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Mesenchymal stem cells-derived secretome and extracellular vesicles: perspective and challenges in cancer therapy and clinical applications

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Abstract

Stem cell-based therapies have been foreshowed as a promising therapeutic approach for the treatment of several diseases. However, in the cancer context, results obtained from clinical studies were found to be quite limited. Deeply implicated in inflammatory cues, Mesenchymal, Neural, and Embryonic Stem Cells have mainly been used in clinical trials as a vehicle to deliver and stimulate signals in tumors niche. Although these stem cells have shown some therapeutical promises, they still face several challenges, including their isolation, immunosuppression potential, and tumorigenicity. In addition, regulatory and ethical concerns limit their use in several countries. Mesenchymal stem cells (MSC) have emerged as a gold standard adult stem cell medicine tool due to their distinctive characteristics, such as self-renewal and potency to differentiate into numerous cell types with lower ethical restrictions. Secreted extracellular vesicles (EVs), secretomes, and exosomes play a crucial role in mediating cell-to-cell communication to maintain physiological homeostasis and influence pathogenesis. Due to their low immunogenicity, biodegradability, low toxicity, and ability to transfer bioactive cargoes across biological barriers, EVs and exosomes were considered an alternative to stem cell therapy through their immunological features. MSCs-derived EVs, exosomes, and secretomes showed regenerative, anti-inflammatory, and immunomodulation properties while treating human diseases. In this review, we provide an overview of the paradigm of MSCs derived exosomes, secretome, and EVs cell-free-based therapies, we will focus on MSCs-derived components in anti-cancer treatment with decreased risk of immunogenicity and toxicity. Astute exploration of MSCs may lead to a new opportunity for efficient therapy for patients with cancer.

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Data availability statement

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

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Authors and Affiliations

  1. Faculty of Health Sciences, Balamand University, Beirut, Lebanon

    Jack Gemayel

  2. INSERM, National Institute of Health and Medical Research, Paris XI, Paris, France

    Diana Chaker

  3. Reviva Stem Cell Platform for Research and Applications Center, Bsalim, Lebanon

    Diana Chaker, Rawad Salemeh, Ahmad Ibrahim & Charbel Khalil

  4. Balamand University, Faculty of Medicine, Beirut, Lebanon

    Georges El Hachem & Ahmad Ibrahim

  5. Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, Al Kurah, P.O. Box 100, Kalhat, Lebanon

    Georges El Hachem & Frederic Harb

  6. Faculty of Medicine, Saint Joseph University, Beirut, Lebanon

    Melissa Mhanna

  7. Faculty of Medicine, Lebanese American University Medical Center, Rizk Hospital, Beirut, Lebanon

    Colette Hanna

  8. Medical Genetics Unit, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon

    Alain Chebly

  9. Higher Institute of Public Health, Saint Joseph University, Beirut, Lebanon

    Alain Chebly

  10. Bone Marrow Transplant Unit, Burjeel Medical City, Abu Dhabi, UAE

    Charbel Khalil

  11. Stem Cell Institute, Faculty of Medical Sciences, Lebanese University, Beirut, Lebanon

    Charbel Khalil

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  1. Jack Gemayel
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JG, DC, AC, CH, GH, AI, RS, MM, and CK wrote the manuscript.

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Correspondence to Charbel Khalil.

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Gemayel, J., Chaker, D., El Hachem, G. et al. Mesenchymal stem cells-derived secretome and extracellular vesicles: perspective and challenges in cancer therapy and clinical applications. Clin Transl Oncol 25, 2056–2068 (2023). https://doi.org/10.1007/s12094-023-03115-7

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