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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

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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.

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Acknowledgments

This study was supported by a grant from the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI14C3484, HI14C2746), by Basic Research Program through the National Research Foundation of South Korea (NRF) funded by the Ministry of Education (NRF-2014R1A2A1A11050576).

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    Authors and Affiliations

    1. Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea

      Sang Eon Park, Jeongmin Lee, Duk L. Na & Jong Wook Chang

    2. Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, Seoul, 06351, Republic of Korea

      Jeongmin Lee, Duk L. Na & Jong Wook Chang

    3. Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea

      Sang Eon Park, Jeongmin Lee & Duk L. Na

    4. Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, 135-710, Republic of Korea

      Sang Eon Park, Jeongmin Lee, Eun Hyuk Chang, Duk L. Na & Jong Wook Chang

    5. Samsung Biomedical Research Institute, Samsung Advanced Institute of Technology (SAIT), Samsung Electronics Co., Ltd., Seoul, 135-710, Republic of Korea

      Eun Hyuk Chang

    6. Department of Obstetrics and Gynecology, Samsung Medical Center, Seoul, Republic of Korea

      Jong Hwa Kim & Ji-Hee Sung

    7. Shanghai Cuvcell Biosciences Co., Ltd., Shanghai, China

      Sang Eon Park

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    Sang Eon Park and Jeongmin Lee have contributed equally.

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    Park, S.E., Lee, J., Chang, E.H. et al. 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. Arch. Pharm. Res. 39, 1171–1179 (2016). https://doi.org/10.1007/s12272-016-0799-4

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    • DOI: https://doi.org/10.1007/s12272-016-0799-4

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