title: Activin A secreted by human mesenchymal stem cells induces neuronal development and neurite outgrowth in an in vitro model of Alzheimer's disease: neurogenesis induced by MSCs via activin A.
abstract: Alzheimer's disease (AD) is characterized by progressive loss of memory in addition to cortical atrophy. Cortical atrophy in AD brains begins in the parietal and temporal lobes, which are near the subventricular zone (SVZ). The aim of this study was to activate the neurogenesis in the SVZ of AD brains by human mesenchymal stem cells (hMSCs). Neural stem cells (NSCs) were isolated from SVZ of 4-month-old 5XFAD mice. Co-culture of hMSCs with SVZ-derived NSCs from 5XFAD mice induced neuronal development and neurite outgrowth. To examine the inducing factor of neurogenesis, human cytokine array was performed with co-cultured media, and revealed elevated release of activin A from hMSCs. Also, we confirmed that the mRNA levels of activin A and activin receptor in the SVZ of 5XFAD mice were significantly lower than normal mice. Treatment of human recombinant activin A in SVZ-derived NSCs from 5XFAD mice induced neuronal development and neurite outgrowth. These data suggest that use of hMSCs and activin A to recover neurogenesis in future studies of cortical regeneration to treat AD.
authors: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea.|Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea.|Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, 135-710, Republic of Korea.|Shanghai Cuvcell Biosciences Co., Ltd., Shanghai, China.
authors: Sang Eon
authors: SE
authors: Park
authors: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea.|Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, Seoul, 06351, Republic of Korea.|Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea.|Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, 135-710, Republic of Korea.
authors: Jeongmin
authors: J
authors: Lee
authors: Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, 135-710, Republic of Korea.|Samsung Biomedical Research Institute, Samsung Advanced Institute of Technology (SAIT), Samsung Electronics Co., Ltd., Seoul, 135-710, Republic of Korea.
authors: Eun Hyuk
authors: EH
authors: Chang
authors: Department of Obstetrics and Gynecology, Samsung Medical Center, Seoul, Republic of Korea.
authors: Jong Hwa
authors: JH
authors: Kim
authors: Department of Obstetrics and Gynecology, Samsung Medical Center, Seoul, Republic of Korea.
authors: Ji-Hee
authors: JH
authors: Sung
authors: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea. dukna@skku.edu.|Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, Seoul, 06351, Republic of Korea. dukna@skku.edu.|Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea. dukna@skku.edu.|Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, 135-710, Republic of Korea. dukna@skku.edu.
authors: Duk L
authors: DL
authors: Na
authors: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea. jongwook.chang@samsung.com.|Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, Seoul, 06351, Republic of Korea. jongwook.chang@samsung.com.|Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, 135-710, Republic of Korea. jongwook.chang@samsung.com.
authors: Jong Wook
authors: JW
authors: Chang
mesh_terms: D028341:Activins / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D016501:Neurites / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D000071446:Neuronal Outgrowth / Q000502:physiology*
chemical_list: C422405:activin A; D028341:Activins
keywords: 5XFAD; Activin A; Alzheimer’s disease; Neurite outgrowth; Neuronal development; SVZ-derived NSCs; hMSC