Low concentrations of extracellular FGF-2 are sufficient but not essential for neurogenesis from human neural progenitor cells

Nelson, Aaron D.; Svendsen, Clive N.

doi:10.1016/j.mcn.2006.06.003

Cited by 30 publications

(37 citation statements)

References 41 publications

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“…Our results could differ from this report because of the cell type and total number transplanted. Furthermore, hNPC require one round of final cell division to produce neurons within a neurogenic environment (20,21). We hypothesize that the intact or lesioned brain environment does not provide those signals which results in a block on division and differentiation into neurons.…”

Section: Discussionmentioning

confidence: 96%

Lesion-Induced Increase in Survival and Migration of Human Neural Progenitor Cells Releasing GDNF

et al. 2008

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The use of human neural progenitor cells (hNPC) has been proposed to provide neuronal replacement or astrocytes delivering growth factors for brain disorders such as Parkinson's and Huntington's disease. Success in such studies likely requires migration from the site of transplantation and integration into host tissue in the face of ongoing damage. In the current study, hNPC modified to release glial cell line derived neurotrophic factor (hNPC GDNF ) were transplanted into either intact or lesioned animals. GDNF release itself had no effect on the survival, migration or differentiation of the cells. The most robust migration and survival was found using a direct lesion of striatum (Huntington's model) with indirect lesions of the dopamine system (Parkinson's model) or intact animals showing successively less migration and survival. No lesion affected differentiation patterns. We conclude that the type of brain injury dictates migration and integration of hNPC which has important consequences when considering transplantation of these cells as a therapy for neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 96%

Lesion-Induced Increase in Survival and Migration of Human Neural Progenitor Cells Releasing GDNF

et al. 2008

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“…Although it has been difficult to find immunocytochemical markers that specifically identify these cells under the microscope, our Western analysis suggested that at least three markers of radial glia (BLBP, Vimentin, and S100) are increased in high EGF. When removed from the mitogen EGF, these radial gliallike cells undergo further division that produces neurons in this culture system [23,24], thus leading to a higher proportion of neurons. Therefore, high EGF concentrations both increase the rate of division, allowing large numbers of cells to be generated, and enhance neuronal output from these cultures.…”

Section: Discussionmentioning

confidence: 99%

“…Previous results suggest that low concentrations of FGF-2 can influence hNPC to undergo increased neurogenesis, whereas high concentrations of FGF-2 are inhibitory to neurogenesis [24]. It was therefore possible that FGF-2 released from the differentiating progenitors contributed to the increased neurogenesis.…”

Section: Growth Of Neurospheres In High Egf Leads To Increased Neurogmentioning

confidence: 94%

“…By growing cells in a higher concentration of EGF, it seemed reasonable to hypothesize that more cells within the core of the neurosphere would be stimulated to divide as nestin/GFAP-positive progenitors and not divide to form neuroblasts [23,24]. To investigate this possibility, hNPC were cultured in the medium with 20 or 100 ng/ml EGF for 14 days.…”

Section: Increased Elongated Cell Types Present In High-egf Hnpc Cultmentioning

confidence: 99%

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A High Concentration of Epidermal Growth Factor Increases the Growth and Survival of Neurogenic Radial Glial Cells Within Human Neurosphere Cultures

2007

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Human neural progenitor cells (hNPC) isolated from the fetal cortex can be expanded as aggregates of cells termed neurospheres. Traditional methods have used 20 ng/ml epidermal growth factor (EGF) to drive the proliferation of these cells. Here, we show that 100 ng/ml EGF can significantly increase growth rates of hNPC at later passages. This was through increased survival of dividing cells rather than increased proliferation and associated with prolonged activation of ErbB2 and phosphorylated Akt. High EGF also resulted in a larger proportion of elongated "radial glial"-like cells within the growing neurospheres and increased expression of the radial glial markers. The number of new neurons generated from cultures maintained in 100 ng/ml EGF was significantly higher than from 20 ng/ml EGF. Thus, high concentrations of EGF increase the survival of a highly neurogenic human radial glial cell. STEM CELLS 2008;26:348 -355 Disclosure of potential conflicts of interest is found at the end of this article.

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“…9 However, the exact roles of various growth factors in neural differentiation remain to be elucidated to improve the efficiency of cell differentiation. Among the studies on neural differentiation, basic fibroblast growth factor (bFGF) is known to be an important growth factor that increases neurite extensions in PC12 cells, 10 increases neurogenesis from human NPCs, 11 and stimulates neural cell differentiation. 4 bFGF is also used to maintain the undifferentiated human ESCs.…”

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confidence: 99%

In VitroRegulation of Neural Differentiation and Axon Growth by Growth Factors and Bioactive Nanofibers

Lam

Patel

Wang

et al. 2010

Tissue Engineering Part A

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Human embryonic stem cell (ESC)-derived neural cells are a potential cell source for neural tissue regeneration. Understanding the biochemical and biophysical regulation of neural differentiation and axon growth will help us develop cell therapies and bioactive scaffolds. We demonstrated that basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) had different effects on human ESC differentiation into neural cells. EGF was more effective in inducing expression of neuron and glial markers and cell extensions. In addition to biochemical cues, poly(l-lactic acid) scaffolds with aligned nanofibers increased axon growth from ESC-derived neural cells, demonstrating the significant effects of biophysical guidance at nanoscale. To combine the biochemical and biophysical cues, bFGF and EGF were either adsorbed or bound to heparin on nanofibrous scaffolds. EGF, but not bFGF, was effectively adsorbed onto nanofibers. However, adsorbed EGF and bFGF did not effectively enhance axon growth. In contrast, immobilization of bFGF or EGF onto nanofibers using heparin as the adapter molecule significantly promoted axon growth. This study elucidated the effect of bFGF and EGF in neural differentiation and axon growth, and demonstrated a method to immobilize active bFGF and EGF onto aligned nanofibers to promote neural tissue regeneration.

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Low concentrations of extracellular FGF-2 are sufficient but not essential for neurogenesis from human neural progenitor cells

Cited by 30 publications

References 41 publications

Lesion-Induced Increase in Survival and Migration of Human Neural Progenitor Cells Releasing GDNF

Lesion-Induced Increase in Survival and Migration of Human Neural Progenitor Cells Releasing GDNF

A High Concentration of Epidermal Growth Factor Increases the Growth and Survival of Neurogenic Radial Glial Cells Within Human Neurosphere Cultures

In VitroRegulation of Neural Differentiation and Axon Growth by Growth Factors and Bioactive Nanofibers

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