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BMP4: a possible key factor in differentiation of auditory neuron-like cells from bone-derived mesenchymal stromal cells

  • Background: Previous studies have shown that BMP4 may play an important part in the development of auditory neurons (ANs), which are degenerated in sensorineural hearing loss. However, whether BMP4 can promote sensory fate specification from mesenchymal stromal cells (MSCs) is unknown so far. Methods: MSCs isolated from Sprague-Dawley (SD) rats were confirmed by expression of MSC markers using flow cytometry and adipogenesis/osteogenesis using differentiation assays. MSCs treated with a complex of neurotrophic factors (BMP4 group and non-BMP4 group) were induced into auditory neuron-like cells, then the differences between the two groups were analyzed in morphological observation, cell growth curve, qRT-PCR, and immunofluorescence. Results: Flow cytometric analysis showed that the isolated cells expressed typical MSC surface markers. After adipogenic and osteogenic induction, the cells were stained by oil red O and Alizarin Red. The neuronal induced cells were in the growth plateau and had special forms of neurons. In the presenceBackground: Previous studies have shown that BMP4 may play an important part in the development of auditory neurons (ANs), which are degenerated in sensorineural hearing loss. However, whether BMP4 can promote sensory fate specification from mesenchymal stromal cells (MSCs) is unknown so far. Methods: MSCs isolated from Sprague-Dawley (SD) rats were confirmed by expression of MSC markers using flow cytometry and adipogenesis/osteogenesis using differentiation assays. MSCs treated with a complex of neurotrophic factors (BMP4 group and non-BMP4 group) were induced into auditory neuron-like cells, then the differences between the two groups were analyzed in morphological observation, cell growth curve, qRT-PCR, and immunofluorescence. Results: Flow cytometric analysis showed that the isolated cells expressed typical MSC surface markers. After adipogenic and osteogenic induction, the cells were stained by oil red O and Alizarin Red. The neuronal induced cells were in the growth plateau and had special forms of neurons. In the presence of BMP4, the inner ear genes NF-M, Neurog1, GluR4, NeuroD, Calretinin, NeuN, Tau, and GATA3 were up-regulated in MSCs. Conclusions: MSCs have the capacity to differentiate into auditory neuron-like cells in vitro. As an effective inducer, BMP4 may play a key role in transdifferentiation.show moreshow less

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Author:Tao Peng, Ganghua Zhu, Yunpeng Dong, Junjie Zeng, Wei Li, Weiwei Guo, Yong Chen, Maoli Duan, Berthold HocherGND, Dinghua Xie
DOI:https://doi.org/10.7754/Clin.Lab.2015.150217
ISSN:1433-6510 (print)
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=26634236
Parent Title (English):Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion
Publisher:Clin Lab Publ., Verl. Klinisches Labor
Place of publication:Heidelberg
Document Type:Article
Language:English
Year of first Publication:2015
Year of Completion:2015
Release Date:2017/03/27
Tag:BMP4; auditory neurons; differentiation
Volume:61
Issue:9
Pagenumber:8
First Page:1171
Last Page:1178
Funder:National Basic Research Program of China (973) [2012CB967904, 2012CB967900]; Cochlear Implantation Program of Hunan, China; ALF, Tysta skolan abd Karolinska Institutet
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft
Peer Review:Referiert