Brain-derived neurotrophic factor increases cell number of neural progenitor cells derived from human induced pluripotent stem cells

PeerJ

article

Panetha Pansri¹  Phetcharat Phanthong¹  Nopparat Suthprasertporn³  Yindee Kitiyanant¹  Alisa Tubsuwan⁴  Andras Dinnyes²  Julianna Kobolak²  Narisorn Kitiyanant⁴ 

[1] Department of Anatomy, Faculty of Science, Mahidol University;BioTalentum Ltd.;Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University;Molecular Medical Biosciences Cluster, Institute of Molecular Biosciences, Mahidol University;HCEMM-USZ StemCell Research Group, University of Szeged;Department of Physiology and Animal Health, Hungarian University of Agriculture and Life Sciences

关键词: Brain-derived neurotrophic factor;    Neural progenitor cells;    Induced pluripotent stem cells;    Proliferation;    Alzheimer’s disease;   

DOI  :  10.7717/peerj.11388

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundSeveral pieces of evidence from in vitro studies showed that brain-derived neurotrophic factor (BDNF) promotes proliferation and differentiation of neural stem/progenitor cells (NSCs) into neurons. Moreover, the JAK2 pathway was proposed to be associated with mouse NSC proliferation. BDNF could activate the STAT-3 pathway and induce proliferation in mouse NSCs. However, its effects on proliferation are not fully understood and JAK/STAT pathway was proposed to play a role in this activity.MethodsIn the present study, the effects of BDNF on cell proliferation and neurite outgrowth of Alzheimer’s disease (AD) induced pluripotent stem cells (iPSCs)-derived human neural progenitor cells (hNPCs) were examined. Moreover, a specific signal transduction pathway important in cell proliferation was investigated using a JAK2 inhibitor (AG490) to clarify the role of that pathway.ResultsThe proliferative effect of BDNF was remarkably observed as an increase in Ki-67 positive cells. The cell number of hNPCs was significantly increased after BDNF treatment represented by cellular metabolic activity of the cells measured by MTT assay. This noticeable effect was statistically shown at 20 ng/ml of BDNF treatment. BDNF, however, did not promote neurite outgrowth but increased neuronal cell number. It was found that AG490 suppressed hNPCs proliferation. However, this inhibitor partially decreased BDNF-induced hNPCs proliferation. These results demonstrated the potential role of BDNF for the amelioration of AD through the increase of AD-derived hNPCs number.

【 授权许可】

CC BY