Differentiation of neural lineage cells from human pluripotent stem cells

Schwartz, Philip H.; Brick, David J.; Stover, Alexander E.; Loring, Jeanne F.; Müller, Franz‐Josef

doi:10.1016/j.ymeth.2008.03.007

Cited by 73 publications

(44 citation statements)

References 126 publications

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“…The same effect is observed for the EBs generated using the 4-/4+ protocol, suggesting that the effects on differentiation take longer in the miPSC-derived EBs. While iPSCs and ESCs use the same signalling pathways when differentiating into neural phenotypes, high variability in differentiation efficiency is observed between different cell lines, regardless of whether they are iPSCs or ESCs [7,12,49]. Thus, it may be possible to attribute the differences between the miPSC-and mESC-derived EBs to differences between the specific cell lines rather than as representing general differences between iPSCs and ESCs.…”

Section: 23mentioning

confidence: 99%

Engineering personalized neural tissue by combining induced pluripotent stem cells with fibrin scaffolds

et al. 2015

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Induced pluripotent stem cells (iPSCs) are generated from adult somatic cells through the induction of key transcription factors that restore the ability to become any cell type found in the body. These cells are of interest for tissue engineering due to their potential for developing patient-specific therapies. As the technology for generating iPSCs advances, it is important to concurrently investigate protocols for the efficient differentiation of these cells to desired downstream phenotypes in combination with biomaterial scaffolds as a way of engineering neural tissue. For such applications, the generation of neurons within three dimensional fibrin scaffolds has been well characterized as a cell-delivery platform for murine embryonic stem cells (ESCs) but has not yet been applied to murine iPSCs. Given that iPSCs have been reported to differentiate less effectively than ESCs, a key objective of this investigation is to maximize the proportion of iPSC-derived neurons in fibrin through the choice of differentiation protocol. To this end, this study compares two EB-mediated protocols for generating neurons from murine iPSCs and ESCs: an 8-day 4-/4+ protocol using soluble retinoic acid in the last 4 days and a 6-day 2-/4+ protocol using soluble retinoic acid and the small molecule sonic hedgehog agonist purmorphamine in the last 4 days. EBs were then seeded in fibrin scaffolds for 14 days to allow further differentiation into neurons. EBs generated by the 2-/4+ protocol yielded a higher percentage of neurons compared to those from the 4-/4+ protocol for both iPSCs and ESCs. The results demonstrate the successful translation of the fibrin-based cell-delivery platform for use with murine iPSCs and furthermore that the proportion of neurons generated from murine iPSC-derived EBs seeded in fibrin can be maximized using the 2-/4+ differentiation protocol. Together, these findings validate the further exploration of 3D fibrin-based scaffolds as a method of delivering neuronal cells derived from iPSCs -an important step toward the development of iPSC-based tissue engineering strategies for spinal cord injury repair.

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Section: 23mentioning

confidence: 99%

Engineering personalized neural tissue by combining induced pluripotent stem cells with fibrin scaffolds

et al. 2015

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“…Since then, MSCs have been isolated from many other adult tissues such a umbilical cord blood, placenta, amniotic fluid, peripheral blood, adipose tissue and various other somatic tissues sharing the regenerative as well as the immunomodulatory properties of MSCs (In 't Anker, Scherjon et al 2004;Zuk 2010;Bianco 2011) but have mainly been characterized after isolation from bone marrow. MSCs can be expanded in vitro as plastic adherent cells with a fibroblast-like morphology and can be differentiated into cells of mesodermal lineage (osteocytes, chondrocytes and adipocytes) (Pittenger, Mackay et al 1999) as well as cells from other embryonic lineages (Sanchez-Ramos 2006;Schwartz, Brick et al 2008). At present, MSCs lack a definitive marker and no single marker has been identified distinguishing MSCs however the International Society for Stem Cell Research has outlined minimal criteria to characterize human MSCs, these cells have been reported to be positive for CD73, CD90, CD105 and major histocompatibility complex class I (HLA-ABC).…”

Section: The Biology and Originality Of Mesenchymal Stem Cells And Thmentioning

confidence: 99%

Mesenchymal Stem Cells as Immunomodulators in Transplantation

Zghoul¹,

Aljurf²,

Dermime³

2012

New Advances in Stem Cell Transplantation

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“…In a review article on neural cell differentiation methods Schwartz et al (2008) showed many variations in the use of the materials to induce the differentiation of mesenchymal cells into neural cells. FGF and EGF have important role in the maintenance and expansion of differentiated cells (Schwartz et al 2008).…”

Section: Introductionmentioning

confidence: 99%

“…FGF and EGF have important role in the maintenance and expansion of differentiated cells (Schwartz et al 2008). What is important is none of the methods was used to induce the hUCMs differentiation into neural cells.…”

Section: Introductionmentioning

confidence: 99%

Neural differentiation of human umbilical cord matrix-derived mesenchymal cells under special culture conditions

et al. 2014

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Many neural disorders are characterized by the loss of one or several types of neural cells. Human umbilical cord-derived mesenchymal cells (hUCMs) are capable of differentiating into neuron, astroglia-like and oligodendrocyte cell types. However, a reliable means of inducing the selective differentiation of hUCMs into neural cells in vitro has not yet been established. For induction of neural differentiation, hUCMs were seeded onto sterile glass slides and six various cocktails using a base medium (DMEM/LG) supplemented with 10 % FBS, retinoic acid (RA), dimethyl sulfoxide (DMSO), epidermal growth factor (EGF) and fibroblast growth factor (FGF) were used to compare their effect on neuronal, astrocyte and oligodandrocyte differentiation. The hUCMs were positive for mesenchymal markers, while they were negative for hematopoietic markers. Differentiation to adipogenic and osteogenic lineage was detected in these cells. Our data revealed that the cocktail consisting of DMEM/LG, FBS, RA, FGF, and EGF (DF/R/Fg/E group) induced hUCM cells to express the highest percentage of nestin, ß-tubulin III, neurofilament, and CNPase. The DF/Ds/Fg/E group led to the highest percentage of GFAP expression. While the expression levels of NF, GFAP, and CNPase were the lowest in the DF group. The least percentage of nestin and ß-tubulin III expression was observed in the DF/Ds group. We may conclude that FGF and EGF are important inducers for differentiation of hUCMs into neuron, astrocyte and oligodendrocyte. RA can induce hUCMs to differentiate into neuron and oligodendrocyte while for astrocyte differentiation DMSO had a pivotal role.

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Differentiation of neural lineage cells from human pluripotent stem cells

Cited by 73 publications

References 126 publications

Engineering personalized neural tissue by combining induced pluripotent stem cells with fibrin scaffolds

Engineering personalized neural tissue by combining induced pluripotent stem cells with fibrin scaffolds

Mesenchymal Stem Cells as Immunomodulators in Transplantation

Neural differentiation of human umbilical cord matrix-derived mesenchymal cells under special culture conditions

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