Adipose-derived mesenchymal stem cell-derived exosomes markedly protected the brain against sepsis syndrome induced injury in rat

Chia Lo Chang, Hong-Hwa Chen, Kuan Hung Chen, John Y. Chiang, Yi Chen Li, Hung Sheng Lin, Pei Hsun Sung, Hon Kan Yip

研究成果: Article

摘要

This study tested the hypothesis that sepsis syndrome [SS-induced by cecal-ligation and puncture (CLP)]-induced systemic inflammation and brain damage in rats were effectively suppressed by allogenic adipose-derived mesenchymal stem cell-derived exosome (AMSCEXO). SD rats (n = 72) were divided into group 1 [sham-control (SC)], group 2 (SS only) and group 3 (SS + AMSCEXO) and equally euthanized at 6/24/48/72 h after SS induction, respectively. By 6/16/24/72 h, flow cytometric analyses demonstrated the numbers of inflammatory cells (Ly6G+/CD11b/ c +), immune (CD3+/CD4+ cells/CD3+/CD8+ cells) and early (AN-V+/PI-)/late (AN-V+/PI+) apoptotic cells in circulation were significantly increased in group 2 than in groups 1 and 3, and significantly increased in group 3 than in group 1, whereas the number of T-reg+ cells was significantly progressively increased from groups 1 to 3 (all P < 0.0001). At 6/16/24/72 h, the numbers of (CD3+/CD4+ cells/CD3+/CD8+ cells/T-reg+ cells) in spleen exhibited an identical pattern of circulation among the three groups (all P < 0.0001). ELISA showed inflammatory mediators (IL-6/TNF-α) in circulating/cerebrospinal fluid at 6/24/72 h displayed an identical trend as the immune cells among the three groups (all P < 0.0001). Microscopic findings demonstrated that the cellular expressions of inflammatory (F4/80+//MMP-9+//CD14+//GFPA+) and brain-damaged (AQP4+/γ-H2AX+) biomarkers at 24/72 h exhibited an identical pattern of immune cells among the three groups (all P < 0.0001). The protein expressions of inflammatory (IL-1β/MMP-9/TNF-α/NF-κB/TLR2/TLR-4/MyD88/HMGB1), apoptotic (cleaved-caspase3/PARP/mitochondri-al-Bax) and oxidative-stress (NOX-1/NOX-2/oxidized protein) biomarkers displayed an identical pattern as the immune cells among the three groups (all P < 0.0001). In conclusion, SS elicited vigorously inflammatory reaction not only in circulation but also in spleen/brain, resulting in serious brain damage.

原文English
文章編號AJTR0094885
頁(從 - 到)3955-3971
頁數17
期刊American Journal of Translational Research
11
發行號7
出版狀態Published - 2019 一月 1

指紋

Exosomes
Systemic Inflammatory Response Syndrome
Stem cells
Mesenchymal Stromal Cells
Rats
Brain
Wounds and Injuries
Biomarkers
Matrix Metalloproteinases
HMGB1 Protein
Cerebrospinal fluid
Oxidative stress
Interleukin-1
Interleukin-6
Proteins
Cells
Spleen
Encephalitis
Punctures
Ligation

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Clinical Biochemistry
  • Cancer Research

