Characterization and intraspinal grafting of EGF/bFGF-dependent neurospheres derived from embryonic rat spinal cord

Chow, S. Y.; Moul, J.; Tobias, Christopher A.; Himes, B. Timothy; Liu, Yi; Obrocka, Maria; Hodge, Liberty K.; Tessler, Alan; Fischer, Itzhak

doi:10.1016/s0006-8993(00)02443-4

Cited by 134 publications

(100 citation statements)

References 62 publications

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“…Accordingly, multiple neuronal subtypes have been identified in cultures of the embryonic spinal cord (Richards et al, 1995;Dutton et al, 1998;Kalyani et al, 1998;Chow et al, 2000). Here we examined the specificity of neuronal subtypes in cultures of adult progenitors at the molecular level.…”

Section: Inability Of Adult Progenitors To Generate Specific Neuronalmentioning

confidence: 99%

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Transcription Factor Expression and Notch-Dependent Regulation of Neural Progenitors in the Adult Rat Spinal Cord

Yamamoto¹,

Nagao²,

Sugimori³

et al. 2001

J. Neurosci.

232

199

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Recent studies have demonstrated that neural stem cells and other progenitors are present in the adult CNS. Details of their properties, however, remain poorly understood. Here we examined the properties and control mechanisms of neural progenitors in the adult rat spinal cord at the molecular level. Adult and embryonic progenitors commonly expressed various homeodomain-type (Pax6, Pax7, Nkx2.2, and Prox1) and basic helix-loop-helix (bHLH)-type (Ngn2, Mash1, NeuroD1, and Olig2) transcriptional regulatory factors in vitro. Unlike their embryonic counterparts, however, adult progenitors could not generate specific neurons that expressed markers appropriate for spinal motoneurons or interneurons, including Islet1, Lim1, Lim3, and HB9. Cells expressing the homeodomain factors Pax6, Pax7, and Nkx2.2 also emerged in vivo in response to injury and were distributed in unique patterns in the lesioned spinal cord. However, neither the expression of the neurogenic bHLH factors including Ngn2, Mash1, and NeuroD1 nor subsequent generation of new neurons could be detected in injured tissue. Our results suggest that signaling through the cellsurface receptor Notch is involved in this restriction. The expression of Notch1 in vivo was enhanced in response to injury. Furthermore, activation of Notch signaling in vitro inhibited differentiation of adult progenitors, whereas attenuation of Notch signals and forced expression of Ngn2 significantly enhanced neurogenesis. These results suggest that both the intrinsic properties of adult progenitors and local environmental signals, including Notch signaling, account for the limited regenerative potential of the adult spinal cord.

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Section: Inability Of Adult Progenitors To Generate Specific Neuronalmentioning

confidence: 99%

“…Furthermore, neural progenitors could not differentiate into neurons when transplanted back into the spinal cord (Chow et al, 2000;Shihabuddin et al, 2000). Thus, de novo neurogenesis appears to be tightly restricted by the environment in vivo.…”

Section: Notch Signaling and Restricted Neurogenesis In The Adult Spimentioning

confidence: 99%

Transcription Factor Expression and Notch-Dependent Regulation of Neural Progenitors in the Adult Rat Spinal Cord

Yamamoto¹,

Nagao²,

Sugimori³

et al. 2001

J. Neurosci.

232

199

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“…In addition, the transplanted cells may have the potential to modulate the microenvironment of the injured spinal cord to support cell/axon growth and/or prevent secondary injury cascades (i.e., inflammation) [16][17][18]. It has been shown that grafts derived from the fetal spinal cord (FSC) contain lineage-restricted precursors (e.g., cells with a predetermined fate of motoneurons, interneurons, and glia cells), as well as residual populations of stem cells [19][20][21]. Moreover, FSC tissue has a relatively intact scaffold (i.e., 3-dimensional structure) to support survival, differentiation, and attachment of transplanted cells [22].…”

