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Quantitative proteomics revealed extensive microenvironmental changes after stem cell transplantation in ischemic stroke

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Abstract

The local microenvironment is essential to stem cell-based therapy for ischemic stroke, and spatiotemporal changes of the microenvironment in the pathological process provide vital clues for understanding the therapeutic mechanisms. However, relevant studies on microenvironmental changes were mainly confined in the acute phase of stroke, and long-term changes remain unclear. This study aimed to investigate the microenvironmental changes in the subacute and chronic phases of ischemic stroke after stem cell transplantation. Herein, induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) were transplanted into the ischemic brain established by middle cerebral artery occlusion surgery. Positron emission tomography imaging and neurological tests were applied to evaluate the metabolic and neurofunctional alterations of rats transplanted with stem cells. Quantitative proteomics was employed to investigate the protein expression profiles in iPSCs-transplanted brain in the subacute and chronic phases of stroke. Compared with NSCs-transplanted rats, significantly increased glucose metabolism and neurofunctional scores were observed in iPSCs-transplanted rats. Subsequent proteomic data of iPSCs-transplanted rats identified a total of 39 differentially expressed proteins in the subacute and chronic phases, which are involved in various ischemic stroke-related biological processes, including neuronal survival, axonal remodeling, antioxidative stress, and mitochondrial function restoration. Taken together, our study indicated that iPSCs have a positive therapeutic effect in ischemic stroke and emphasized the wide-ranging microenvironmental changes in the subacute and chronic phases.

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Acknowledgements

We thank Dr. Weizhong Gu for his excellent technical assistance and expert advice on HE staining and Western blot analysis. Mass spectrometry analysis was performed in Jingjie PTM Biolab (Hangzhou) Co., Ltd. This work is sponsored by the National Key Research and Development Program of China (No. 2016YFA0100-900) and the Fund for Shanxi “1331 Project” Key Innovative Research Team.

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine and Medical PET Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China

    Yao Chen, Fahuan Song, Mengjiao Tu, Shuang Wu, Xiao He, Hao Liu, Caiyun Xu, Kai Zhang, Yuankai Zhu, Rui Zhou, Chentao Jin, Hong Zhang & Mei Tian

  2. Institute of Nuclear Medicine and Molecular Imaging, Zhejiang University, Hangzhou, 310009, China

    Yao Chen, Fahuan Song, Mengjiao Tu, Shuang Wu, Xiao He, Hao Liu, Caiyun Xu, Kai Zhang, Yuankai Zhu, Rui Zhou, Chentao Jin, Hong Zhang & Mei Tian

  3. Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, 310009, China

    Yao Chen, Fahuan Song, Mengjiao Tu, Shuang Wu, Xiao He, Hao Liu, Caiyun Xu, Kai Zhang, Yuankai Zhu, Rui Zhou, Chentao Jin, Hong Zhang & Mei Tian

  4. Shanxi Medical University, Taiyuan, 030001, China

    Hong Zhang

  5. Key Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou, 310027, China

    Ping Wang & Hong Zhang

  6. College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, 310027, China

    Ping Wang & Hong Zhang

  7. Department of Radiology, Zhejiang Hospital, Hangzhou, 310030, China

    Yao Chen

  8. Department of PET Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China

    Mengjiao Tu

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  1. Yao Chen
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  2. Fahuan Song
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  13. Hong Zhang
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Correspondence to Hong Zhang or Mei Tian.

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Yao Chen, Fahuan Song, Mengjiao Tu, Shuang Wu, Xiao He, Hao Liu, Caiyun Xu, Kai Zhang, Yuankai Zhu, Rui Zhou, Chentao Jin, Ping Wang, Hong Zhang, and Mei Tian claim that there are no conflicts of interest. All institutional and national guidelines for the care and use of laboratory animals were followed.

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Chen, Y., Song, F., Tu, M. et al. Quantitative proteomics revealed extensive microenvironmental changes after stem cell transplantation in ischemic stroke. Front. Med. 16, 429–441 (2022). https://doi.org/10.1007/s11684-021-0842-9

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