Inhibitory effect of mesenchymal stem cell-derived exosomes on the activation of hippocampal astrocytes

doi:10.3877/cma.j.issn.2095-1221.2021.02.005

Abstract

Abstract:

Objective

To investigate the inhibitory role of mesenchymal stem cells-derived exosomes (MSC-Exo) in the activation of hippocampal astrocytes.

Methods

Exosomes were isolated from umbilical cord MSCs by ultra-speed centrifugation, and labeled by PKH-26 dye. The primary hippocampal astrocytes were pretreated with MSC-Exo and then stimulated by lipopolysaccharide (LPS) to induce cell activation, as well as divided into control group, LPS group and LPS+MSC- Exo group. Immunocytochemistry and immunoblotting were used to detect the expression of C3 and GFAP, and ELISA was used to test the expression of interleukin (IL) -1β, tumor necrosis factor (TNF) -α and IL- 6. One way ANOVA and least significant difference (LSD) test were used for statistical analysis.

Results

The results showed that the MSC-Exo presented normal biological characteristics of exosomes, as well as exhibited the capacity to integrate into the soma and processes of astrocytes. Compared with the control group, the expression of glial fibrillary acidic protein (GFAP) (1.47±0.15 vs 0.95±0.17, P < 0.01) , A1 phenotype of astrocyte marker C3 (1.32±0.23 vs 0.87±0.16, P < 0.05) , IL-1β [ (282.90±5.13) pg/ mL vs (252.53±5.51) pg/mL, P < 0.05], TNF-α [ (128.26±1.89) pg/mL vs (111.86±2.84) pg/mL, P < 0.01] and IL-6 [ (180.95±3.16) pg/mL vs (163.95±3.71) pg/mL, P < 0.05] were significantly increased after stimulation with LPS. The pre-treatment with MSC-Exo could reduce the expression of GFAP (0.97±0.16 vs 1.47±0.15, P < 0.01) , C3 (0.83±0.12 vs 1.32±0.23, P < 0.01) , IL-1β [ (262.20±2.64) pg/mL vs (282.90±5.13) pg/mL, P < 0.05], and TNF-α [ (120.79±0.42) pg/mL vs (128.26±1.89) pg/mL, P < 0.05], but there was no significant change of IL-6 [ (187.2±0.64) pg/mL vs (180.9±3.16) pg/mL, P > 0.05].

Conclusion

MSC-Exo has inhibitory effect on the activation of hippocampal astrocytes.

Key words: Mesenchymal stem cells, Exosomes, Astrocytes, Inflammatory response, Cell activation

Dongjing Zhu, Panpan Xian, Tian Wang, Zhongzheng He, Yanping Yang, Fei Xie, Qianfa Long. Inhibitory effect of mesenchymal stem cell-derived exosomes on the activation of hippocampal astrocytes[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2021, 11(02): 99-105.

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URL: https://zhxbygxbzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-1221.2021.02.005

https://zhxbygxbzz.cma-cmc.com.cn/EN/Y2021/V11/I02/99

Figures/Tables 9

References 14

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分组	实验次数	GFAP	C3
对照	3	0.95±0.17	0.87±0.16
LPS	3	1.47±0.15 ^a	1.32±0.23 ^a
LPS+MSC-Exo	3	0.97±0.16 ^b	0.83±0.12 ^b
F值		10.150	7.172
P值		0.012	0.026

分组	实验次数	GFAP	C3
对照	3	0.95±0.17	0.87±0.16
LPS	3	1.47±0.15 ^a	1.32±0.23 ^a
LPS+MSC-Exo	3	0.97±0.16 ^b	0.83±0.12 ^b
F值		10.150	7.172
P值		0.012	0.026

分组	实验次数	IL-1β	TNF-α	IL-6
对照	3	252.53 ± 5.51	111.86 ± 2.84	163.95 ± 3.71
LPS	3	282.90 ± 5.13^a	128.26 ± 1.89^a	180.95 ± 3.16^a
LPS+MSC-Exo	3	262.20 ± 2.64^b	120.79 ± 0.42^b	187.25 ± 0.64
F值		11.342	17.215	18.057
P值		0.009	0.003	0.003

分组	实验次数	IL-1β	TNF-α	IL-6
对照	3	252.53 ± 5.51	111.86 ± 2.84	163.95 ± 3.71
LPS	3	282.90 ± 5.13^a	128.26 ± 1.89^a	180.95 ± 3.16^a
LPS+MSC-Exo	3	262.20 ± 2.64^b	120.79 ± 0.42^b	187.25 ± 0.64
F值		11.342	17.215	18.057
P值		0.009	0.003	0.003

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