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Cryopreservation of human mesenchymal stromal cells expressing TRAIL for human anti-cancer therapy

Yuan, Z; Lourenco, SDS; Sage, EK; Kolluri, KK; Lowdell, MW; Janes, SM; (2016) Cryopreservation of human mesenchymal stromal cells expressing TRAIL for human anti-cancer therapy. Cytotherapy , 18 (7) pp. 860-869. 10.1016/j.jcyt.2016.04.005. Green open access

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Abstract

Background aims Mesenchymal stromal cells (MSCs) are being extensively researched for cell therapy and tissue engineering. We have engineered MSCs to express the pro-apoptotic protein tumor necrosis factor–related apoptosis inducing ligand (TRAIL) and are currently preparing this genetically modified cell therapy for a phase 1/2a clinical trial in patients with metastatic lung cancer. To do this, we need to prepare a cryopreserved allogeneic MSCTRAIL cell bank for further expansion before patient delivery. The effects of cryopreservation on a genetically modified cell therapy product have not been clearly determined. Methods We tested different concentrations of dimethyl sulfoxide (DMSO) added to the human serum albumin ZENALB 4.5 and measured post-thaw cell viability, proliferation ability and differentiation characteristics. In addition, we examined the homing ability, TRAIL expression and cancer cell–killing capacities of cryopreserved genetically modified MSCs compared with fresh, continually cultured cells. Results We demonstrated that the post-thaw viability of MSCs in 5% DMSO (v/v) with 95% ZENALB 4.5 (v/v) is 85.7 ± 0.4%, which is comparable to that in conventional freezing media. We show that cryopreservation does not affect the long-term expression of TRAIL and that cryopreserved TRAIL-expressing MSCs exhibit similar levels of homing and, importantly, retain their potency in triggering cancer cell death. Conclusions This study shows that cryopreservation is unlikely to affect the therapeutic properties of MSCTRAIL and supports the generation of a cryopreserved master cell bank.

Type: Article
Title: Cryopreservation of human mesenchymal stromal cells expressing TRAIL for human anti-cancer therapy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jcyt.2016.04.005
Publisher version: http://dx.doi.org/10.1016/j.jcyt.2016.04.005
Language: English
Additional information: Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Keywords: Science & Technology, Life Sciences & Biomedicine, Cell & Tissue Engineering, Biotechnology & Applied Microbiology, Cell Biology, Hematology, Medicine, Research & Experimental, Research & Experimental Medicine, apoptosis, chemokine, cryopreservation, DMSO, MSC, ZENALB 4.5, VERSUS-HOST-DISEASE, STEM-CELLS, BONE-MARROW, ISCHEMIC CARDIOMYOPATHY, STEROID-RESISTANT, RANDOMIZED-TRIAL, CANCER-THERAPY, ACUTE GVHD, MIGRATION, INFUSION
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1497528
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