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Innovative Medicines & Omics MSC exosomes for digestive tumors: Bench to bedside

Table 4. The role of MSC‑exo in pancreatic cancer
MSC‑exo Loaded small Cell line Animal model Mechanism of action Effect References
molecule
UCMSCs miR-100-5p BxPC-3; PANC-1 PANC-1 cell - Promoted pancreatic [51]
xenograft in BALB/c ductal adenocarcinoma
nude mice growth
UCMSCs miR-145-5p PANC-1; BxPC; BALB/c PANC-1 cell Downregulated Inhibited pancreatic [52]
Capan-1; xenograft in BALB/c the TGF-β/Smad3 cancer progression
CFPAC-1 nude mice pathway
BMMSCs miR‐1231 BxPC‐3; MIA BxPC‐3 cell Downregulated Inhibited pancreatic [53]
PaCa‐2; PANC‐1; xenograft in BALB/c the EGFR/cyclin E cancer cell proliferation
SW1990 nude mice pathway
Abbreviations: BMMSCs: Bone marrow mesenchymal stem cells; UCMSCs: Umbilical cord mesenchymal stem cells; MSC-exo: Mesenchymal stem
cell-derived exosomes.

targeting therapies is crucial for the future management (Tregs), resulting in notable therapeutic outcomes in cancer
of pancreatic cancer. The good tumor-targeting ability and treatment. The findings suggest that MSC-exo can be used
deep tissue penetration capability of MSC-exo make them as drug delivery vehicles to enhance immunogenicity and
ideal carriers for drugs targeting pancreatic cancer. 54-56 regulate the TME, providing a theoretical foundation for
In an effort to address the chemoresistance of pancreatic the advancement of novel pancreatic cancer treatments. 58
cancer, Zhou et al. encapsulated PTX, gemcitabine 3.5. Other malignant tumors of the digestive system
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monophosphate, and an intermediate metabolite of
gemcitabine into purified BMMSC-exo. Their findings MSC-exo has also demonstrated certain potential for the
revealed that the BMMSC-exo-based drug delivery system treatment of esophageal cancer. For example, miR-375
demonstrated excellent targeting and tissue penetration in UCMSC-exo can inhibit the proliferation, invasion,
and migration of esophageal squamous cell carcinoma
capabilities. This approach resulted in a promising cells while promoting apoptosis by suppressing ENAH
anti-tumor effect while minimizing systemic toxicity. expression and regulating the protein levels of Bax and
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Zhou et al. employed BMMSC-exo to simultaneously E-cadherin. Several studies have focused on using MSC-
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deliver galectin-9 siRNA and OXA, effectively reversing exo for treating biliary tract cancer. For example, miR-
the immunosuppressive TME. This was achieved by 15a-5p in UCMSC-Exo can hinder the progression of
suppressing M2 macrophage polarization and promoting cholangiocarcinoma by inhibiting CHEK1 expression.
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the recruitment of cytotoxic T cells, thereby improving the However, the role of MSC-exo in tumor cells remains
efficacy of immunotherapy in treating pancreatic cancer. controversial, likely due to the exosomes’ inherent
OXA is a critical component of the standardized complexity and diversity, as well as variations in culture
FOLFIRINOX regimen for pancreatic cancer, capable conditions.
of triggering immunogenic cell death (ICD) at the
tumor site and killing tumor cells by inhibiting DNA 4. MSC-exo as a vehicle for drug delivery
synthesis and repair. To further enhance the anti-tumor Drugs can be loaded into exosomes through pre-
effect, a research group used galectin-9 siRNA to block loading (before exosome isolation) and post-loading
the galectin-9/dectin-1 interaction, synergizing with (after exosome isolation). Common exogenous drug-
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OXA to reverse M2 tumor-associated macrophage- loading methods include electroporation, co-incubation,
induced immunosuppression. This delivery platform sonication, freeze-thaw cycles, and extrusion. The
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was developed by encapsulating galectin-9 siRNA via primary advantage of post-loading is its simple process.
electroporation and functionalizing the surface with an However, post-loading has certain drawbacks, such as the
OXA prodrug to act as an ICD inducer. In addition, the potential to damage the integrity of exosomes during the
research group engineered siRNA-exosome-OXA (iEXO- loading process. Moreover, some exosomes may fail to load
OXA) nanoparticles and reported that siRNA EXO-OXA the drugs successfully, necessitating additional purification
enhanced the drug concentration at the tumor site. EXO- steps to remove them. Pre-loading involves introducing or
OXA promoted anti-tumor immunity by driving the expressing target molecules (e.g., nucleic acids, proteins,
polarization of tumor-suppressive macrophages, recruiting or drugs) into MSCs before exosome isolation. The target
cytotoxic T lymphocytes, and reducing regulatory T cells molecules are then incorporated into exosomes, which

Volume 2 Issue 3 (2025) 7 doi: 10.36922/IMO025210025