Human amniotic mesenchymal stem cells and their paracrine factors promote wound healing by inhibiting heat stress-induced skin cell apoptosis and enhancing their proliferation through activating PI3K/AKT signaling pathway
Abstract Background Increasing evidence has shown that mesenchymal stem cells (MSCs) yield a favorable therapeutic benefit for thermal burn skin wounds. Human amniotic MSCs (hAMSCs) derived from amniotic membrane have multilineage differentiation, immunosuppressive, and anti-inflammatory potential w...
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| Format: | Article |
| Language: | English |
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BMC
2019-08-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-019-1366-y |
| _version_ | 1818282886789332992 |
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| author | Jing-Yuan Li Kang-Kang Ren Wen-Jie Zhang Ling Xiao Han-You Wu Qian-Yu Liu Ting Ding Xiang-Cheng Zhang Wen-Jia Nie Yu Ke Ke-Yu Deng Quan-Wen Liu Hong-Bo Xin |
| author_facet | Jing-Yuan Li Kang-Kang Ren Wen-Jie Zhang Ling Xiao Han-You Wu Qian-Yu Liu Ting Ding Xiang-Cheng Zhang Wen-Jia Nie Yu Ke Ke-Yu Deng Quan-Wen Liu Hong-Bo Xin |
| author_sort | Jing-Yuan Li |
| collection | DOAJ |
| description | Abstract Background Increasing evidence has shown that mesenchymal stem cells (MSCs) yield a favorable therapeutic benefit for thermal burn skin wounds. Human amniotic MSCs (hAMSCs) derived from amniotic membrane have multilineage differentiation, immunosuppressive, and anti-inflammatory potential which makes them suitable for treating skin wounds. However, the exact effects of hAMSCs on the healing of thermal burn skin wounds and their potential mechanisms are not explored. Methods hAMSCs were isolated from amniotic membrane and characterized by RT-PCR, flow cytometry, immunofluorescence, and tumorigenicity test. We assessed the effects of hAMSCs and hAMSC conditional medium (CM) on wound healing in a deep second-degree burn injury model of mice. We then investigated the biological effects of hAMSCs and hAMSC-CM on the apoptosis and proliferation of heat stress-injured human keratinocytes HaCAT and dermal fibroblasts (DFL) both in vivo and in vitro. Next, we explored the underlying mechanisms by assessing PI3K/AKT and GSK3β/β-catenin signaling pathways in heat injured HaCAT and DFL cells after hAMSCs and hAMSC-CM treatments using PI3K inhibitor LY294002 and β-catenin inhibitor ICG001. Antibody array assay was used to identify the cytokines secreted by hAMSCs that may activate PI3K/AKT signaling pathway. Results Our results showed that hAMSCs expressed various markers of embryonic stem cells and mesenchymal stem cells and have low immunogenicity and no tumorigenicity. hAMSC and hAMSC-CM transplantation significantly promoted thermal burn wound healing by accelerating re-epithelialization with increased expression of CK19 and PCNA in vivo. hAMSCs and hAMSC-CM markedly inhibited heat stress-induced apoptosis in HaCAT and DFL cells in vitro through activation of PI3K/AKT signaling and promoted their proliferation by activating GSK3β/β-catenin signaling. Furthermore, we demonstrated that hAMSC-mediated activation of GSK3β/β-catenin signaling was dependent on PI3K/AKT signaling pathway. Antibody array assay showed that a panel of cytokines including PAI-1, C-GSF, periostin, and TIMP-1 delivered from hAMSCs may contribute to the improvement of the wound healing through activating PI3K/AKT signaling pathway. Conclusion Our results demonstrated that hAMSCs and hAMSC-CM efficiently cure heat stress-induced skin injury by inhibiting apoptosis of skin cells and promoting their proliferation through activating PI3K/AKT signaling pathway, suggesting that hAMSCs and hAMSC-CM may provide an alternative therapeutic approach for the treatment of skin injury. |
| first_indexed | 2024-12-13T00:28:09Z |
| format | Article |
| id | doaj.art-87b54e7beab24e0196fd51c417ff39b0 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-13T00:28:09Z |
| publishDate | 2019-08-01 |
| publisher | BMC |
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| series | Stem Cell Research & Therapy |
| spelling | doaj.art-87b54e7beab24e0196fd51c417ff39b02022-12-22T00:05:23ZengBMCStem Cell Research & Therapy1757-65122019-08-0110111710.1186/s13287-019-1366-yHuman amniotic mesenchymal stem cells and their paracrine factors promote wound healing by inhibiting heat stress-induced skin cell apoptosis and enhancing their proliferation through activating PI3K/AKT signaling pathwayJing-Yuan Li0Kang-Kang Ren1Wen-Jie Zhang2Ling Xiao3Han-You Wu4Qian-Yu Liu5Ting Ding6Xiang-Cheng Zhang7Wen-Jia Nie8Yu Ke9Ke-Yu Deng10Quan-Wen Liu11Hong-Bo Xin12The National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang UniversityThe National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang UniversityThe National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang UniversityThe National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang UniversityThe National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang UniversityThe National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang UniversityThe National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang UniversityDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang UniversityThe