Growth Factor Changes in Cerebrospinal Fluid of Children with Mental Retardation before and after Neural Precursor Cell Transplantation

Objective: To investigate growth factor changes in cerebrospinal fluid (CSF) of children with mental retardation (MR) before and after neural precursor cell transplantation (NPCT), in an attempt to provide experimental support for the clinical treatment of MR with NPCT. Methods: The study comprised of 28 MR children who received twice NPCT in our hospital. CSF was collected at both times of NPCT to assess growth factors by ELISA. In addition, the content of insulinlike growth factor 1 (IGF-1) in CSF was assayed to determine possible correlations between IGF-1 changes and the short-term therapeutic effect of NPCT. Results: Of all the growth factors detected in CSF, only IGF-1 was increased significantly after NPCT (P<0.05). Fifteen of the twenty-eight MR children achieved short-term therapeutic efficacy, whereby the content of IGF-1 after NPCT was significantly higher than that before NPCT (P<0.05). There was no difference in IGF-1 content before and after NPCT in the remaining 13 MR children without shortterm therapeutic effect (P=0.657). There was a significant difference in IGF-change between the two groups of patients (P<0.05). Conclusion: IGF-1 may be one of the mechanisms contributing to the therapeutic effect of NPCT.

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NEDD4-2 (neural precursor cell expressed, developmentally down-regulated 4-2) negatively regulates TGF-β (transforming growth factor-β) signalling by inducing ubiquitin-mediated degradation of Smad2 and TGF-β type I receptor

Biochemical Journal ◽

10.1042/bj20040738 ◽

2005 ◽

Vol 386 (3) ◽

pp. 461-470 ◽

Cited By ~ 142

Author(s):

Go KURATOMI ◽

Akiyoshi KOMURO ◽

Kouichiro GOTO ◽

Masahiko SHINOZAKI ◽

Keiji MIYAZAWA ◽

...

Keyword(s):

Growth Factor ◽

Transforming Growth Factor ◽

Ubiquitin Ligases ◽

Transforming Growth Factor Β ◽

Precursor Cell ◽

Neural Precursor ◽

Type I ◽

Dependent Manner ◽

E3 Ubiquitin Ligases ◽

Neural Precursor Cell

Inhibitory Smad, Smad7, is a potent inhibitor of TGF-β (transforming growth factor-β) superfamily signalling. By binding to activated type I receptors, it prevents the activation of R-Smads (receptor-regulated Smads). To identify new components of the Smad pathway, we performed yeast two-hybrid screening using Smad7 as bait, and identified NEDD4-2 (neural precursor cell expressed, developmentally down-regulated 4-2) as a direct binding partner of Smad7. NEDD4-2 is structurally similar to Smurfs (Smad ubiquitin regulatory factors) 1 and 2, which were identified previously as E3 ubiquitin ligases for R-Smads and TGF-β superfamily receptors. NEDD4-2 functions like Smurfs 1 and 2 in that it associates with TGF-β type I receptor via Smad7, and induces its ubiquitin-dependent degradation. Moreover, NEDD4-2 bound to TGF-β-specific R-Smads, Smads 2 and 3, in a ligand-dependent manner, and induced degradation of Smad2, but not Smad3. However, in contrast with Smurf2, NEDD4-2 failed to induce ubiquitination of SnoN (Ski-related novel protein N), although NEDD4-2 bound to SnoN via Smad2 more strongly than Smurf2. We showed further that overexpressed NEDD4-2 prevents transcriptional activity induced by TGF-β and BMP, whereas silencing of the NEDD4-2 gene by siRNA (small interfering RNA) resulted in enhancement of the responsiveness to TGF-β superfamily cytokines. These data suggest that NEDD4-2 is a member of the Smurf-like C2-WW-HECT (WW is Trp-Trp and HECT is homologous to the E6-accessory protein) type E3 ubiquitin ligases, which negatively regulate TGF-β superfamily signalling through similar, but not identical, mechanisms to those used by Smurfs.

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Clinical Observation of Electroencephalographic Changes and Risk of Convulsion Occurrence in Children Receiving Neural Precursor Cell Transplantation

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527317666180424121947 ◽

2018 ◽

Vol 17 (3) ◽

pp. 233-239 ◽

Cited By ~ 1

Author(s):

Suqing Qu ◽

Weipeng Liu ◽

Hui Yang ◽

Zhaoyan Wang ◽

Yinxiang Yang ◽

...

Keyword(s):

Cell Transplantation ◽

Therapeutic Efficacy ◽

Precursor Cell ◽

Simultaneous Occurrence ◽

Neural Precursor ◽

Neural Precursor Cell ◽

Before And After ◽

Post Operation ◽

History Of ◽

Eeg Changes

Purpose: This study was intended to observe electroencephalographic (EEG) changes and convulsion attacks in children receiving neural precursor cell transplantation, and to explore the possibility of electrophysiological changes and risk of convulsion occurrence after cell transplantation. Method: 228 children were included in this study who received neural precursor cell transplantation in our hospital between March 2008 and July 2012. No history of convulsion attacks was elicited before cell transplantation. Data about EEG change and convulsion occurrence before and after cell transplantation were analyzed statistically. Results: Of the 228 pediatric patients, EEG improvement, deterioration and no significant change were observed in 60, 45 and 122 patients, respectively. One month after transplantation, four (1.76%) patients experienced new convulsions. Of the 227 patients, 25 showed increased and/or abnormal discharges on EEG. Of these, 19 underwent EEG re-examination six months post-operation. Except the convulsive cases mentioned above, there were no new cases of convulsions in the remaining patients. Of the 27 patients including those with abnormal discharge, increased discharge and convulsion attacks, 17 achieved varying degrees of therapeutic efficacy. Conclusion: Intraventricular transplantation of neural precursor cells is associated with EEG changes in some children and clinical convulsion attacks in individual patients. However, these abnormal changes do not last long and usually return to normal levels within 1-6 months after surgery, along with disappearance of convulsions. Simultaneous occurrence of EEG changes and convulsions do not appear to affect therapeutic efficacy.

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