Human amniotic epithelial cell transplantation promotes neurogenesis and ameliorates social deficits in BTBR mice
Abstract Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interactions and communication and stereotypical patterns of behaviors, interests, or activities. Even with the increased prevalence of ASD, there is no defined standard drug tr...
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| Format: | Article |
| Language: | English |
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BMC
2019-05-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | http://link.springer.com/article/10.1186/s13287-019-1267-0 |
| _version_ | 1819178507865948160 |
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| author | Ruiyu Zhang Yulong Cai Rui Xiao Hongyu Zhong Xin Li Lihe Guo Haiwei Xu Xiaotang Fan |
| author_facet | Ruiyu Zhang Yulong Cai Rui Xiao Hongyu Zhong Xin Li Lihe Guo Haiwei Xu Xiaotang Fan |
| author_sort | Ruiyu Zhang |
| collection | DOAJ |
| description | Abstract Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interactions and communication and stereotypical patterns of behaviors, interests, or activities. Even with the increased prevalence of ASD, there is no defined standard drug treatment for ASD patients. Currently, stem cells, including human amniotic epithelial cell (hAEC) transplantation, seem to be a promising treatment for ASD, but the effectiveness needs to be verified, and the mechanism has not been clarified. Methods We intraventricularly transplanted hAECs into a 2-month-old BTBR T+tf/J (BTBR) mouse model of ASD. Behavior tests were detected 1 month later; hippocampal neurogenesis, neuroprogenitor cell (NPC) pool, and microglia activation were analyzed with immunohistochemistry and immunofluorescence; the levels of pro-inflammatory cytokines, brain-derived neurotrophic factor (BDNF), and TrkB in the hippocampus were determined by real-time PCR or western blotting. Results After intraventricular injection of hAECs into adult males, social deficits in BTBR mice were significantly ameliorated. In addition, hAEC transplantation restored the decline of neurogenesis and NPCs in the hippocampus of BTBR mice by expanding the stem cell pool, and the decreased levels of BDNF and TrkB were also rescued in the hippocampus of the hAEC-injected BTBR mice. Meanwhile, the transplantation of hAECs did not induce microglial overactivation or excessive production of pro-inflammatory cytokines in the hippocampus of BTBR mice. Conclusions Based on these results, we found that hAEC transplantation ameliorated social deficits and promoted hippocampal neurogenesis in BTBR mice. Our study indicates a promising therapeutic option that could be applied to ASD patients in the future. |
| first_indexed | 2024-12-22T21:43:39Z |
| format | Article |
| id | doaj.art-0c6ec5c63aa74ff8adab272afe9f81c6 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-22T21:43:39Z |
| publishDate | 2019-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-0c6ec5c63aa74ff8adab272afe9f81c62022-12-21T18:11:33ZengBMCStem Cell Research & Therapy1757-65122019-05-0110111310.1186/s13287-019-1267-0Human amniotic epithelial cell transplantation promotes neurogenesis and ameliorates social deficits in BTBR miceRuiyu Zhang0Yulong Cai1Rui Xiao2Hongyu Zhong3Xin Li4Lihe Guo5Haiwei Xu6Xiaotang Fan7Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University (Amy Medical University)Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University (Amy Medical University)Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University (Amy Medical University)Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University (Amy Medical University)Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University (Amy Medical University)Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of SciencesSouthwest Eye Hospital, Southwest Hospital, Third Military Medical University (Amy Medical University)Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University (Amy Medical University)Abstract Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interactions and communication and stereotypical patterns of behaviors, interests, or activities. Even with the increased prevalence of ASD, there is no defined standard drug treatment for ASD patients. Currently, stem cells, including human amniotic epithelial cell (hAEC) transplantation, seem to be a promising treatment for ASD, but the effectiveness needs to be verified, and the mechanism has not been clarified. Methods We intraventricularly transplanted hAECs into a 2-month-old BTBR T+tf/J (BTBR) mouse model of ASD. Behavior tests were detected 1 month later; hippocampal neurogenesis, neuroprogenitor cell (NPC) pool, and microglia activation were analyzed with immunohistochemistry and immunofluorescence; the levels of pro-inflammatory cytokines, brain-derived neurotrophic factor (BDNF), and TrkB in the hippocampus were determined by real-time PCR or western blotting. Results After intraventricular injection of hAECs into adult males, social deficits in BTBR mice were significantly ameliorated. In addition, hAEC transplantation restored the decline of neurogenesis and NPCs in the hippocampus of BTBR mice by expanding the stem cell pool, and the decreased levels of BDNF and TrkB were also rescued in the hippocampus of the hAEC-injected BTBR mice. Meanwhile, the transplantation of hAECs did not induce microglial overactivation or excessive production of pro-inflammatory cytokines in the hippocampus of BTBR mice. Conclusions Based on these results, we found that hAEC transplantation ameliorated social deficits and promoted hippocampal neurogenesis in BTBR mice. Our study indicates a promising therapeutic option that could be applied to ASD patients in the future.http://link.springer.com/article/10.1186/s13287-019-1267-0hAECsBTBRASDHippocampusNeurogenesis |
| spellingShingle | Ruiyu Zhang Yulong Cai Rui Xiao Hongyu Zhong Xin Li Lihe Guo Haiwei Xu Xiaotang Fan Human amniotic epithelial cell transplantation promotes neurogenesis and ameliorates social deficits in BTBR mice Stem Cell Research & Therapy hAECs BTBR ASD Hippocampus Neurogenesis |
| title | Human amniotic epithelial cell transplantation promotes neurogenesis and ameliorates social deficits in BTBR mice |
| title_full | Human amniotic epithelial cell transplantation promotes neurogenesis and ameliorates social deficits in BTBR mice |
| title_fullStr | Human amniotic epithelial cell transplantation promotes neurogenesis and ameliorates social deficits in BTBR mice |
| title_full_unstemmed | Human amniotic epithelial cell transplantation promotes neurogenesis and ameliorates social deficits in BTBR mice |
| title_short | Human amniotic epithelial cell transplantation promotes neurogenesis and ameliorates social deficits in BTBR mice |
| title_sort | human amniotic epithelial cell transplantation promotes neurogenesis and ameliorates social deficits in btbr mice |
| topic | hAECs BTBR ASD Hippocampus Neurogenesis |
| url | http://link.springer.com/article/10.1186/s13287-019-1267-0 |
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