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

are subsequently collected. The advantage of pre-loading methods provides a viable approach for achieving
is that it preserves the integrity of the exosomes, but the efficient and high-purity exosome production, though
process is complex, time-consuming, and costly. Despite further improvements in isolation efficiency are still
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substantial progress in the anti-tumor research of MSC- required. 70
exo, several key unresolved issues and limitations hinder (iv) Target specificity and reducing off-target toxicity:
the exosomes’ clinical application: Although MSC-exo displays tumor-targeting
(i) Heterogeneity of MSC-exo: The heterogeneity of MSC- properties, the exosomes can still bind to normal
exo can be managed by standardizing the isolation, tissue cells, necessitating the optimization of exosome
purification, storage, and characterization methods. targeting to reduce off-target toxicity. The most
Standardized procedures can maximize uniformity in commonly used method to enhance exosome targeting
exosome size, composition, and contents. In addition, is genetically engineering tumor-specific ligands on
different extracellular vesicle subpopulations derived the exosome membrane. Lamp2b, the transmembrane
from MSCs should be identified for their anti- protein platelet-derived growth factor receptor,
tumor activity, as different isolation and purification members of the tetraspanin superfamily, and lactoferrin
methods can result in MSC-exo with varying contents, can all serve as exosome membrane targeting ligands
characteristics, and biological functions. 64,65 to improve exosome tumor targeting. RGD (Arg-Gly-
(ii) Large-scale production and storage: The large- Asp) peptides, present in various ECMs, are capable of
scale production and storage of MSC-exo present precisely identifying and attaching to integrins present
significant challenges to its translation into clinical on the surfaces of tumor cells, acting as competitive
practice, largely due to the limited availability of inhibitors of RGD peptide-like substances in vivo.
MSCs. Induced iPSCs, generated by reprogramming This can inhibit tumor cell adhesion and migration to
fully differentiated somatic cells through the the ECM, suppress tumor angiogenesis, and induce
introduction of specific transcription factors, offer a tumor cell apoptosis. Research has demonstrated
potential solution. IPSCs possess the ability to self- that intravenous injection of DOX-containing iRGD-
renew indefinitely and can differentiate into any exosomes can effectively penetrate the blood-spinal
cell type, including MSCs. Therefore, iPSC-MSCs cord barrier and deliver DOX to the spinal cord injury
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(iMSCs) could provide an unlimited source of iMSCs site, enhancing neurological function recovery. 71
to overcome the limitations of primary MSCs, making Although generating exosomes from modified MSCs
them a primary source for large-scale applications. offers new possibilities for cancer treatment, it also carries
Studies have compared the efficacy of iPSC-derived the risk of altering the biological properties of MSCs. Such
MSCs with that of primary MSCs. The findings alterations may affect the composition, function, and
indicated that iPSC-derived MSCs and bone marrow- stability of exosomes, thereby impacting their therapeutic
derived MSCs displayed no significant difference efficacy and safety. Therefore, when developing MSC-
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in their ability to promote collagen synthesis and exo-based therapeutic strategies, it is essential to fully
angiogenesis, both effectively promoting skin wound consider the potential risks associated with modifications
healing. 67,68 In addition, JNKi- and DAC-programmed and to optimize the quality and function of exosomes
MSCs from human embryonic stem cells (hESC- through precise modifications and functional validation.
MSCs) exhibit similar adipogenic, osteogenic, and Future research should further explore the mechanisms
chondrogenic differentiation abilities as tissue-derived through which modifications affect MSCs and exosomes
MSCs. They also facilitate hematopoiesis and alleviate to advance their clinical applications.
hind limb ischemia. These findings suggest that
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iMSCs and hESC-MSCs are emerging as attractive 5. Conclusion
alternatives to traditional MSCs. MSC-exo is rich in various bioactive substances, including
(iii) Exosome isolation technology: The isolation nucleic acids, proteins, and lipids. As carriers of intercellular
technology of exosomes warrants further communication, MSC-exo exhibits both tumor-promoting
optimization. At present, the commonly used exosome and tumor-inhibiting effects. This further highlights the
isolation techniques, such as ultracentrifugation and potential of MSC-exo as novel anti-tumor drugs in clinical
commercial kit-based methods, do not meet the applications, providing new clinical options for anti-
needs of commercial production. Studies combining tumor therapy. However, since MSC-exo plays a critical
polyethylene glycol precipitation, dielectrophoresis, role in tumors, further research is warranted to mitigate
and deterministic lateral displacement (DLD) isolation the tumor-promoting effects of MSC-exo and expand its
methods indicate that integrating multiple isolation application as anti-tumor therapeutics.

Volume 2 Issue 3 (2025) 8 doi: 10.36922/IMO025210025