Rearming mesenchymal stem cells with engineering strategies to combat cancer.

Area of Science:

• Oncology
• Cell Biology
• Biotechnology

Background:

• Mesenchymal stromal/stem cells (MSCs) are explored as tumor-targeted delivery systems due to their homing abilities.
• However, MSCs can also promote tumor progression via angiogenesis, immune suppression, and therapy resistance within the tumor microenvironment.

Purpose of the Study:

• To review the molecular mechanisms of MSC recruitment by tumors (e.g., CXCL12/CXCR4 axis).
• To explore strategies for engineering MSCs into programmable anticancer therapeutic delivery systems.
• To discuss challenges and future directions for MSC-based antitumor therapies.

Main Methods:

• Review of literature on MSC-tumor interactions and engineering strategies.
• Analysis of molecular pathways involved in MSC recruitment and tumor progression.
• Integration of data on various anticancer payloads delivered by engineered MSCs.

Main Results:

• Tumors exploit a molecular "homing hierarchy," notably the CXCL12/CXCR4 axis, to recruit MSCs.
• Engineered MSCs can function as intratumoral factories delivering suicide genes, apoptotic/anti-angiogenic agents, cytokines, checkpoint inhibitors, and oncolytic viruses.
• Antigen-directed strategies and controlled release mechanisms enhance delivery efficacy and minimize off-target effects.

Conclusions:

• Engineering MSCs to deliver anticancer payloads represents a viable strategy to "turn enemies into allies" in cancer therapy.
• Advanced genetic engineering and combination therapies are crucial for optimizing MSC-based antitumor strategies and enhancing clinical efficacy.
• Overcoming challenges in harnessing MSCs is key to realizing their full therapeutic potential.