Lung delivery of MSCs expressing anti-cancer protein TRAIL visualised with 89Zr-oxine PET-CT
Abstract Background MSCTRAIL is a cell-based therapy consisting of human allogeneic umbilical cord-derived MSCs genetically modified to express the anti-cancer protein TRAIL. Though cell-based therapies are typically designed with a target tissue in mind, delivery is rarely assessed due to a lack of...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-06-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-020-01770-z |
| _version_ | 1818294323198820352 |
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| author | P. Stephen Patrick Krishna K. Kolluri May Zaw Thin Adam Edwards Elizabeth K. Sage Tom Sanderson Benjamin D. Weil John C. Dickson Mark F. Lythgoe Mark Lowdell Sam M. Janes Tammy L. Kalber |
| author_facet | P. Stephen Patrick Krishna K. Kolluri May Zaw Thin Adam Edwards Elizabeth K. Sage Tom Sanderson Benjamin D. Weil John C. Dickson Mark F. Lythgoe Mark Lowdell Sam M. Janes Tammy L. Kalber |
| author_sort | P. Stephen Patrick |
| collection | DOAJ |
| description | Abstract Background MSCTRAIL is a cell-based therapy consisting of human allogeneic umbilical cord-derived MSCs genetically modified to express the anti-cancer protein TRAIL. Though cell-based therapies are typically designed with a target tissue in mind, delivery is rarely assessed due to a lack of translatable non-invasive imaging approaches. In this preclinical study, we demonstrate 89Zr-oxine labelling and PET-CT imaging as a potential clinical solution for non-invasively tracking MSCTRAIL biodistribution. Future implementation of this technique should improve our understanding of MSCTRAIL during its evaluation as a therapy for metastatic lung adenocarcinoma. Methods MSCTRAIL were radiolabelled with 89Zr-oxine and assayed for viability, phenotype, and therapeutic efficacy post-labelling. PET-CT imaging of 89Zr-oxine-labelled MSCTRAIL was performed in a mouse model of lung cancer following intravenous injection, and biodistribution was confirmed ex vivo. Results MSCTRAIL retained the therapeutic efficacy and MSC phenotype in vitro at labelling amounts up to and above those required for clinical imaging. The effect of 89Zr-oxine labelling on cell proliferation rate was amount- and time-dependent. PET-CT imaging showed delivery of MSCTRAIL to the lungs in a mouse model of lung cancer up to 1 week post-injection, validated by in vivo bioluminescence imaging, autoradiography, and fluorescence imaging on tissue sections. Conclusions 89Zr-oxine labelling and PET-CT imaging present a potential method of evaluating the biodistribution of new cell therapies in patients, including MSCTRAIL. This offers to improve understanding of cell therapies, including mechanism of action, migration dynamics, and inter-patient variability. |
| first_indexed | 2024-12-13T03:29:55Z |
| format | Article |
| id | doaj.art-77b713e5b32c4ca89d12cd9d999e858f |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-13T03:29:55Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-77b713e5b32c4ca89d12cd9d999e858f2022-12-22T00:01:11ZengBMCStem Cell Research & Therapy1757-65122020-06-0111111210.1186/s13287-020-01770-zLung delivery of MSCs expressing anti-cancer protein TRAIL visualised with 89Zr-oxine PET-CTP. Stephen Patrick0Krishna K. Kolluri1May Zaw Thin2Adam Edwards3Elizabeth K. Sage4Tom Sanderson5Benjamin D. Weil6John C. Dickson7Mark F. Lythgoe8Mark Lowdell9Sam M. Janes10Tammy L. Kalber11Centre for Advanced Biomedical Imaging, Division of Medicine, University College LondonLungs for Living Research Centre, UCL Respiratory, Division of Medicine, University College LondonCentre for Advanced Biomedical Imaging, Division of Medicine, University College LondonLungs for Living Research Centre, UCL