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...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-05-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225006042 |
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| Summary: | 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. |
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| ISSN: | 2589-0042 |