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.
| Original language | English |
|---|---|
| Article number | AJTR0094885 |
| Pages (from-to) | 3955-3971 |
| Number of pages | 17 |
| Journal | American Journal of Translational Research |
| Volume | 11 |
| Issue number | 7 |
| Publication status | Published - 2019 Jan 1 |
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All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Clinical Biochemistry
- Cancer Research
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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.
In: American Journal of Translational Research, Vol. 11, No. 7, AJTR0094885, 01.01.2019, p. 3955-3971.Research output: Contribution to journal › Article
TY - JOUR
T1 - Adipose-derived mesenchymal stem cell-derived exosomes markedly protected the brain against sepsis syndrome induced injury in rat
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
PY - 2019/1/1
Y1 - 2019/1/1
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85070558623&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85070558623&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:85070558623
VL - 11
SP - 3955
EP - 3971
JO - American Journal of Translational Research
JF - American Journal of Translational Research
SN - 1943-8141
IS - 7
M1 - AJTR0094885
ER -