National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang UniversityThe National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang UniversityThe National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang UniversityThe National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang UniversityThe National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang UniversityAbstract Background Increasing evidence has shown that mesenchymal stem cells (MSCs) yield a favorable therapeutic benefit for thermal burn skin wounds. Human amniotic MSCs (hAMSCs) derived from amniotic membrane have multilineage differentiation, immunosuppressive, and anti-inflammatory potential which makes them suitable for treating skin wounds. However, the exact effects of hAMSCs on the healing of thermal burn skin wounds and their potential mechanisms are not explored. Methods hAMSCs were isolated from amniotic membrane and characterized by RT-PCR, flow cytometry, immunofluorescence, and tumorigenicity test. We assessed the effects of hAMSCs and hAMSC conditional medium (CM) on wound healing in a deep second-degree burn injury model of mice. We then investigated the biological effects of hAMSCs and hAMSC-CM on the apoptosis and proliferation of heat stress-injured human keratinocytes HaCAT and dermal fibroblasts (DFL) both in vivo and in vitro. Next, we explored the underlying mechanisms by assessing PI3K/AKT and GSK3β/β-catenin signaling pathways in heat injured HaCAT and DFL cells after hAMSCs and hAMSC-CM treatments using PI3K inhibitor LY294002 and β-catenin inhibitor ICG001. Antibody array assay was used to identify the cytokines secreted by hAMSCs that may activate PI3K/AKT signaling pathway. Results Our results showed that hAMSCs expressed various markers of embryonic stem cells and mesenchymal stem cells and have low immunogenicity and no tumorigenicity. hAMSC and hAMSC-CM transplantation significantly promoted thermal burn wound healing by accelerating re-epithelialization with increased expression of CK19 and PCNA in vivo. hAMSCs and hAMSC-CM markedly inhibited heat stress-induced apoptosis in HaCAT and DFL cells in vitro through activation of PI3K/AKT signaling and promoted their proliferation by activating GSK3β/β-catenin signaling. Furthermore, we demonstrated that hAMSC-mediated activation of GSK3β/β-catenin signaling was dependent on PI3K/AKT signaling pathway. Antibody array assay showed that a panel of cytokines including PAI-1, C-GSF, periostin, and TIMP-1 delivered from hAMSCs may contribute to the improvement of the wound healing through activating PI3K/AKT signaling pathway. Conclusion Our results demonstrated that hAMSCs and hAMSC-CM efficiently cure heat stress-induced skin injury by inhibiting apoptosis of skin cells and promoting their proliferation through activating PI3K/AKT signaling pathway, suggesting that hAMSCs and hAMSC-CM may provide an alternative therapeutic approach for the treatment of skin injury.http://link.springer.com/article/10.1186/s13287-019-1366-yHuman amniotic membrane mesenchymal stem cellsConditioned mediumWound healingPI3K/AKT signalingAntibody array |
| spellingShingle | Jing-Yuan Li Kang-Kang Ren Wen-Jie Zhang Ling Xiao Han-You Wu Qian-Yu Liu Ting Ding Xiang-Cheng Zhang Wen-Jia Nie Yu Ke Ke-Yu Deng Quan-Wen Liu Hong-Bo Xin Human amniotic mesenchymal stem cells and their paracrine factors promote wound healing by inhibiting heat stress-induced skin cell apoptosis and enhancing their proliferation through activating PI3K/AKT signaling pathway Stem Cell Research & Therapy Human amniotic membrane mesenchymal stem cells Conditioned medium Wound healing PI3K/AKT signaling Antibody array |
| title | Human amniotic mesenchymal stem cells and their paracrine factors promote wound healing by inhibiting heat stress-induced skin cell apoptosis and enhancing their proliferation through activating PI3K/AKT signaling pathway |
| title_full | Human amniotic mesenchymal stem cells and their paracrine factors promote wound healing by inhibiting heat stress-induced skin cell apoptosis and enhancing their proliferation through activating PI3K/AKT signaling pathway |
| title_fullStr | Human amniotic mesenchymal stem cells and their paracrine factors promote wound healing by inhibiting heat stress-induced skin cell apoptosis and enhancing their proliferation through activating PI3K/AKT signaling pathway |
| title_full_unstemmed | Human amniotic mesenchymal stem cells and their paracrine factors promote wound healing by inhibiting heat stress-induced skin cell apoptosis and enhancing their proliferation through activating PI3K/AKT signaling pathway |
| title_short | Human amniotic mesenchymal stem cells and their paracrine factors promote wound healing by inhibiting heat stress-induced skin cell apoptosis and enhancing their proliferation through activating PI3K/AKT signaling pathway |
| title_sort | human amniotic mesenchymal stem cells and their paracrine factors promote wound healing by inhibiting heat stress induced skin cell apoptosis and enhancing their proliferation through activating pi3k akt signaling pathway |
| topic | Human amniotic membrane mesenchymal stem cells Conditioned medium Wound healing PI3K/AKT signaling Antibody array |
| url | http://link.springer.com/article/10.1186/s13287-019-1366-y |
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