引用此文

Chang, C. L., Chen, H-H., Chen, K. H., Chiang, J. Y., Li, Y. C., Lin, H. S., ... Yip, H. K. (2019). Adipose-derived mesenchymal stem cell-derived exosomes markedly protected the brain against sepsis syndrome induced injury in rat. American Journal of Translational Research, 11(7), 3955-3971. [AJTR0094885].
Chang, Chia Lo ; Chen, Hong-Hwa ; Chen, Kuan Hung ; Chiang, John Y. ; Li, Yi Chen ; Lin, Hung Sheng ; Sung, Pei Hsun ; Yip, Hon Kan. / Adipose-derived mesenchymal stem cell-derived exosomes markedly protected the brain against sepsis syndrome induced injury in rat. 於: American Journal of Translational Research. 2019 ; 卷 11, 編號 7. 頁 3955-3971.
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title = "Adipose-derived mesenchymal stem cell-derived exosomes markedly protected the brain against sepsis syndrome induced injury in rat",
abstract = "This study tested the hypothesis that sepsis syndrome [SS-induced by cecal-ligation and puncture (CLP)]-induced systemic inflammation and brain damage in rats were effectively suppressed by allogenic adipose-derived mesenchymal stem cell-derived exosome (AMSCEXO). SD rats (n = 72) were divided into group 1 [sham-control (SC)], group 2 (SS only) and group 3 (SS + AMSCEXO) and equally euthanized at 6/24/48/72 h after SS induction, respectively. By 6/16/24/72 h, flow cytometric analyses demonstrated the numbers of inflammatory cells (Ly6G+/CD11b/ c +), immune (CD3+/CD4+ cells/CD3+/CD8+ cells) and early (AN-V+/PI-)/late (AN-V+/PI+) apoptotic cells in circulation were significantly increased in group 2 than in groups 1 and 3, and significantly increased in group 3 than in group 1, whereas the number of T-reg+ cells was significantly progressively increased from groups 1 to 3 (all P < 0.0001). At 6/16/24/72 h, the numbers of (CD3+/CD4+ cells/CD3+/CD8+ cells/T-reg+ cells) in spleen exhibited an identical pattern of circulation among the three groups (all P < 0.0001). ELISA showed inflammatory mediators (IL-6/TNF-α) in circulating/cerebrospinal fluid at 6/24/72 h displayed an identical trend as the immune cells among the three groups (all P < 0.0001). Microscopic findings demonstrated that the cellular expressions of inflammatory (F4/80+//MMP-9+//CD14+//GFPA+) and brain-damaged (AQP4+/γ-H2AX+) biomarkers at 24/72 h exhibited an identical pattern of immune cells among the three groups (all P < 0.0001). The protein expressions of inflammatory (IL-1β/MMP-9/TNF-α/NF-κB/TLR2/TLR-4/MyD88/HMGB1), apoptotic (cleaved-caspase3/PARP/mitochondri-al-Bax) and oxidative-stress (NOX-1/NOX-2/oxidized protein) biomarkers displayed an identical pattern as the immune cells among the three groups (all P < 0.0001). In conclusion, SS elicited vigorously inflammatory reaction not only in circulation but also in spleen/brain, resulting in serious brain damage.",
author = "Chang, {Chia Lo} and Hong-Hwa Chen and Chen, {Kuan Hung} and Chiang, {John Y.} and Li, {Yi Chen} and Lin, {Hung Sheng} and Sung, {Pei Hsun} and Yip, {Hon Kan}",
year = "2019",
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Chang, CL, Chen, H-H, Chen, KH, Chiang, JY, Li, YC, Lin, HS, Sung, PH & Yip, HK 2019, 'Adipose-derived mesenchymal stem cell-derived exosomes markedly protected the brain against sepsis syndrome induced injury in rat', American Journal of Translational Research, 卷 11, 編號 7, AJTR0094885, 頁 3955-3971.

Adipose-derived mesenchymal stem cell-derived exosomes markedly protected the brain against sepsis syndrome induced injury in rat. / Chang, Chia Lo; Chen, Hong-Hwa; Chen, Kuan Hung; Chiang, John Y.; Li, Yi Chen; Lin, Hung Sheng; Sung, Pei Hsun; Yip, Hon Kan.

於: American Journal of Translational Research, 卷 11, 編號 7, AJTR0094885, 01.01.2019, p. 3955-3971.

研究成果: Article

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AU - Chang, Chia Lo

AU - Chen, Hong-Hwa

AU - Chen, Kuan Hung

AU - Chiang, John Y.

AU - Li, Yi Chen

AU - Lin, Hung Sheng

AU - Sung, Pei Hsun

AU - Yip, Hon Kan

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N2 - This study tested the hypothesis that sepsis syndrome [SS-induced by cecal-ligation and puncture (CLP)]-induced systemic inflammation and brain damage in rats were effectively suppressed by allogenic adipose-derived mesenchymal stem cell-derived exosome (AMSCEXO). SD rats (n = 72) were divided into group 1 [sham-control (SC)], group 2 (SS only) and group 3 (SS + AMSCEXO) and equally euthanized at 6/24/48/72 h after SS induction, respectively. By 6/16/24/72 h, flow cytometric analyses demonstrated the numbers of inflammatory cells (Ly6G+/CD11b/ c +), immune (CD3+/CD4+ cells/CD3+/CD8+ cells) and early (AN-V+/PI-)/late (AN-V+/PI+) apoptotic cells in circulation were significantly increased in group 2 than in groups 1 and 3, and significantly increased in group 3 than in group 1, whereas the number of T-reg+ cells was significantly progressively increased from groups 1 to 3 (all P < 0.0001). At 6/16/24/72 h, the numbers of (CD3+/CD4+ cells/CD3+/CD8+ cells/T-reg+ cells) in spleen exhibited an identical pattern of circulation among the three groups (all P < 0.0001). ELISA showed inflammatory mediators (IL-6/TNF-α) in circulating/cerebrospinal fluid at 6/24/72 h displayed an identical trend as the immune cells among the three groups (all P < 0.0001). Microscopic findings demonstrated that the cellular expressions of inflammatory (F4/80+//MMP-9+//CD14+//GFPA+) and brain-damaged (AQP4+/γ-H2AX+) biomarkers at 24/72 h exhibited an identical pattern of immune cells among the three groups (all P < 0.0001). The protein expressions of inflammatory (IL-1β/MMP-9/TNF-α/NF-κB/TLR2/TLR-4/MyD88/HMGB1), apoptotic (cleaved-caspase3/PARP/mitochondri-al-Bax) and oxidative-stress (NOX-1/NOX-2/oxidized protein) biomarkers displayed an identical pattern as the immune cells among the three groups (all P < 0.0001). In conclusion, SS elicited vigorously inflammatory reaction not only in circulation but also in spleen/brain, resulting in serious brain damage.

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