title: Human adipose-derived stem cells ameliorate repetitive behavior, social deficit and anxiety in a VPA-induced autism mouse model.
abstract: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in social interaction and communication, and patients often display co-occurring 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 autologous mesenchymal stem cells (MSCs) isolated from adipose tissue, on 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 found hASCs' therapeutic effects on autistic phenotypes in a 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.
authors.affiliation: Department of Pharmacology, College of Medicine and Neuroscience Research Institute, Gachon University, Incheon 406-799, Republic of Korea; Department of Pharmacology, College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sungji
authors.initials: S
authors.lastname: Ha
authors.affiliation: Department of Pharmacology, College of Medicine and Neuroscience Research Institute, Gachon University, Incheon 406-799, Republic of Korea.
authors.forename: Hyunjun
authors.initials: H
authors.lastname: Park
authors.affiliation: Department of Pharmacology, College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Usman
authors.initials: U
authors.lastname: Mahmood
authors.affiliation: Stem Cell Research Center, K stem cell Co., Ltd., Seoul, Republic of Korea.
authors.forename: Jeong Chan
authors.initials: JC
authors.lastname: Ra
authors.affiliation: Department of Pharmacology, College of Medicine and Neuroscience Research Institute, Gachon University, Incheon 406-799, Republic of Korea. Electronic address: yhsuh@gachon.ac.kr.
authors.forename: Yoo-Hun
authors.initials: YH
authors.lastname: Suh
authors.affiliation: Department of Pharmacology, College of Medicine and Neuroscience Research Institute, Gachon University, Incheon 406-799, Republic of Korea. Electronic address: kachang74@gmail.com.
authors.forename: Keun-A
authors.initials: KA
authors.lastname: Chang
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000209:etiology / Q000601:surgery*; D001321:Autistic Disorder / Q000139:chemically induced / Q000150:complications* / Q000601:surgery; D012090:Cumulative Trauma Disorders / Q000209:etiology / Q000601:surgery*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D051058:Oncogene Protein v-akt / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000503:physiopathology*; D012920:Social Behavior Disorders / Q000209:etiology / Q000601:surgery*; D014635:Valproic Acid / Q000633:toxicity; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10; D014635:Valproic Acid; D051058:Oncogene Protein v-akt
keywords: Adipose-derived stem cell; Autism spectrum disorder; Stem cell therapy; Valproic acid