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Review

Therapeutic Efficacy of Interferon-Gamma and Hypoxia-Primed Mesenchymal Stromal Cells and Their Extracellular Vesicles: Underlying Mechanisms and Potentials in Clinical Translation

1
Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Kuala Lumpur 56000, Malaysia
2
NK Biocell Sdn. Bhd, Unit 1-22A, 1st Floor Pusat Perdagangan Berpadu (United Point), No.10, Jalan Lang Emas, Kuala Lumpur 51200, Malaysia
3
Department of Obstetrics & Gynaecology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
*
Author to whom correspondence should be addressed.
Biomedicines 2024, 12(6), 1369; https://doi.org/10.3390/biomedicines12061369
Submission received: 17 April 2024 / Revised: 31 May 2024 / Accepted: 6 June 2024 / Published: 20 June 2024
(This article belongs to the Section Gene and Cell Therapy)

Abstract

Multipotent mesenchymal stromal cells (MSCs) hold promises for cell therapy and tissue engineering due to their self-renewal and differentiation abilities, along with immunomodulatory properties and trophic factor secretion. Extracellular vesicles (EVs) from MSCs offer similar therapeutic effects. However, MSCs are heterogeneous and lead to variable outcomes. In vitro priming enhances MSC performance, improving immunomodulation, angiogenesis, proliferation, and tissue regeneration. Various stimuli, such as cytokines, growth factors, and oxygen tension, can prime MSCs. Two classical priming methods, interferon-gamma (IFN-γ) and hypoxia, enhance MSC immunomodulation, although standardized protocols are lacking. This review discusses priming protocols, highlighting the most commonly used concentrations and durations, along with mechanisms and in vivo therapeutics effects of primed MSCs and their EVs. The feasibility of up-scaling their production was also discussed. The review concluded that priming with IFN-γ or hypoxia (alone or in combination with other factors) boosted the immunomodulation capability of MSCs and their EVs, primarily via the JAK/STAT and PI3K/AKT and Leptin/JAK/STAT and TGF-β/Smad signalling pathways, respectively. Incorporating priming in MSC and EV production enables translation into cell-based or cell-free therapies for various disorders.
Keywords: mesenchymal stromal cells; extracellular vesicles; priming; interferon-gamma; hypoxia; pre-clinical mesenchymal stromal cells; extracellular vesicles; priming; interferon-gamma; hypoxia; pre-clinical

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MDPI and ACS Style

Tan, Y.L.; Al-Masawa, M.E.; Eng, S.P.; Shafiee, M.N.; Law, J.X.; Ng, M.H. Therapeutic Efficacy of Interferon-Gamma and Hypoxia-Primed Mesenchymal Stromal Cells and Their Extracellular Vesicles: Underlying Mechanisms and Potentials in Clinical Translation. Biomedicines 2024, 12, 1369. https://doi.org/10.3390/biomedicines12061369

AMA Style

Tan YL, Al-Masawa ME, Eng SP, Shafiee MN, Law JX, Ng MH. Therapeutic Efficacy of Interferon-Gamma and Hypoxia-Primed Mesenchymal Stromal Cells and Their Extracellular Vesicles: Underlying Mechanisms and Potentials in Clinical Translation. Biomedicines. 2024; 12(6):1369. https://doi.org/10.3390/biomedicines12061369

Chicago/Turabian Style

Tan, Yu Ling, Maimonah Eissa Al-Masawa, Sue Ping Eng, Mohamad Nasir Shafiee, Jia Xian Law, and Min Hwei Ng. 2024. "Therapeutic Efficacy of Interferon-Gamma and Hypoxia-Primed Mesenchymal Stromal Cells and Their Extracellular Vesicles: Underlying Mechanisms and Potentials in Clinical Translation" Biomedicines 12, no. 6: 1369. https://doi.org/10.3390/biomedicines12061369

APA Style

Tan, Y. L., Al-Masawa, M. E., Eng, S. P., Shafiee, M. N., Law, J. X., & Ng, M. H. (2024). Therapeutic Efficacy of Interferon-Gamma and Hypoxia-Primed Mesenchymal Stromal Cells and Their Extracellular Vesicles: Underlying Mechanisms and Potentials in Clinical Translation. Biomedicines, 12(6), 1369. https://doi.org/10.3390/biomedicines12061369

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