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Electro-Acupuncture Promotes the Survival and Differentiation of Transplanted Bone Marrow Mesenchymal Stem Cells Pre-Induced with Neurotrophin-3 and Retinoic Acid in Gelatin Sponge Scaffold after Rat Spinal Cord Transection

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Abstract

In the past decades, mesenchymal stem cells (MSCs) as a promising cell candidate have received the most attention in the treatment of spinal cord injury (SCI). However, due to the low survival rate and low neural differentiation rate, the grafted MSCs do not perform well as one would have expected. In the present study, we tested a combinational therapy to improve on this situation. MSCs were loaded into three-dimensional gelatin sponge (GS) scaffold. After 7 days of induction with neurotrophin-3 (NT-3) and retinoic acid (RA) in vitro, we observed a significant increase in TrkC mRNA transcription by Real-time PCR and this was confirmed by in situ hybridization. The expression of TrkC was also confirmed by Western blot and immunohistochemistry. Differentiation potential of MSCs in vitro into neuron-like cells or oligodendrocyte-like cells was further demonstrated by using immunofluorescence staining. The pre-induced MSCs seeding in GS scaffolds were then grafted into the transected rat spinal cord. One day after grafting, Governor Vessel electro-acupuncture (GV-EA) treatment was applied to rats in the NR-MSCs + EA group. At 30 days after GV-EA treatment, it found that the grafted MSCs have better survival rate and neuron-like cell differentiation compared with those without GV-EA treatment. The sustained TrkC expression in the grafted MSCs as well as increased NT-3 content in the injury/graft site by GV-EA suggests that NT-3/TrkC signaling pathway may be involved in the promoting effect. This study demonstrates that GV-EA and pre-induction with NT-3 and RA together may promote the survival and differentiation of grafted MSCs in GS scaffold in rat SCI.

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Acknowledgments

This study was supported by grants from the Chinese National Natural Science Foundation (No. 81330028; U1301223), National 863 Project (No. 2013AA020106), Foundation of the Education Ministry of China (201300193035), Foundation of Guangdong Province (No. 2011A030300004), and Foundation of Guangzhou City (No. 2012 J4100077) to Y.S. Zeng.

Conflict of Interest

The authors declare no potential conflicts of interest.

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Authors and Affiliations

  1. Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, 74# Zhongshan 2nd Road, Guangzhou, 510080, China

    Ke Zhang, Zhou Liu, Li-Na Qin, Ying Ding & Yuan-Shan Zeng

  2. Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-sen University), Ministry of Education, 74# Zhongshan 2nd Road, Guangzhou, 510080, China

    Ge Li, Bi-Qin Lai & Yuan-Shan Zeng

  3. Institute of Spinal Cord Injury, Sun Yat-sen University, Guangzhou, China

    Yuan-Shan Zeng

  4. Department of Acupuncture of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China

    Jing-Wen Ruan

  5. Spinal Cord Society Research Center, 80526, Fort Collins, CO, USA

    Shu-Xin Zhang

  6. Co-innovation Center of Neuroregeneration, Jiangsu, China

    Yuan-Shan Zeng

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  1. Ke Zhang
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  2. Zhou Liu
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Zhang, K., Liu, Z., Li, G. et al. Electro-Acupuncture Promotes the Survival and Differentiation of Transplanted Bone Marrow Mesenchymal Stem Cells Pre-Induced with Neurotrophin-3 and Retinoic Acid in Gelatin Sponge Scaffold after Rat Spinal Cord Transection. Stem Cell Rev and Rep 10, 612–625 (2014). https://doi.org/10.1007/s12015-014-9513-4

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