Traduction: G.M.
Behav Brain Res. 2016 Oct 4. pii: S0166-4328(16)30762-8. doi: 10.1016/j.bbr.2016.10.004.
Human adipose-derived stem cells ameliorate repetitive behavior, social deficit and anxiety in a VPA-induced autism mouse model
Author information
- 1Department of Pharmacology, College of Medicine, Neuroscience Research Institute, Gachon University, Incheon 406-799, Republic of Korea; Department of Pharmacology, College of Medicine, Seoul National University, Seoul, Republic of Korea.
- 2Department of Pharmacology, College of Medicine, Neuroscience Research Institute, Gachon University, Incheon 406-799, Republic of Korea.
- 3Department of Pharmacology, College of Medicine, Seoul National University, Seoul, Republic of Korea.
- 4Stem Cell Research Center, K stem cell Co., Ltd., Seoul, Republic of Korea.
- 5Department of Pharmacology, College of Medicine, Neuroscience Research Institute, Gachon University, Incheon 406-799, Republic of Korea. Electronic address: yhsuh@gachon.ac.kr
- 6Department of Pharmacology, College of Medicine, Neuroscience Research Institute, Gachon University, Incheon 406-799, Republic of Korea. Electronic address: kachang74@gmail.com
Abstract
Le trouble
du spectre de l'autisme (TSA) est un trouble neurodéveloppemental
complexe caractérisé par des déficiences dans les interactions sociales
et la communication, et les "patients" présentent souvent des
comportements répétitifs. Bien
que la prévalence globale des TSA a augmenté au fil du temps,
l'étiologie et les traitements pour les TSA sont mal compris. Récemment, certains chercheurs ont suggéré que les cellules souches ont un potentiel thérapeutique pour les TSA. Ainsi,
dans la présente étude, nous avons étudié les effets thérapeutiques des
cellules souches dérivées de tissu adipeux humain (hASCs), une sorte de
cellules souches mésenchymateuses (CSM) isolées à partir de tissu
adipeux, sur le TSA utilisant des souris modèles d'autisme induit par l'acide valproïque (VPA). Les ASCs
humaines ont été injectées
intraventriculairement chez les ratons nouveau-nés (P2 ou P3) puis nous avons évalué les principaux symptômes
comportementaux des TSA. Les souris
traitées au VPA ont montré une augmentation des comportements répétitifs, une
diminution des interactions sociales et une anxiété accrue, mais ces
comportements autistiques ont été amélioré grâce à la transplantation de
hASCs. En
outre, la transplantation hASCs rétablit l'altération de la phosphatase
et de l'expression de la tensine homolog (PTEN), et le ratio p-AKT/AKT dans le cerveau des souris modèles TSA
induit par VPA. La
baisse du niveau du facteur de croissance endothélial vasculaire (VEGF)
et de l'interleukine 10 (IL-10) par l'APV ont été préservés dans le
cerveau des souris VPA injectées avec l'hASC-. Avec
ces résultats, nous avons expérimentalement montré des effets
thérapeutiques de l'hASCs sur des souris modèles TSA pour la première
fois. Ce système de modèle animal peut être utilisé pour élucider les mécanismes des effets thérapeutiques dans de l'hASCs dans le TSA.
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in social interaction and communication, and patients often display repetitive behaviors. Although the global prevalence of ASD has increased over time, the etiology and treatments for ASD are poorly understood. Recently, some researchers have suggested that stem cells have therapeutic potential for ASD. Thus, in the present study, we investigated the therapeutic effects of human adipose-derived stem cells (hASCs), a kind of mesenchymal stem cells (MSCs) isolated from adipose tissue, on ASD using valproic acid (VPA)-induced autism model mice. Human ASCs were injected into the neonatal pups (P2 or P3) intraventricularly and then we evaluated major behavior symptoms of ASD. VPA-treated mice showed increased repetitive behaviors, decreased social interactions and increased anxiety but these autistic behaviors were ameliorated through transplantation of hASCs. In addition, hASCs transplantation restored the alteration of phosphatase and tensin homolog (PTEN) expression and p-AKT/AKT ratio in the brains of VPA-induced ASD model mice. The decreased level of vascular endothelial growth factor (VEGF) and interleukin 10 (IL-10) by VPA were rescued in the brains of the hASC-injected VPA mice. With these results, we experimentally showed hASCs' therapeutic effects on ASD model mice for the first time. This animal model system can be used to elucidate further mechanisms of therapeutic effects of hASCs in ASD.
Copyright © 2016. Published by Elsevier B.V.
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in social interaction and communication, and patients often display repetitive behaviors. Although the global prevalence of ASD has increased over time, the etiology and treatments for ASD are poorly understood. Recently, some researchers have suggested that stem cells have therapeutic potential for ASD. Thus, in the present study, we investigated the therapeutic effects of human adipose-derived stem cells (hASCs), a kind of mesenchymal stem cells (MSCs) isolated from adipose tissue, on ASD using valproic acid (VPA)-induced autism model mice. Human ASCs were injected into the neonatal pups (P2 or P3) intraventricularly and then we evaluated major behavior symptoms of ASD. VPA-treated mice showed increased repetitive behaviors, decreased social interactions and increased anxiety but these autistic behaviors were ameliorated through transplantation of hASCs. In addition, hASCs transplantation restored the alteration of phosphatase and tensin homolog (PTEN) expression and p-AKT/AKT ratio in the brains of VPA-induced ASD model mice. The decreased level of vascular endothelial growth factor (VEGF) and interleukin 10 (IL-10) by VPA were rescued in the brains of the hASC-injected VPA mice. With these results, we experimentally showed hASCs' therapeutic effects on ASD model mice for the first time. This animal model system can be used to elucidate further mechanisms of therapeutic effects of hASCs in ASD.
Copyright © 2016. Published by Elsevier B.V.
- PMID:27717813
- DOI: 10.1016/j.bbr.2016.10.004