Chitosan scaffolds induce human dental pulp stem cells to neural differentiation: potential roles for spinal cord injury therapy

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Abstract

Cell-based transplantation strategies hold great potential for spinal cord injury (SCI) repair. Chitosan scaffolds have therapeutic benefits for spinal cord regeneration. Human dental pulp stem cells (DPSCs) are abundant available stem cells with low immunological incompatibility and can be considered for cell replacement therapy. The purpose of this study is to investigate the role of chitosan scaffolds in the neural differentiation of DPSCs in vitro and to assess the supportive effects of chitosan scaffolds in an animal model of SCI. DPSCs were incubated with chitosan scaffolds. Cell viability and the secretion of neurotrophic factors were analyzed. DPSCs incubated with chitosan scaffolds were treated with neural differentiation medium for 14 days and then neural genes and protein markers were analyzed by Western blot and reverse transcription plus the polymerase chain reaction. Our study revealed a higher cell viability and neural differentiation in the DPSC/chitosan-scaffold group. Compared with the control group, the levels of BDNF, GDNF, b-NGF, and NT-3 were significantly increased in the DPSC/chitosan-scaffold group. The Wnt/β-catenin signaling pathway played a key role in the neural differentiation of DPSCs combined with chitosan scaffolds. Transplantation of DPSCs together with chitosan scaffolds into an SCI rat model resulted in the marked recovery of hind limb locomotor functions. Thus, chitosan scaffolds were non-cytotoxic and provided a conducive and favorable microenvironment for the survival and neural differentiation of DPSCs. Transplantation of DPSCs might therefore be a suitable candidate for treating SCI and other neuronal degenerative diseases.

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Corresponding authors

Correspondence to Xingmei Feng or Zhiming Cui.

Additional information

Jinlong Zhang, Xiaohui Lu, and Guijuan Feng contributed equally to this work.

This work was supported by Natural Science Foundation of China Grant (nos. 81500809, 81501076), Jiangsu Natural Science Foundation (BK2011385), “Top Six Types of Talents” Financial Assistance of Jiangsu Province Grant (no. 2013-WSN-076), Graduate Student Innovation of Science and Technology Projects in Jiangsu Province and in Nantong University (nos.SJLX-0588, SJLX-0588) and Nantong Natural Science Foundation (no. BK2014038).

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Zhang, J., Lu, X., Feng, G. et al. Chitosan scaffolds induce human dental pulp stem cells to neural differentiation: potential roles for spinal cord injury therapy. Cell Tissue Res 366, 129–142 (2016). https://doi.org/10.1007/s00441-016-2402-1

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Keywords

  • Dental pulp stem cells (DPSCs)
  • Neural differentiation
  • Wnt/β-catenin
  • Chitosan scaffolds
  • Spinal cord injury (SCI)