenberg et al[74], 2005
Synthetic hydrogel matrix PuraMatrixhESC-derived neuronal cellsHESC-derived neurons, astrocytes, and oligodendrocytes grew, matured and migrated in hydrogel; neuronal cells had electrically active connections.Ylä-Outinen et al[76], 2012
Poly(epsilon-caprolactone)-poly(beta-hydroxybutyrate) scaffoldsMouse iPSCsImproved iPSCs to differentiate into neurons and inhibited other differentiations.Kuo et al[79], 2012
Polycaprolactone nanofiber matricesHESC-derived neural precursorsAligned fibrous matrices showed higher rate of neuronal differentiation compared to random micro- and nano- fibers (62%-86% vs 27%-32%).Mahairaki et al[77], 2011
Polyurethane nanofibrous scaffoldshESC line SA002Neuronal differentiation was preferred over astrocyte differentiation.Carlberg et al[80], 2009
Tissue-engineered fibrin scaffoldsMouse ESC-derived NPCsEnhanced NPC survival and directed differentiation into neurons.Johnson et al[82], 2010
PET microfibrous scaffoldsMouse ESC D3 lineEnhanced neuronal differentiation indicated by nestin, Nurr1, and tyrosine hydroxylase compared to 2-D culture.Liu et al[84,85], 2013, 2013
Multiwalled carbon nanotube modified PET microfibrous scaffoldsMouse ESC D3 lineEnhanced neuronal differentiation compared to unmodified scaffoldsZang et al[83], 2013
Chitin-alginate 3-D microfibrous scaffoldshESC line: HUES 7 hiPSC lines: PD-iPS5 and hFib2-iPS4Efficient neuronal differentiation: > 95% nestin+; able to mature into neurons (> 90% β-tubulin III+)Lu et al[75], 2012
3-D ECM scaffolds derived from ESC aggregatesMouse ESC D3 lineECM scaffolds derived from RA-treated EBs enhanced nestin and β-tubulin III expressionsSart et al[60], 2013
Inverted colloidal crystal (ICC) scaffolds containing alginate, poly(gamma- glutamic acid), and surface peptide; or chitin-chitosan-gelatin ICC scaffoldsMouse iPSCsAccelerated neuronal differentiation (β-tubulin III expression) of iPSCs.Kuo et al[86,87], 2013, 2013