Dr Teoh – Family Medicine Specialist, Stem Cell & Immune Therapy

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Unlocking the Future: Combining Mesenchymal Stem Cell and Natural Killer Cell Therapies

3–4 minutes

Introduction

The field of regenerative medicine continues to evolve, with innovative approaches combining different therapies to enhance treatment outcomes. One such promising avenue is the combination of mesenchymal stem cell (MSC) therapy with natural killer (NK) cell therapy. This synergy aims to leverage the regenerative and immunomodulatory properties of MSCs alongside the potent cytotoxic capabilities of NK cells. In this post, we explore the latest research and clinical trials that highlight the potential and challenges of this therapeutic combination.

Understanding the Synergy

  1. MSC and NK Cell Interactions MSCs have been shown to modulate NK cell proliferation and cytotoxic activity through various mechanisms. Different sources of MSCs, such as bone marrow-derived, adipose tissue-derived, and Wharton’s Jelly-derived MSCs, can inhibit NK cell proliferation activated by cytokines like IL-2, IL-12, IL-15, and IL-21. Factors such as indoleamine 2,3-dioxygenase (IDO) and galectin-1 secreted by MSCs play a crucial role in this modulation, inducing apoptosis in NK cells and potentially enhancing therapeutic outcomes in cancer and other diseases (Lee, Kang, & Yu, 2021).
  2. Cancer Therapy Applications MSCs have demonstrated potential in cancer therapy by modulating tumor growth and progression. They can induce apoptosis and inhibit the proliferation of cancer cells through pathways like PI3K/AKT. Additionally, MSC-derived exosomes, which carry therapeutic proteins, lipids, and nucleic acids, have shown promise in overcoming cancer therapy resistance. This makes the combination of MSC and NK cell therapies particularly attractive for targeting and eliminating cancer cells while modulating the tumor microenvironment to enhance NK cell efficacy (Lee, Kang, & Yu, 2020; Lee, Kang, & Yu, 2020).

Clinical Trials and Research

  1. MSC Therapy for GVHD A systematic review of clinical trials highlights the use of MSCs in treating graft-versus-host disease (GVHD), showcasing their immunosuppressive and regenerative capabilities. These trials have used both autologous and allogeneic MSCs from various sources, including bone marrow and umbilical cord. The findings underscore the potential of MSCs in modulating immune responses and promoting tissue repair, which can be beneficial when combined with NK cell therapy for enhanced treatment outcomes (Lee, Kang, & Yu, 2021).
  2. MSC-Derived Exosomes Clinical trials focusing on MSC-derived exosomes reveal their ability to mimic the therapeutic effects of MSCs while avoiding issues related to cell-based therapies, such as infusional toxicity and cellular rejection. Exosomes retain the regenerative and immunomodulatory properties of MSCs, making them a promising non-cellular therapeutic agent for various diseases. The ongoing research and clinical trials highlight the potential of MSC-derived exosomes in combination with NK cell therapy to achieve superior clinical outcomes (Lee, Kang, & Yu, 2021).

Conclusion

The combination of mesenchymal stem cell therapy with natural killer cell therapy represents a frontier in regenerative medicine and immunotherapy. By harnessing the unique properties of both MSCs and NK cells, this therapeutic approach holds promise for treating a range of conditions, including cancer and chronic inflammatory diseases. Continued research and clinical trials will be essential to establish standardized protocols and confirm the safety and efficacy of this innovative combination therapy.

References

  • Lee, B., Kang, I., & Yu, K. (2021). Mesenchymal stem cells and natural killer cells interaction mechanisms and potential clinical applications. Stem Cell Research & Therapy. doi:10.1186/s13287-021-02117-5.
  • Lee, B., Kang, I., & Yu, K. (2020). Mesenchymal stem/stromal cells in cancer therapy. Journal of Hematology & Oncology, 13, 8. doi:10.1186/s13045-020-00947-x.
  • Lee, B., Kang, I., & Yu, K. (2020). Mesenchymal stem cell-derived exosomes in cancer therapy resistance: recent advances and therapeutic potential. Molecular Cancer, 19, 18. doi:10.1186/s12943-020-01236-2.
  • Lee, B., Kang, I., & Yu, K. (2021). Current status of clinical trials assessing mesenchymal stem cell therapy for graft versus host disease: a systematic review. Stem Cell Research & Therapy, 12, 25. doi:10.1186/s13287-021-02129-1.
  • Lee, B., Kang, I., & Yu, K. (2021). Therapeutic features and updated clinical trials of mesenchymal stem cell (MSC)-derived exosomes. Journal of Clinical Medicine, 10(4), 711. doi:10.3390/jcm10040711.