Naho Fujiwara, Dorothy Lee, Bo Li, Agostino Pierro, Atsuyuki Yamataka
{"title":"胶质细胞源性神经营养因子在实验性赫氏胃肠病中增强肠道神经干细胞的神经发生。","authors":"Naho Fujiwara, Dorothy Lee, Bo Li, Agostino Pierro, Atsuyuki Yamataka","doi":"10.1007/s00383-024-05861-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Stem cell therapy offers a promising solution for congenital diseases like Hirschsprung's disease (HSCR). Optimizing stem cell efficacy by modifying the cells and their environment is crucial, but in vitro culture conditions need to be further improved. Glial cell-derived neurotrophic factor (GDNF) plays an important role in neuronal survival, proliferation, migration and differentiation during enteric nervous system (ENS) development. In this study, the effects of GDNF on neurites derived from an Ednrb knockout model were investigated with the aim of enhancing the neurogenic potential of enteric neural crest cells (ENCCs).</p><p><strong>Methods: </strong>Neurospheres were generated form Ednrb<sup>+/+</sup> (control) and Ednrb<sup>-/-</sup> mice at embryonic day13.5 (E13.5) with Sox10-green fluorescent protein (Venus) transgenic expression. These neurospheres were cultured in control media and neurospheres from Ednrb<sup>-/-</sup> were cultured with either control media or media supplemented with GDNF. ENCCs differentiation was assessed using immunofluorescence staining after 18 days.</p><p><strong>Results: </strong>GDNF-treated Ednrb<sup>-/-</sup> neurospheres showed increased size and higher density of Sox10-positive ENCCs compared to untreated Ednrb<sup>-/-</sup> neurospheres. GDNF also enhanced the distribution of both TUJ1-positive neurons and S100-positive glial cells.</p><p><strong>Conclusion: </strong>GDNF effectively enhanced the neurogenic potential of ENCCs from HSCR animal model. This finding is crucial for the development of cell therapy in HSCR.</p>","PeriodicalId":19832,"journal":{"name":"Pediatric Surgery International","volume":"40 1","pages":"274"},"PeriodicalIF":1.5000,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Enhancement of enteric neural stem cell neurogenesis by glial cell-derived neurotrophic factor in experimental Hirschsprung's disease.\",\"authors\":\"Naho Fujiwara, Dorothy Lee, Bo Li, Agostino Pierro, Atsuyuki Yamataka\",\"doi\":\"10.1007/s00383-024-05861-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Stem cell therapy offers a promising solution for congenital diseases like Hirschsprung's disease (HSCR). Optimizing stem cell efficacy by modifying the cells and their environment is crucial, but in vitro culture conditions need to be further improved. Glial cell-derived neurotrophic factor (GDNF) plays an important role in neuronal survival, proliferation, migration and differentiation during enteric nervous system (ENS) development. In this study, the effects of GDNF on neurites derived from an Ednrb knockout model were investigated with the aim of enhancing the neurogenic potential of enteric neural crest cells (ENCCs).</p><p><strong>Methods: </strong>Neurospheres were generated form Ednrb<sup>+/+</sup> (control) and Ednrb<sup>-/-</sup> mice at embryonic day13.5 (E13.5) with Sox10-green fluorescent protein (Venus) transgenic expression. These neurospheres were cultured in control media and neurospheres from Ednrb<sup>-/-</sup> were cultured with either control media or media supplemented with GDNF. ENCCs differentiation was assessed using immunofluorescence staining after 18 days.</p><p><strong>Results: </strong>GDNF-treated Ednrb<sup>-/-</sup> neurospheres showed increased size and higher density of Sox10-positive ENCCs compared to untreated Ednrb<sup>-/-</sup> neurospheres. GDNF also enhanced the distribution of both TUJ1-positive neurons and S100-positive glial cells.</p><p><strong>Conclusion: </strong>GDNF effectively enhanced the neurogenic potential of ENCCs from HSCR animal model. This finding is crucial for the development of cell therapy in HSCR.</p>\",\"PeriodicalId\":19832,\"journal\":{\"name\":\"Pediatric Surgery International\",\"volume\":\"40 1\",\"pages\":\"274\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2024-10-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pediatric Surgery International\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00383-024-05861-3\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PEDIATRICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric Surgery International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00383-024-05861-3","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PEDIATRICS","Score":null,"Total":0}
Enhancement of enteric neural stem cell neurogenesis by glial cell-derived neurotrophic factor in experimental Hirschsprung's disease.
Purpose: Stem cell therapy offers a promising solution for congenital diseases like Hirschsprung's disease (HSCR). Optimizing stem cell efficacy by modifying the cells and their environment is crucial, but in vitro culture conditions need to be further improved. Glial cell-derived neurotrophic factor (GDNF) plays an important role in neuronal survival, proliferation, migration and differentiation during enteric nervous system (ENS) development. In this study, the effects of GDNF on neurites derived from an Ednrb knockout model were investigated with the aim of enhancing the neurogenic potential of enteric neural crest cells (ENCCs).
Methods: Neurospheres were generated form Ednrb+/+ (control) and Ednrb-/- mice at embryonic day13.5 (E13.5) with Sox10-green fluorescent protein (Venus) transgenic expression. These neurospheres were cultured in control media and neurospheres from Ednrb-/- were cultured with either control media or media supplemented with GDNF. ENCCs differentiation was assessed using immunofluorescence staining after 18 days.
Results: GDNF-treated Ednrb-/- neurospheres showed increased size and higher density of Sox10-positive ENCCs compared to untreated Ednrb-/- neurospheres. GDNF also enhanced the distribution of both TUJ1-positive neurons and S100-positive glial cells.
Conclusion: GDNF effectively enhanced the neurogenic potential of ENCCs from HSCR animal model. This finding is crucial for the development of cell therapy in HSCR.
期刊介绍:
Pediatric Surgery International is a journal devoted to the publication of new and important information from the entire spectrum of pediatric surgery. The major purpose of the journal is to promote postgraduate training and further education in the surgery of infants and children.
The contents will include articles in clinical and experimental surgery, as well as related fields. One section of each issue is devoted to a special topic, with invited contributions from recognized authorities. Other sections will include:
-Review articles-
Original articles-
Technical innovations-
Letters to the editor