In:
Stem Cell Research & Therapy, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2020-12)
Abstract:
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 89 Zr-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 89 Zr-oxine and assayed for viability, phenotype, and therapeutic efficacy post-labelling. PET-CT imaging of 89 Zr-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 89 Zr-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 89 Zr-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.
Type of Medium:
Online Resource
ISSN:
1757-6512
DOI:
10.1186/s13287-020-01770-z
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2020
detail.hit.zdb_id:
2548671-8
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