Human neural progenitor cells derived from embryonic stem cells in feeder-free cultures

Dhara, Sujoy K.; Hasneen, Kowser; Machacek, David W.; Boyd, Nolan L.; Rao, Raj R.; Stice, Steven L.

doi:10.1111/j.1432-0436.2007.00256.x

Cited by 83 publications

(76 citation statements)

References 53 publications

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“…Recent studies have generated efficient tion compared to individual hESC-NP grafting 5 weeks after transplantation. Therefore, neuronal differentiation NPs from hESCs that have self-renewal potential from rosette-forming cells isolated during early hESC differof hESC-NPs after cotransplantation into the lesioned spinal cord has been improved when compared with NP entiation stages (20,24,34,37,45,76).…”

Section: The Effect and Fate Of Hesc-nps And Rat Scs In The Coculturementioning

confidence: 99%

“…The most commonly used cell types include, but are not limited ate all types of neural cells (27,49). These cells are derived from in vivo fetal/adult tissues (65) or pluripoto, olfactory ensheathing cells (OECs) (43,72,75), bone marrow and cord blood stromal cells (16,63,66), tent stem cells such as human embryonic stem cells (hESCs) in vitro (20,24,34,37,45,76). hESCs provide a Schwann cells (SCs) (7,9,21), and genetically modified 828 NIAPOUR ET AL.…”

Section: Introductionmentioning

confidence: 99%

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Cotransplantation of Human Embryonic Stem Cell-Derived Neural Progenitors and Schwann Cells in a Rat Spinal Cord Contusion Injury Model Elicits a Distinct Neurogenesis and Functional Recovery

et al. 2012

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Cotransplantation of neural progenitors (NPs) with Schwann cells (SCs) might be a way to overcome low rate of neuronal differentiation of NPs following transplantation in spinal cord injury (SCI) and the improvement of locomotor recovery. In this study, we initially generated NPs from human embryonic stem cells (hESCs) and investigated their potential for neuronal differentiation and functional recovery when cocultured with SCs in vitro and cotransplanted in a rat acute model of contused SCI. Cocultivation results revealed that the presence of SCs provided a consistent status for hESC-NPs and recharged their neural differentiation toward a predominantly neuronal fate. Following transplantation, a significant functional recovery was observed in all engrafted groups (NPs, SCs, NPs + SCs) relative to the vehicle and control groups. We also observed that animals receiving cotransplants established a better state as assessed with the BBB functional test. Immunohistofluorescence evaluation 5 weeks after transplantation showed invigorated neuronal differentiation and limited proliferation in the cotransplanted group when compared to the individual hESC-NPgrafted group. These findings have demonstrated that the cotransplantation of SCs with hESC-NPs could offer a synergistic effect, promoting neuronal differentiation and functional recovery.

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Section: The Effect and Fate Of Hesc-nps And Rat Scs In The Coculturementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cotransplantation of Human Embryonic Stem Cell-Derived Neural Progenitors and Schwann Cells in a Rat Spinal Cord Contusion Injury Model Elicits a Distinct Neurogenesis and Functional Recovery

et al. 2012

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“…Fixed cells were stained as described previously [3] and data were acquired using FACSCalibur system (BD Biosciences). Analysis was done with FlowJo analysis software (Tree Star, Inc., Ashland, OR, http://www.flowjo.com/).…”

Section: Flow Cytometrymentioning

confidence: 99%

“…We have previously derived a self-renewing but fate-restricted neural progenitor (NP) cell line from hESC that can generate highly enriched neuronal populations under specific conditions [2,3], thus serving as a potentially unlimited source of human neurons for both basic [4] and applied research [5]. This progenitor line has previously been used to study neurotoxicity, differentiation to specific neuronal phenotypes, drug screening, and transplantation experiments in rodent models of stroke [4,5].…”

Section: Introductionmentioning

confidence: 99%

Neurotrophic Effects of Leukemia Inhibitory Factor on Neural Cells Derived from Human Embryonic Stem Cells

et al. 2012

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Various growth factor cocktails have been used to proliferate and then differentiate human neural progenitor (NP) cells derived from embryonic stem cells (ESC) for in vitro and in vivo studies. However, the cytokine leukemia inhibitory factor (LIF) has been largely overlooked. Here, we demonstrate that LIF significantly enhanced in vitro survival and promoted differentiation of human ESC-derived NP cells. In NP cells, as well as NP-derived neurons, LIF reduced caspase-mediated apoptosis and reduced both spontaneous and H 2 O 2 -induced reactive oxygen species in culture. In vitro, NP cell proliferation and the yield of differentiated neurons were significantly higher in the presence of LIF. In NP cells, LIF enhanced cMyc phosphorylation, commonly associated with self-renewal/proliferation. Also, in differentiating NP cells LIF activated the phosphoinositide 3-kinase and signal transducer and activator of transcription 3 pathways, associated with cell survival and reduced apoptosis. When differentiated in LIF 1 media, neurite outgrowth and ERK1/2 phosphorylation were potentiated together with increased expression of gp130, a component of the LIF receptor complex. NP cells, pretreated in vitro with LIF, were effective in reducing infarct volume in a model of focal ischemic stroke but LIF did not lead to significantly improved initial NP cell survival over nontreated NP cells. Our results show that LIF signaling significantly promotes human NP cell proliferation, survival, and differentiation in vitro. Activated LIF signaling should be considered in cell culture expansion systems for future human NP cell-based therapeutic transplant studies.

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“…Media with N2 produced higher number of hNPs without proliferation, media with non-essential amino acids and knock-out serum replacement produced few er number of hNPs with p roliferation, a nd by five passages the cul ture consisted of >97% hNPs. This resulted in an efficient, robust, repeatable differentiation system suitable for generating large populations of hNP cells from hESCs (Dhara et al, 2008).…”

Section: Npcs and Neurons Differentiation Potential Of Embryonic Stemmentioning

confidence: 99%

Embryonic Stem Cell in the Therapy of Neurodegenerative Diseases

Fan¹,

Tang²,

Wang³

et al. 2011

Embryonic Stem Cells - Recent Advances in Pluripotent Stem Cell-Based Regenerative Medicine

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Human neural progenitor cells derived from embryonic stem cells in feeder-free cultures

Cited by 83 publications

References 53 publications

Cotransplantation of Human Embryonic Stem Cell-Derived Neural Progenitors and Schwann Cells in a Rat Spinal Cord Contusion Injury Model Elicits a Distinct Neurogenesis and Functional Recovery

Cotransplantation of Human Embryonic Stem Cell-Derived Neural Progenitors and Schwann Cells in a Rat Spinal Cord Contusion Injury Model Elicits a Distinct Neurogenesis and Functional Recovery

Neurotrophic Effects of Leukemia Inhibitory Factor on Neural Cells Derived from Human Embryonic Stem Cells

Embryonic Stem Cell in the Therapy of Neurodegenerative Diseases

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