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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

邮发代号 80-967

2019 Impact Factor: 3.421

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Frontiers of Medicine  2022, Vol. 16 Issue (3): 429-441   https://doi.org/10.1007/s11684-021-0842-9
  本期目录
Quantitative proteomics revealed extensive microenvironmental changes after stem cell transplantation in ischemic stroke
Yao Chen1,2,3,7, Fahuan Song1,2,3, Mengjiao Tu1,2,3,8, Shuang Wu1,2,3, Xiao He1,2,3, Hao Liu1,2,3, Caiyun Xu1,2,3, Kai Zhang1,2,3, Yuankai Zhu1,2,3, Rui Zhou1,2,3, Chentao Jin1,2,3, Ping Wang5,6, Hong Zhang1,2,3,4,5,6(), Mei Tian1,2,3()
1. Department of Nuclear Medicine and Medical PET Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
2. Institute of Nuclear Medicine and Molecular Imaging, Zhejiang University, Hangzhou 310009, China
3. Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou 310009, China
4. Shanxi Medical University, Taiyuan 030001, China
5. Key Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou 310027, China​
6. College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou 310027, China
7. Department of Radiology, Zhejiang Hospital, Hangzhou 310030, China
8. Department of PET Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
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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.
Key words： ischemic stroke    microenvironment    induced pluripotent stem cells (iPSCs)    positron emission tomography (PET)    quantitative proteomics
收稿日期: 2020-07-29      出版日期: 2022-07-18
Corresponding Author(s): Hong Zhang,Mei Tian   
 引用本文:   
. [J]. Frontiers of Medicine, 2022, 16(3): 429-441.
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, Mei Tian. Quantitative proteomics revealed extensive microenvironmental changes after stem cell transplantation in ischemic stroke. Front. Med., 2022, 16(3): 429-441.
 链接本文:  
https://academic.hep.com.cn/fmd/CN/10.1007/s11684-021-0842-9
https://academic.hep.com.cn/fmd/CN/Y2022/V16/I3/429
Fig.1  
Fig.2  
Fig.3  
Fig.4  
UniProt ID Gene symbol Protein name Ratio (iPSCs/PBS) P value
Neuronal survival
Q4QQV8 Chmp5 Charged multivesicular body protein 5a 2.00 0.03
Q01986 Map2k1 Dual specificity mitogen-activated protein kinase kinase 1b 1.22 0.02
B1WBW4 Armc10 Armadillo repeat-containing protein 10a 0.68 0.03
P04775 Scn2a Sodium channel protein type 2 subunit αb 0.77 0.01
G3V7J1 Clstn3 Calsyntenin-3b 0.78 0.02
Q5M7A7 Cnrip1 CB1 cannabinoid receptor-interacting protein 1a 0.82 0.01
F1LP76 Ikbkap Elongator complex protein 1b 0.83 0.01
Axonal remodeling
P22057 Ptgds Prostaglandin-H2 D-isomerasea 1.72 0.04
Q6J4I0 Ppp1r1b Protein phosphatase 1 regulatory subunit 1Ba 1.41 0.00
Q562C6 Lztfl1 Leucine zipper transcription factor-like protein 1a 1.20 0.00
F1LP34 Anp32b Acidic leucine-rich nuclear phosphoprotein 32 family member Bb 0.81 0.03
P47875 Csrp1 Cysteine and glycine-rich protein 1a 0.83 0.01
Mitochondrial function
Q62760 Tomm20 Mitochondrial import receptor subunit TOM20 homologa 1.32 0.04
Q4QRB0 Gale Galactose-4-epimerase, UDP, isoform CRA_aa 1.31 0.01
A0A0G2JSR6 Gng7 Guanine nucleotide binding protein G(I)/G(S)/G(O) subunit γ-7a 1.22 0.00
P32089 Slc25a1 Tricarboxylate transport protein, mitochondrialb 1.20 0.01
G3V9J7 Rabep1 RabGTPase binding effector protein 1b 0.79 0.02
A0A096MIV5 Abcf2 Protein Abcf2b 0.81 0.03
G3V784 Adpgk ADP-dependent glucokinase, isoform CRA_ab 0.81 0.04
Q5RKH2 Galk1 Galactokinase 1b 0.83 0.02
Oxidative stress
D3ZCZ9 LOC100912599 NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrialb 1.27 0.03
Q3KRD8 Eif6 Eukaryotic translation initiation factor 6b 0.80 0.04
Q6AXX6 Fam213a Redox-regulatory protein FAM213Aa 0.82 0.01
Q6AXX5 Rdh11 Protein Rdh11b 0.82 0.03
Others/unknown
A1L114 Fga Fga proteina 1.70 0.01
P14480 Fgb Fibrinogen beta chaina 1.65 0.02
D4A250 RGD1563620 Protein RGD1563620b 1.41 0.01
A0A0G2QC17 Pdp1 Protein phosphatase 2C, magnesium dependent, catalytic subunit, isoform CRA_aa 1.36 0.03
Q63041 A1m α-1-macroglobulina 1.36 0.04
Q68FY4 Gc Group specific componenta 1.34 0.00
A0A0G2JUR5 Mprip Myosin phosphatase Rho-interacting proteina 1.27 0.02
M0RCT5 Eml1 Echinoderm microtubule-associated protein-like 1a 1.21 0.03
D3ZWW5 Slc30a9 Protein Slc30a9a 1.21 0.04
Q80X08 Fam21 WASH complex subunit FAM21b 0.70 0.04
Q6PDU6 Hbb β-gloa 0.70 0.02
A0A0G2JXY6 Scn1b Sodium channel subunit β-1b 0.76 0.04
A0A0G2K5H2 Clvs1 Clavesin-1b 0.79 0.00
P84039 Enpp5 Ectonucleotidepyrophosphatase/phosphodiesterase family member 5b 0.82 0.00
F1M3P6 Scai Protein Scaia 0.82 0.02
Tab.1  
Fig.5  
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