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Multiple systemic transplantations of human amniotic mesenchymal stem cells exert therapeutic effects in an ALS mouse model

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Amyotrophic lateral sclerosis (ALS) is an adult-onset progressive neurodegenerative disease involving degeneration of motor neurons in the central nervous system. Stem cell treatment is a potential therapy for this fatal disorder. The human amniotic membrane (HAM), an extremely rich and easily accessible tissue, has been proposed as an attractive material in cellular therapy and regenerative medicine because of its advantageous characteristics. In the present study, we evaluate the long-term effects of a cellular treatment by intravenous administration of human amniotic mesenchymal stem cells (hAMSCs) derived from HAM into a hSOD1G93A mouse model. The mice received systemic administration of hAMSCs or phosphate-buffered saline (PBS) at the onset, progression and symptomatic stages of the disease. hAMSCs were detected in the spinal cord at the final stage of the disease, in the form of isolates or clusters and were negative for β-tubulin III and GFAP. Compared with the treatment with PBS, multiple hAMSC transplantations significantly retarded disease progression, extended survival, improved motor function, prevented motor neuron loss and decreased neuroinflammation in mice. These findings demonstrate that hAMSC transplantation is a promising cellular treatment for ALS.

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Acknowledgments

This work was supported by grants from Natural Science Foundation of China (81171179, 81272439), Key Sci-Tech Research Projects of Guangdong Province (2008A030201019, S2013020012754), The Laboratory Rolling Projects of Guangdong Provincial Department of Education (2013CXZDA008) to X.D. Jiang; the Talent Program of Yunnan Province, China and The Professorial Fellowship of Monash University to Z.C. Xiao; Scientific and Technological International project of Yunnan province (2013IA013) to Z.L. Hou. We thank the following for their significant contributions: Wen Li for cell transplantation, Yong Yang for CatWalk gaint analysis.

Conflicts of Interest

The authors declare no financial or other competing interests.

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Authors and Affiliations

  1. Department of Neurosurgery, The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China

    Haitao Sun, Peng Li, Lujun Yang, Yuxin Chen, Huihui Chai, Xiaodan Jiang & Zhicheng Xiao

  2. Research Laboratory Center, Yan’an Hospital, Kunming Medical University, Kunming, 650051, China

    Zongliu Hou & Mingyao Meng

  3. Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China

    Huaqiang Yang, Qingjian Zou, Huilin Zhong & Liangxue Lai

  4. The Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, 650228, China

    Zara Zhuyun Yang & Zhicheng Xiao

  5. Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, 3800, Australia

    Zara Zhuyun Yang & Zhicheng Xiao

  6. Model Animal Research Center, Nanjing University, Nanjing, 210061, China

    Jing Zhao

  7. Laboratory of Neurosurgery Institute, Zhujiang Hospital, Southern Medical University, 253# Gongye Road, Guangzhou, 510282, China

    Xiaodan Jiang

  8. Monash Immunology and Stem Cell Labor, Monash University, level 3, Blg 75, Clayton, Victoria, 3800, Australia

    Zhicheng Xiao

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  1. Haitao Sun
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  2. Zongliu Hou
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  3. Huaqiang Yang
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  4. Mingyao Meng
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  7. Lujun Yang
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  8. Yuxin Chen
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  9. Huihui Chai
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  12. Jing Zhao
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  14. Xiaodan Jiang
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  15. Zhicheng Xiao
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Corresponding authors

Correspondence to Xiaodan Jiang or Zhicheng Xiao.

Additional information

Haitao Sun and Zongliu Hou contributed equally to this work.

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Sun, H., Hou, Z., Yang, H. et al. Multiple systemic transplantations of human amniotic mesenchymal stem cells exert therapeutic effects in an ALS mouse model. Cell Tissue Res 357, 571–582 (2014). https://doi.org/10.1007/s00441-014-1903-z

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