NKG2D-CAR-targeted iPSC-derived MSCs efficiently target solid tumors expressing NKG2D ligand
Summary: Mesenchymal stem cells (MSCs) hold potential in cancer therapy; however, insufficient tumor homing ability and heterogeneity limit their therapeutic benefits. Obviously, the homogeneous induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) with enhanced ability of tumo...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-05-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225006042 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850197285898551296 |
|---|---|
| author | Shuqing Tang Yusang Zhang Peiyun Wang Qiyu Tang Yating Liu Fan Lu Mengting Han Miaojin Zhou Qian Hu Mai Feng Desheng Liang |
| author_facet | Shuqing Tang Yusang Zhang Peiyun Wang Qiyu Tang Yating Liu Fan Lu Mengting Han Miaojin Zhou Qian Hu Mai Feng Desheng Liang |
| author_sort | Shuqing Tang |
| collection | DOAJ |
| description | Summary: Mesenchymal stem cells (MSCs) hold potential in cancer therapy; however, insufficient tumor homing ability and heterogeneity limit their therapeutic benefits. Obviously, the homogeneous induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) with enhanced ability of tumor targeting could be the solution. In this study, a CAR containing the NKG2D extracellular domain was targeted at the B2M locus of iPSCs to generate NKG2D-CAR-iPSCs, which were subsequently differentiated into NKG2D-CAR-iMSCs. In vitro, NKG2D-CAR significantly enhanced migration and adhesion of iMSCs to a variety of solid tumor cells expressing NKG2D ligands. RNA sequencing (RNA-seq) revealed significant upregulation of genes related to cell adhesion, migration, and binding in NKG2D-CAR-iMSCs. In A549 xenograft model, NKG2D-CAR-iMSCs demonstrated a 57% improvement in tumor-homing ability compared with iMSCs. In conclusion, our findings demonstrate enhanced targeting specificity of NKG2D-CAR-iMSCs to tumor cells expressing NKG2D ligands in vitro and in vivo, facilitating future investigation of iMSCs as an off-the-shelf living carrier for targeted delivery of anti-tumor agents. |
| format | Article |
| id | doaj-art-aa394ce764484f4bb0685c8f8a1d06f3 |
| institution | OA Journals |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-aa394ce764484f4bb0685c8f8a1d06f32025-08-20T02:13:12ZengElsevieriScience2589-00422025-05-0128511234310.1016/j.isci.2025.112343NKG2D-CAR-targeted iPSC-derived MSCs efficiently target solid tumors expressing NKG2D ligandShuqing Tang0Yusang Zhang1Peiyun Wang2Qiyu Tang3Yating Liu4Fan Lu5Mengting Han6Miaojin Zhou7Qian Hu8Mai Feng9Desheng Liang10Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410078, ChinaCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410078, ChinaCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410078, ChinaCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410078, ChinaCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410078, ChinaCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410078, ChinaCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410078, ChinaCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410078, ChinaCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410078, ChinaHunan Key Laboratory of Animal Models for Human Diseases, School of Life Sciences, Central South University, Changsha 410078, ChinaCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410078, China; Corresponding authorSummary: Mesenchymal stem cells (MSCs) hold potential in cancer therapy; however, insufficient tumor homing ability and heterogeneity limit their therapeutic benefits. Obviously, the homogeneous induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) with enhanced ability of tumor targeting could be the solution. In this study, a CAR containing the NKG2D extracellular domain was targeted at the B2M locus of iPSCs to generate NKG2D-CAR-iPSCs, which were subsequently differentiated into NKG2D-CAR-iMSCs. In vitro, NKG2D-CAR significantly enhanced migration and adhesion of iMSCs to a variety of solid tumor cells expressing NKG2D ligands. RNA sequencing (RNA-seq) revealed significant upregulation of genes related to cell adhesion, migration, and binding in NKG2D-CAR-iMSCs. In A549 xenograft model, NKG2D-CAR-iMSCs demonstrated a 57% improvement in tumor-homing ability compared with iMSCs. In conclusion, our findings demonstrate enhanced targeting specificity of NKG2D-CAR-iMSCs to tumor cells expressing NKG2D ligands in vitro and in vivo, facilitating future investigation of iMSCs as an off-the-shelf living carrier for targeted delivery of anti-tumor agents.http://www.sciencedirect.com/science/article/pii/S2589004225006042Natural sciencesBiological sciencesMolecular biologyCell biologySystems biologyCancer systems biology |
| spellingShingle | Shuqing Tang Yusang Zhang Peiyun Wang Qiyu Tang Yating Liu Fan Lu Mengting Han Miaojin Zhou Qian Hu Mai Feng Desheng Liang NKG2D-CAR-targeted iPSC-derived MSCs efficiently target solid tumors expressing NKG2D ligand iScience Natural sciences Biological sciences Molecular biology Cell biology Systems biology Cancer systems biology |
| title | NKG2D-CAR-targeted iPSC-derived MSCs efficiently target solid tumors expressing NKG2D ligand |
| title_full | NKG2D-CAR-targeted iPSC-derived MSCs efficiently target solid tumors expressing NKG2D ligand |
| title_fullStr | NKG2D-CAR-targeted iPSC-derived MSCs efficiently target solid tumors expressing NKG2D ligand |
| title_full_unstemmed | NKG2D-CAR-targeted iPSC-derived MSCs efficiently target solid tumors expressing NKG2D ligand |
| title_short | NKG2D-CAR-targeted iPSC-derived MSCs efficiently target solid tumors expressing NKG2D ligand |
| title_sort | nkg2d car targeted ipsc derived mscs efficiently target solid tumors expressing nkg2d ligand |
| topic | Natural sciences Biological sciences Molecular biology Cell biology Systems biology Cancer systems biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225006042 |
| work_keys_str_mv | AT shuqingtang nkg2dcartargetedipscderivedmscsefficientlytargetsolidtumorsexpressingnkg2dligand AT yusangzhang nkg2dcartargetedipscderivedmscsefficientlytargetsolidtumorsexpressingnkg2dligand AT peiyunwang nkg2dcartargetedipscderivedmscsefficientlytargetsolidtumorsexpressingnkg2dligand AT qiyutang nkg2dcartargetedipscderivedmscsefficientlytargetsolidtumorsexpressingnkg2dligand AT yatingliu nkg2dcartargetedipscderivedmscsefficientlytargetsolidtumorsexpressingnkg2dligand AT fanlu nkg2dcartargetedipscderivedmscsefficientlytargetsolidtumorsexpressingnkg2dligand AT mengtinghan nkg2dcartargetedipscderivedmscsefficientlytargetsolidtumorsexpressingnkg2dligand AT miaojinzhou nkg2dcartargetedipscderivedmscsefficientlytargetsolidtumorsexpressingnkg2dligand AT qianhu nkg2dcartargetedipscderivedmscsefficientlytargetsolidtumorsexpressingnkg2dligand AT maifeng nkg2dcartargetedipscderivedmscsefficientlytargetsolidtumorsexpressingnkg2dligand AT deshengliang nkg2dcartargetedipscderivedmscsefficientlytargetsolidtumorsexpressingnkg2dligand |