In vivo monitoring of dynamic interaction between neutrophil and human umbilical cord blood-derived mesenchymal stem cell in mouse liver during sepsis
Abstract Background Sepsis is a global inflammatory disease that causes death. It has been reported that mesenchymal stem cell (MSC) treatment can attenuate inflammatory and septic symptoms. In this study, we investigated how interactions between neutrophils and human umbilical cord blood (hUCB)-MSC...
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| Format: | Article |
| Language: | English |
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BMC
2020-02-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-020-1559-4 |
| _version_ | 1829481469505961984 |
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| author | Sung Yong Ahn Yong-Sun Maeng Yu Rim Kim Young Ho Choe Han Sung Hwang Young-Min Hyun |
| author_facet | Sung Yong Ahn Yong-Sun Maeng Yu Rim Kim Young Ho Choe Han Sung Hwang Young-Min Hyun |
| author_sort | Sung Yong Ahn |
| collection | DOAJ |
| description | Abstract Background Sepsis is a global inflammatory disease that causes death. It has been reported that mesenchymal stem cell (MSC) treatment can attenuate inflammatory and septic symptoms. In this study, we investigated how interactions between neutrophils and human umbilical cord blood (hUCB)-MSCs in the liver of septic mice are involved in mitigating sepsis that is mediated by MSCs. Accordingly, we aimed to determine whether hUCB-MSC application could be an appropriate treatment for sepsis. Methods To induce septic condition, lipopolysaccharide (LPS) was intraperitoneally (i.p.) injected into mice 24 h after the intravenous (i.v.) injection of saline or hUCB-MSCs. To determine the effect of hUCB-MSCs on the immune response during sepsis, histologic analysis, immunoassays, and two-photon intravital imaging were performed 6 h post-LPS injection. For the survival study, mice were monitored for 6 days after LPS injection. Results The injection (i.v.) of hUCB-MSCs alleviated the severity of LPS-induced sepsis by increasing IL-10 levels (p < 0.001) and decreasing mortality (p < 0.05) in septic mice. In addition, this significantly reduced the recruitment of neutrophils (p < 0.001) to the liver. In hUCB-MSC-treated condition, we also observed several distinct patterns of dynamic interactions between neutrophils and hUCB-MSCs in the inflamed mouse liver, as well as vigorous interactions between hepatic stellate cells (HSCs or ito cells) and hUCB-MSCs. Interestingly, hUCB-MSCs that originated from humans were not recognized as foreign in the mouse body and consequently did not cause graft rejection. Conclusions These distinct interaction patterns between innate immune cells and hUCB-MSCs demonstrated that hUCB-MSCs have beneficial effects against LPS-induced sepsis through associations with neutrophils. In addition, the immunomodulatory properties of hUCB-MSCs might enable immune evasion in the host. Taken together, our results suggest the prospects of hUCB-MSCs as a therapeutic tool to inhibit inflammation and alleviate pathological immune responses such as sepsis. |
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| format | Article |
| id | doaj.art-481e7f144ab541dd9e54baf71f2528c5 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-14T21:29:13Z |
| publishDate | 2020-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-481e7f144ab541dd9e54baf71f2528c52022-12-21T22:46:43ZengBMCStem Cell Research & Therapy1757-65122020-02-0111111510.1186/s13287-020-1559-4In vivo monitoring of dynamic interaction between neutrophil and human umbilical cord blood-derived mesenchymal stem cell in mouse liver during sepsisSung Yong Ahn0Yong-Sun Maeng1Yu Rim Kim2Young Ho Choe3Han Sung Hwang4Young-Min Hyun5Department of Anatomy, Yonsei University College of MedicineDepartment of Obstetrics and Gynecology, Yonsei University College of MedicineDepartment of Anatomy, Yonsei University College of MedicineDepartment of Anatomy, Yonsei University College of MedicineDepartment of Obstetrics and