Section: Introductionmentioning

confidence: 99%

The Therapeutic Effectiveness of Delayed Fetal Spinal Cord Tissue Transplantation on Respiratory Function Following Mid-Cervical Spinal Cord Injury

et al. 2017

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Respiratory impairment due to damage of the spinal respiratory motoneurons and interruption of the descending drives from brainstem premotor neurons to spinal respiratory motoneurons is the leading cause of morbidity and mortality following cervical spinal cord injury. The present study was designed to evaluate the therapeutic effectiveness of delayed transplantation of fetal spinal cord (FSC) tissue on respiratory function in rats with mid-cervical spinal cord injury. Embryonic day-14 rat FSC tissue was transplanted into a C4 spinal cord hemilesion cavity in adult male rats at 1 week postinjury. The histological results showed that FSC-derived grafts can survive, fill the lesion cavity, and differentiate into neurons and astrocytes at 8 weeks post-transplantation. Some FSC-derived graft neurons exhibited specific neurochemical markers of neurotransmitter (e.g., serotonin, noradrenalin, or acetylcholine). Moreover, a robust expression of glutamatergic and γ-aminobutyric acid-ergic fibers was observed within FSC-derived grafts. Retrograde tracing results indicated that there was a connection between FSC-derived grafts and host phrenic nucleus. Neurophysiological recording of the phrenic nerve demonstrated that phrenic burst amplitude ipsilateral to the lesion was significantly greater in injured animals that received FSC transplantation than in those that received buffer transplantation under high respiratory drives. These results suggest that delayed FSC transplantation may have the potential to repair the injured spinal cord and promote respiratory functional recovery after mid-cervical spinal cord injury.

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“…Disappointingly, although in vitro differentiation of embryonic stem cells (ESCs) can result in nearly pure neuronal cultures (Bibel et al, 2004), the adult CNS presents greater challenges to survival and fate specification. Most cells in transplants die or show glial-restricted differentiation (Fricker et al, 1999;Chow et al, 2000;Cao et al, 2001). However, NSCs transplanted into brain areas undergoing active neurogenesis can produce significant numbers of region-appropriate neurons (Flax et al, 1998;Fricker et al, 1999;Shihabuddin et al, 2000;Cao et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Myocyte Enhancer Factor 2C as a Neurogenic and Antiapoptotic Transcription Factor in Murine Embryonic Stem Cells

McKercher²,

Cui³

et al. 2008

Journal of Neuroscience

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Cell-based therapies require a reliable source of cells that can be easily grown, undergo directed differentiation, and remain viable after transplantation. Here, we generated stably transformed murine ES (embryonic stem) cells that express a constitutively active form of myocyte enhancer factor 2C (MEF2CA). MEF2C has been implicated as a calcium-dependent transcription factor that enhances survival and affects synapse formation of neurons as well as differentiation of cardiomyocytes. We now report that expression of MEF2CA, both in vitro and in vivo, under regulation of the nestin enhancer effectively produces "neuronal" progenitor cells that differentiate into a virtually pure population of neurons. Histological, electrophysiological, and behavioral analyses demonstrate that MEF2C-directed neuronal progenitor cells transplanted into a mouse model of cerebral ischemia can successfully differentiate into functioning neurons and ameliorate stroke-induced behavioral deficits.

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Characterization and intraspinal grafting of EGF/bFGF-dependent neurospheres derived from embryonic rat spinal cord

Cited by 134 publications

References 62 publications

Transcription Factor Expression and Notch-Dependent Regulation of Neural Progenitors in the Adult Rat Spinal Cord

Transcription Factor Expression and Notch-Dependent Regulation of Neural Progenitors in the Adult Rat Spinal Cord

The Therapeutic Effectiveness of Delayed Fetal Spinal Cord Tissue Transplantation on Respiratory Function Following Mid-Cervical Spinal Cord Injury

Myocyte Enhancer Factor 2C as a Neurogenic and Antiapoptotic Transcription Factor in Murine Embryonic Stem Cells

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