Evaluating the potential of off-the-shelf engineered mesenchymal stem cells for targeted Hepatocellular Carcinoma treatment: A multisite proof-of-concept study.

Although combining 5-fluorouracil (5-FU) and Interferon-beta (IFNb) improves response rates in Hepatocellular Carcinoma (HCC), the outcomes remain suboptimal. This study investigates the feasibility of using highly transfected Mesenchymal Stem Cells (MSCs) to deliver a chemotherapeutic (5-FU) and an immunomodulator (IFNb) for localized HCC treatment. Considering the crucial role of cold-chain transportation in off-the-shelf allogeneic therapy, the study also assesses the quality and efficacy of frozen-thawed engineered MSCs, simulating a multisite study process. The engineered MSCs maintained their phenotypes and tumour tropism. With just 10 % engineered MSCs, a killing efficiency of over 70 % was achieved in Huh-7 and HepG2 cell lines in vitro. Coculture studies, soft agar assays, and in vivo experiments confirmed that MSCs are neither tumorigenic nor tumour-promoting. Tumour mass growth was inhibited by >80 % in the treated mice group. TUNEL, Annexin-V, and Ki67 staining confirmed DNA damage, cell death, and proliferation inhibition post-treatment. Blood chemistry and the weight of the mice were comparable to the control group, indicating a good safety profile. This proof-of-concept study demonstrates the efficacy and safety of off-the-shelf CDUPRT-IFNβ_MSCs in targeting hepatocellular carcinoma (HCC) growth. Evaluating the complete value chain of MSC therapy in early-stage preclinical studies is essential for justifying further investigation and clinical translation of this cell product.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper
(Copyright © 2024. Published by Elsevier Masson SAS.)