Gynecology, Research Institute of Medical Science, Konkuk University School of MedicineDepartment of Anatomy, Yonsei University College of MedicineAbstract Background Sepsis is a global inflammatory disease that causes death. It has been reported that mesenchymal stem cell (MSC) treatment can attenuate inflammatory and septic symptoms. In this study, we investigated how interactions between neutrophils and human umbilical cord blood (hUCB)-MSCs in the liver of septic mice are involved in mitigating sepsis that is mediated by MSCs. Accordingly, we aimed to determine whether hUCB-MSC application could be an appropriate treatment for sepsis. Methods To induce septic condition, lipopolysaccharide (LPS) was intraperitoneally (i.p.) injected into mice 24 h after the intravenous (i.v.) injection of saline or hUCB-MSCs. To determine the effect of hUCB-MSCs on the immune response during sepsis, histologic analysis, immunoassays, and two-photon intravital imaging were performed 6 h post-LPS injection. For the survival study, mice were monitored for 6 days after LPS injection. Results The injection (i.v.) of hUCB-MSCs alleviated the severity of LPS-induced sepsis by increasing IL-10 levels (p < 0.001) and decreasing mortality (p < 0.05) in septic mice. In addition, this significantly reduced the recruitment of neutrophils (p < 0.001) to the liver. In hUCB-MSC-treated condition, we also observed several distinct patterns of dynamic interactions between neutrophils and hUCB-MSCs in the inflamed mouse liver, as well as vigorous interactions between hepatic stellate cells (HSCs or ito cells) and hUCB-MSCs. Interestingly, hUCB-MSCs that originated from humans were not recognized as foreign in the mouse body and consequently did not cause graft rejection. Conclusions These distinct interaction patterns between innate immune cells and hUCB-MSCs demonstrated that hUCB-MSCs have beneficial effects against LPS-induced sepsis through associations with neutrophils. In addition, the immunomodulatory properties of hUCB-MSCs might enable immune evasion in the host. Taken together, our results suggest the prospects of hUCB-MSCs as a therapeutic tool to inhibit inflammation and alleviate pathological immune responses such as sepsis.https://doi.org/10.1186/s13287-020-1559-4Two-photon intravital imagingSepsisHuman umbilical cord blood-mesenchymal stem cellsNeutrophilsHepatic stellate cells |
| spellingShingle | Sung Yong Ahn Yong-Sun Maeng Yu Rim Kim Young Ho Choe Han Sung Hwang Young-Min Hyun In vivo monitoring of dynamic interaction between neutrophil and human umbilical cord blood-derived mesenchymal stem cell in mouse liver during sepsis Stem Cell Research & Therapy Two-photon intravital imaging Sepsis Human umbilical cord blood-mesenchymal stem cells Neutrophils Hepatic stellate cells |
| title | In vivo monitoring of dynamic interaction between neutrophil and human umbilical cord blood-derived mesenchymal stem cell in mouse liver during sepsis |
| title_full | In vivo monitoring of dynamic interaction between neutrophil and human umbilical cord blood-derived mesenchymal stem cell in mouse liver during sepsis |
| title_fullStr | In vivo monitoring of dynamic interaction between neutrophil and human umbilical cord blood-derived mesenchymal stem cell in mouse liver during sepsis |
| title_full_unstemmed | In vivo monitoring of dynamic interaction between neutrophil and human umbilical cord blood-derived mesenchymal stem cell in mouse liver during sepsis |
| title_short | In vivo monitoring of dynamic interaction between neutrophil and human umbilical cord blood-derived mesenchymal stem cell in mouse liver during sepsis |
| title_sort | in vivo monitoring of dynamic interaction between neutrophil and human umbilical cord blood derived mesenchymal stem cell in mouse liver during sepsis |
| topic | Two-photon intravital imaging Sepsis Human umbilical cord blood-mesenchymal stem cells Neutrophils Hepatic stellate cells |
| url | https://doi.org/10.1186/s13287-020-1559-4 |
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