Bioengineer mesenchymal stem cell for treatment of glioma by IL‐12 mediated microenvironment reprogramming and nCD47‐SLAMF7 mediated phagocytosis regulation of macrophages
Abstract High expression of cellular self‐activated immunosuppressive molecules and extensive infiltration of suppressive immune cells in the tumor microenvironment are the main factors contributing to glioma's resistance to immunotherapy. Nonetheless, technology to modify the expression of gli...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-12-01
|
| Series: | Exploration |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/EXP.20240027 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846116375031971840 |
|---|---|
| author | Man Li Lisen Lu Qungen Xiao Ali Abdi Maalim Bin Nie Yanchao Liu Ulf D. Kahlert Kai Shu Ting Lei Mingxin Zhu |
| author_facet | Man Li Lisen Lu Qungen Xiao Ali Abdi Maalim Bin Nie Yanchao Liu Ulf D. Kahlert Kai Shu Ting Lei Mingxin Zhu |
| author_sort | Man Li |
| collection | DOAJ |
| description | Abstract High expression of cellular self‐activated immunosuppressive molecules and extensive infiltration of suppressive immune cells in the tumor microenvironment are the main factors contributing to glioma's resistance to immunotherapy. Nonetheless, technology to modify the expression of glioma cellular self‐molecules through gene editing requires further development. This project advances cell therapy strategies to reverse the immunosuppressive microenvironment of glioma (TIME). Bone marrow‐derived mesenchymal stem cells (MSCs) are engineered to express bioactive proteins and demonstrate tumor‐homing characteristics upon activation by TGF‐β. These MSCs are designed to secrete the anti‐tumor immune cytokine IL‐12 and the nCD47‐SLAMF7 fusion protein, which regulates T‐cell activity and macrophage phagocytosis. The engineered MSCs are then injected in situ into the glioma site, circumventing the blood‐brain barrier to deliver high local concentrations of bioactive proteins. This approach aims to enhance the M1 polarization of infiltrating macrophages, stimulate macrophage‐mediated tumor cell phagocytosis, activate antigen‐presenting cells, and promote effector CD8+ T cell infiltration, effectively controlling glioma. Additionally, the engineered MSCs may serve as a universal treatment for other tumors that express TGF‐β at high levels. This study proposes a novel treatment strategy for the clinical management of glioma patients. |
| format | Article |
| id | doaj-art-1be42c1c24a94f7eb600bd0091a6ba0c |
| institution | Kabale University |
| issn | 2766-8509 2766-2098 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Exploration |
| spelling | doaj-art-1be42c1c24a94f7eb600bd0091a6ba0c2024-12-19T04:18:00ZengWileyExploration2766-85092766-20982024-12-0146n/an/a10.1002/EXP.20240027Bioengineer mesenchymal stem cell for treatment of glioma by IL‐12 mediated microenvironment reprogramming and nCD47‐SLAMF7 mediated phagocytosis regulation of macrophagesMan Li0Lisen Lu1Qungen Xiao2Ali Abdi Maalim3Bin Nie4Yanchao Liu5Ulf D. Kahlert6Kai Shu7Ting Lei8Mingxin Zhu9Department of Anesthesiology and Pain Medicine Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health and Wuhan Clinical Research Center for Geriatric Anesthesia Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan People's Republic of ChinaCollege of Biomedicine and Health and College of Life Science and Technology Huazhong Agricultural University Wuhan ChinaDepartment of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan People's Republic of ChinaDepartment of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan People's Republic of ChinaDepartment of Anesthesiology and Pain Medicine Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health and Wuhan Clinical Research Center for Geriatric Anesthesia Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan People's Republic of ChinaDepartment of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan People's Republic of ChinaMolecular and Experimental Surgery Clinic for General‐, Visceral‐, Vascular and Transplant Surgery Faculty of Medicine and University Hospital Magdeburg Otto‐von‐Guericke University Magdeburg GermanyDepartment of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan People's Republic of ChinaDepartment of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan People's Republic of ChinaDepartment of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan People's Republic of ChinaAbstract High expression of cellular self‐activated immunosuppressive molecules and extensive infiltration of suppressive immune cells in the tumor