Respiratory, Division of Medicine, University College LondonLungs for Living Research Centre, UCL Respiratory, Division of Medicine, University College LondonInstitute of Nuclear Medicine, University College LondonCentre for Cell, Gene & Tissue Therapeutics, Royal Free HospitalInstitute of Nuclear Medicine, University College LondonCentre for Advanced Biomedical Imaging, Division of Medicine, University College LondonCentre for Cell, Gene & Tissue Therapeutics, Royal Free HospitalLungs for Living Research Centre, UCL Respiratory, Division of Medicine, University College LondonCentre for Advanced Biomedical Imaging, Division of Medicine, University College LondonAbstract Background MSCTRAIL is a cell-based therapy consisting of human allogeneic umbilical cord-derived MSCs genetically modified to express the anti-cancer protein TRAIL. Though cell-based therapies are typically designed with a target tissue in mind, delivery is rarely assessed due to a lack of translatable non-invasive imaging approaches. In this preclinical study, we demonstrate 89Zr-oxine labelling and PET-CT imaging as a potential clinical solution for non-invasively tracking MSCTRAIL biodistribution. Future implementation of this technique should improve our understanding of MSCTRAIL during its evaluation as a therapy for metastatic lung adenocarcinoma. Methods MSCTRAIL were radiolabelled with 89Zr-oxine and assayed for viability, phenotype, and therapeutic efficacy post-labelling. PET-CT imaging of 89Zr-oxine-labelled MSCTRAIL was performed in a mouse model of lung cancer following intravenous injection, and biodistribution was confirmed ex vivo. Results MSCTRAIL retained the therapeutic efficacy and MSC phenotype in vitro at labelling amounts up to and above those required for clinical imaging. The effect of 89Zr-oxine labelling on cell proliferation rate was amount- and time-dependent. PET-CT imaging showed delivery of MSCTRAIL to the lungs in a mouse model of lung cancer up to 1 week post-injection, validated by in vivo bioluminescence imaging, autoradiography, and fluorescence imaging on tissue sections. Conclusions 89Zr-oxine labelling and PET-CT imaging present a potential method of evaluating the biodistribution of new cell therapies in patients, including MSCTRAIL. This offers to improve understanding of cell therapies, including mechanism of action, migration dynamics, and inter-patient variability.http://link.springer.com/article/10.1186/s13287-020-01770-zPET-CTCell trackingTRAIL89Zr-oxineCord-derived MSCsCell therapy |
| spellingShingle | P. Stephen Patrick Krishna K. Kolluri May Zaw Thin Adam Edwards Elizabeth K. Sage Tom Sanderson Benjamin D. Weil John C. Dickson Mark F. Lythgoe Mark Lowdell Sam M. Janes Tammy L. Kalber Lung delivery of MSCs expressing anti-cancer protein TRAIL visualised with 89Zr-oxine PET-CT Stem Cell Research & Therapy PET-CT Cell tracking TRAIL 89Zr-oxine Cord-derived MSCs Cell therapy |
| title | Lung delivery of MSCs expressing anti-cancer protein TRAIL visualised with 89Zr-oxine PET-CT |
| title_full | Lung delivery of MSCs expressing anti-cancer protein TRAIL visualised with 89Zr-oxine PET-CT |
| title_fullStr | Lung delivery of MSCs expressing anti-cancer protein TRAIL visualised with 89Zr-oxine PET-CT |
| title_full_unstemmed | Lung delivery of MSCs expressing anti-cancer protein TRAIL visualised with 89Zr-oxine PET-CT |
| title_short | Lung delivery of MSCs expressing anti-cancer protein TRAIL visualised with 89Zr-oxine PET-CT |
| title_sort | lung delivery of mscs expressing anti cancer protein trail visualised with 89zr oxine pet ct |
| topic | PET-CT Cell tracking TRAIL 89Zr-oxine Cord-derived MSCs Cell therapy |
| url | http://link.springer.com/article/10.1186/s13287-020-01770-z |
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