Engineered Mesenchymal Stromal Cells in Oncology: Navigating Between Therapeutic Delivery and Tumor Promotion

TL;DR

This review explores how engineered mesenchymal stromal cells can both deliver cancer therapies and potentially promote tumor growth, highlighting the need for balanced strategies.

Contribution

The paper provides a balanced overview of the dual role of engineered MSCs in oncology, emphasizing both therapeutic potential and risks.

Findings

Engineered MSCs can deliver therapies directly to tumors, improving targeting and reducing toxicity.

MSCs can promote tumor growth by altering the tumor microenvironment and enhancing metastasis.

MSC-derived extracellular vesicles offer a cell-free alternative for targeted drug delivery.

Abstract

Mesenchymal stromal cells (MSCs) are intensively investigated in oncology owing to their intrinsic tumor-homing ability and capacity to deliver therapeutic agents directly into the tumor microenvironment (TME). Recent advances in genetic engineering have enabled precise modification of MSCs, allowing controlled expression of therapeutic genes and other cargo delivery, thus improving targeting efficiency. As cellular carriers, MSCs have been engineered to transport oncolytic viruses, suicide genes in gene-directed enzyme prodrug therapy (GDEPT), multifunctional nanoparticles, and therapeutic factors such as IFN-β or TRAIL, while engineered MSC-derived extracellular vesicles (MSC-EVs) offer a promising cell-free alternative. These strategies increase intratumoral drug concentration, amplify bystander effects, and synergize with standard therapies while reducing systemic toxicity. Conversely, accumulating evidence highlights the tumor-promoting properties of MSCs: once recruited by inflammatory and hypoxic cues, they remodel the tumor microenvironment by stimulating angiogenesis, suppressing immune responses, differentiating into cancer-associated fibroblasts, and promoting epithelial-to-mesenchymal transition (EMT), ultimately enhancing invasion, metastasis, and therapy resistance. This duality has sparked both enthusiasm and concern in the oncology field. The present review outlines the paradoxical role of MSCs in oncology—ranging from their potential to promote tumor growth to their emerging utility as vehicles for targeted drug delivery. By highlighting both therapeutic opportunities and biological risks, we aim to provide a balanced perspective on how MSC-based strategies might be refined, optimized, and safely integrated into future cancer therapies.

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