IL-1β Pretreatment Improves the Efficacy of Mesenchymal Stem Cells on Acute Liver Failure by Enhancing CXCR4 Expression
Background. Mesenchymal stem cells (MSCs), with the powerful metabolic and functional supporting abilities for inflammatory diseases, may be an effective therapeutic strategy for acute liver failure (ALF). However, the efficacy of MSCs can still be promoted if pretreatment is applied to enhance thei...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-01-01
|
| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2020/1498315 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832568589234733056 |
|---|---|
| author | He Nie Fangmei An Jie Mei Cheng Yang Qiang Zhan Qinglin Zhang |
| author_facet | He Nie Fangmei An Jie Mei Cheng Yang Qiang Zhan Qinglin Zhang |
| author_sort | He Nie |
| collection | DOAJ |
| description | Background. Mesenchymal stem cells (MSCs), with the powerful metabolic and functional supporting abilities for inflammatory diseases, may be an effective therapeutic strategy for acute liver failure (ALF). However, the efficacy of MSCs can still be promoted if pretreatment is applied to enhance their poor migration towards the damaged liver. The purpose of this study is to determine the effect of IL-1β pretreatment on the efficacy and homing ability of MSCs in ALF. Methods. MSCs were isolated by the whole bone marrow adherence method and characterized. The efficacy and homing ability of IL-1β-pretreated MSCs (Pre-MSCs) were examined in a rat ALF model and compared with that of MSCs and normal saline. Then, Western blot was performed to detect the c-Met and CXCR4 expression of MSCs and Pre-MSCs and followed by flow cytometry to detect the meaningful indicators. Finally, the migration abilities of different cells and different conditions were tested by the Transwell migration assay. Results. MSCs of ideal purity were successfully isolated and cultured. Comparing with MSCs, Pre-MSCs had significantly better efficacy on improving the survival rate and liver function of ALF rats. Further analyses of damaged liver tissues showed that IL-1β pretreatment significantly enhanced the efficacy of MSCs on suppressing liver necrosis. Besides, Pre-MSCs exhibited better effects in inhibiting apoptosis and activating proliferation. The results of tracing experiments with CM-Dil-labeled cells confirmed that more cells migrated to the damaged liver in the Pre-MSC group. In terms of mechanism, the CXCR4 expression was significantly enhanced by IL-1β pretreatment, and an increased migration ability towards SDF-1 that could be reversed by AMD3100 was found in Pre-MSCs. Conclusion. IL-1β pretreatment could enhance the homing ability of MSCs at least partially by increasing the expression of CXCR4 and further improve the efficacy of MSCs on ALF. |
| format | Article |
| id | doaj-art-9fdccb6dbe4845a0acb6d6d3f497358a |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-9fdccb6dbe4845a0acb6d6d3f497358a2025-02-03T00:58:44ZengWileyStem Cells International1687-966X1687-96782020-01-01202010.1155/2020/14983151498315IL-1β Pretreatment Improves the Efficacy of Mesenchymal Stem Cells on Acute Liver Failure by Enhancing CXCR4 ExpressionHe Nie0Fangmei An1Jie Mei2Cheng Yang3Qiang Zhan4Qinglin Zhang5Department of Gastroenterology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, ChinaDepartment of Gastroenterology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, ChinaDepartment of Oncology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi 214023, ChinaDepartment of Gastroenterology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, ChinaDepartment of Gastroenterology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, ChinaDepartment of Gastroenterology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, ChinaBackground. Mesenchymal stem cells (MSCs), with the powerful metabolic and functional supporting abilities for inflammatory diseases, may be an effective therapeutic strategy for acute liver failure (ALF). However, the efficacy of MSCs can still be promoted if pretreatment is applied to enhance their poor migration towards the damaged liver. The purpose of this study is to determine the effect of IL-1β pretreatment on the efficacy and homing ability of MSCs in ALF. Methods. MSCs were isolated by the whole bone marrow adherence method and characterized. The efficacy and homing ability of IL-1β-pretreated MSCs (Pre-MSCs) were examined in a rat ALF model and compared with that of MSCs and normal saline. Then, Western blot was performed to detect the c-Met and CXCR4 expression of MSCs and Pre-MSCs and followed by flow cytometry to detect the meaningful indicators. Finally, the migration abilities of different cells and different conditions were tested by the Transwell migration assay. Results. MSCs of ideal purity were successfully isolated and cultured. Comparing with MSCs, Pre-MSCs had significantly better efficacy on improving the survival rate and liver function of ALF rats. Further analyses of damaged liver tissues showed that IL-1β pretreatment significantly enhanced the efficacy of MSCs on suppressing liver necrosis. Besides, Pre-MSCs exhibited better effects in inhibiting apoptosis and activating proliferation. The results of tracing experiments with CM-Dil-labeled cells confirmed that more cells migrated to the damaged liver in the Pre-MSC group. In terms of mechanism, the CXCR4 expression was significantly enhanced by IL-1β pretreatment, and an increased migration ability towards SDF-1 that could be reversed by AMD3100 was found in Pre-MSCs. Conclusion. IL-1β pretreatment could enhance the homing ability of MSCs at least partially by increasing the expression of CXCR4 and further improve the efficacy of MSCs on ALF.http://dx.doi.org/10.1155/2020/1498315 |
| spellingShingle | He Nie Fangmei An Jie Mei Cheng Yang Qiang Zhan Qinglin Zhang IL-1β Pretreatment Improves the Efficacy of Mesenchymal Stem Cells on Acute Liver Failure by Enhancing CXCR4 Expression Stem Cells International |
| title | IL-1β Pretreatment Improves the Efficacy of Mesenchymal Stem Cells on Acute Liver Failure by Enhancing CXCR4 Expression |
| title_full | IL-1β Pretreatment Improves the Efficacy of Mesenchymal Stem Cells on Acute Liver Failure by Enhancing CXCR4 Expression |
| title_fullStr | IL-1β Pretreatment Improves the Efficacy of Mesenchymal Stem Cells on Acute Liver Failure by Enhancing CXCR4 Expression |
| title_full_unstemmed | IL-1β Pretreatment Improves the Efficacy of Mesenchymal Stem Cells on Acute Liver Failure by Enhancing CXCR4 Expression |
| title_short | IL-1β Pretreatment Improves the Efficacy of Mesenchymal Stem Cells on Acute Liver Failure by Enhancing CXCR4 Expression |
| title_sort | il 1β pretreatment improves the efficacy of mesenchymal stem cells on acute liver failure by enhancing cxcr4 expression |
| url | http://dx.doi.org/10.1155/2020/1498315 |
| work_keys_str_mv | AT henie il1bpretreatmentimprovestheefficacyofmesenchymalstemcellsonacuteliverfailurebyenhancingcxcr4expression AT fangmeian il1bpretreatmentimprovestheefficacyofmesenchymalstemcellsonacuteliverfailurebyenhancingcxcr4expression AT jiemei il1bpretreatmentimprovestheefficacyofmesenchymalstemcellsonacuteliverfailurebyenhancingcxcr4expression AT chengyang il1bpretreatmentimprovestheefficacyofmesenchymalstemcellsonacuteliverfailurebyenhancingcxcr4expression AT qiangzhan il1bpretreatmentimprovestheefficacyofmesenchymalstemcellsonacuteliverfailurebyenhancingcxcr4expression AT qinglinzhang il1bpretreatmentimprovestheefficacyofmesenchymalstemcellsonacuteliverfailurebyenhancingcxcr4expression |