microenvironment are the main factors contributing to glioma's resistance to immunotherapy. Nonetheless, technology to modify the expression of glioma cellular self‐molecules through gene editing requires further development. This project advances cell therapy strategies to reverse the immunosuppressive microenvironment of glioma (TIME). Bone marrow‐derived mesenchymal stem cells (MSCs) are engineered to express bioactive proteins and demonstrate tumor‐homing characteristics upon activation by TGF‐β. These MSCs are designed to secrete the anti‐tumor immune cytokine IL‐12 and the nCD47‐SLAMF7 fusion protein, which regulates T‐cell activity and macrophage phagocytosis. The engineered MSCs are then injected in situ into the glioma site, circumventing the blood‐brain barrier to deliver high local concentrations of bioactive proteins. This approach aims to enhance the M1 polarization of infiltrating macrophages, stimulate macrophage‐mediated tumor cell phagocytosis, activate antigen‐presenting cells, and promote effector CD8+ T cell infiltration, effectively controlling glioma. Additionally, the engineered MSCs may serve as a universal treatment for other tumors that express TGF‐β at high levels. This study proposes a novel treatment strategy for the clinical management of glioma patients.https://doi.org/10.1002/EXP.20240027CD47‐SLAMF7gliomamesenchymal stem cells |
| spellingShingle | Man Li Lisen Lu Qungen Xiao Ali Abdi Maalim Bin Nie Yanchao Liu Ulf D. Kahlert Kai Shu Ting Lei Mingxin Zhu Bioengineer mesenchymal stem cell for treatment of glioma by IL‐12 mediated microenvironment reprogramming and nCD47‐SLAMF7 mediated phagocytosis regulation of macrophages Exploration CD47‐SLAMF7 glioma mesenchymal stem cells |
| title | Bioengineer mesenchymal stem cell for treatment of glioma by IL‐12 mediated microenvironment reprogramming and nCD47‐SLAMF7 mediated phagocytosis regulation of macrophages |
| title_full | Bioengineer mesenchymal stem cell for treatment of glioma by IL‐12 mediated microenvironment reprogramming and nCD47‐SLAMF7 mediated phagocytosis regulation of macrophages |
| title_fullStr | Bioengineer mesenchymal stem cell for treatment of glioma by IL‐12 mediated microenvironment reprogramming and nCD47‐SLAMF7 mediated phagocytosis regulation of macrophages |
| title_full_unstemmed | Bioengineer mesenchymal stem cell for treatment of glioma by IL‐12 mediated microenvironment reprogramming and nCD47‐SLAMF7 mediated phagocytosis regulation of macrophages |
| title_short | Bioengineer mesenchymal stem cell for treatment of glioma by IL‐12 mediated microenvironment reprogramming and nCD47‐SLAMF7 mediated phagocytosis regulation of macrophages |
| title_sort | bioengineer mesenchymal stem cell for treatment of glioma by il 12 mediated microenvironment reprogramming and ncd47 slamf7 mediated phagocytosis regulation of macrophages |
| topic | CD47‐SLAMF7 glioma mesenchymal stem cells |
| url | https://doi.org/10.1002/EXP.20240027 |
| work_keys_str_mv | AT manli bioengineermesenchymalstemcellfortreatmentofgliomabyil12mediatedmicroenvironmentreprogrammingandncd47slamf7mediatedphagocytosisregulationofmacrophages AT lisenlu bioengineermesenchymalstemcellfortreatmentofgliomabyil12mediatedmicroenvironmentreprogrammingandncd47slamf7mediatedphagocytosisregulationofmacrophages AT qungenxiao bioengineermesenchymalstemcellfortreatmentofgliomabyil12mediatedmicroenvironmentreprogrammingandncd47slamf7mediatedphagocytosisregulationofmacrophages AT aliabdimaalim bioengineermesenchymalstemcellfortreatmentofgliomabyil12mediatedmicroenvironmentreprogrammingandncd47slamf7mediatedphagocytosisregulationofmacrophages AT binnie bioengineermesenchymalstemcellfortreatmentofgliomabyil12mediatedmicroenvironmentreprogrammingandncd47slamf7mediatedphagocytosisregulationofmacrophages AT yanchaoliu bioengineermesenchymalstemcellfortreatmentofgliomabyil12mediatedmicroenvironmentreprogrammingandncd47slamf7mediatedphagocytosisregulationofmacrophages AT ulfdkahlert bioengineermesenchymalstemcellfortreatmentofgliomabyil12mediatedmicroenvironmentreprogrammingandncd47slamf7mediatedphagocytosisregulationofmacrophages AT kaishu bioengineermesenchymalstemcellfortreatmentofgliomabyil12mediatedmicroenvironmentreprogrammingandncd47slamf7mediatedphagocytosisregulationofmacrophages AT tinglei bioengineermesenchymalstemcellfortreatmentofgliomabyil12mediatedmicroenvironmentreprogrammingandncd47slamf7mediatedphagocytosisregulationofmacrophages AT mingxinzhu bioengineermesenchymalstemcellfortreatmentofgliomabyil12mediatedmicroenvironmentreprogrammingandncd47slamf7mediatedphagocytosisregulationofmacrophages |