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Sertoli Cells Possess Immunomodulatory Properties and the Ability of Mitochondrial Transfer Similar to Mesenchymal Stromal Cells

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Abstract

It is becoming increasingly evident that selecting an optimal source of mesenchymal stromal cells (MSCs) is crucial for the successful outcome of MSC-based therapies. During the search for cells with potent regenerative properties, Sertoli cells (SCs) have been proven to modulate immune response in both in vitro and in vivo models. Based on morphological properties and expression of surface markers, it has been suggested that SCs could be a kind of MSCs, however, this hypothesis has not been fully confirmed. Therefore, we compared several parameters of MSCs and SCs, with the aim to evaluate the therapeutic potential of SCs in regenerative medicine. We showed that SCs successfully underwent osteogenic, chondrogenic and adipogenic differentiation and determined the expression profile of canonical MSC markers on the SC surface. Besides, SCs rescued T helper (Th) cells from undergoing apoptosis, promoted the anti-inflammatory phenotype of these cells, but did not regulate Th cell proliferation. MSCs impaired the Th17-mediated response; on the other hand, SCs suppressed the inflammatory polarisation in general. SCs induced M2 macrophage polarisation more effectively than MSCs. For the first time, we demonstrated here the ability of SCs to transfer mitochondria to immune cells. Our results indicate that SCs are a type of MSCs and modulate the reactivity of the immune system. Therefore, we suggest that SCs are promising candidates for application in regenerative medicine due to their anti-inflammatory and protective effects, especially in the therapies for diseases associated with testicular tissue inflammation.

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Funding

This study was supported by grant No. 970120 from the Grant Agency of Charles University, grant No. 19-02290S from the Grant Agency of the Czech Republic, grant No. NU21-08–00488 from Ministry of Health of the Czech Republic and the Charles University programs 4EU + /20/F4/29, SVV 260435 and 20604315 PROGRES Q43.

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Authors and Affiliations

  1. Department of Cell Biology, Faculty of Science, Charles University, Vinicna 7, Prague 2, 128 43, Vídeňská, Czech Republic

    Bianka Porubska, Daniel Vasek, Veronika Somova, Michaela Hajkova, Michaela Hlaviznova, Tereza Tlapakova, Vladimir Holan & Magdalena Krulova

  2. Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague 4, 142 20, Vídeňská, 1083, Czech Republic

    Bianka Porubska, Michaela Hajkova, Vladimir Holan & Magdalena Krulova

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  1. Bianka Porubska
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All authors contributed to this study. MK and BP designed the study. BP, DV, VS, MHa, MHl and TT performed the experiments, MK, BP, and VH wrote the paper; all authors read and approved the final manuscript.

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Correspondence to Magdalena Krulova.

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This study was carried out in strict accordance with the Act No. 246/1992 Coll., on the protection of animals against cruelty, the basic law related to animal protection governing the activities of all the state authorities of animal protection in the Czech Republic, such as the Ministry of Agriculture, including the Central Commission for Animal Welfare, and the veterinary administration authorities. The authorization to use experimental animals was issued to the Faculty of Science, Charles University, 37,428/2019-MZE-18134.

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Porubska, B., Vasek, D., Somova, V. et al. Sertoli Cells Possess Immunomodulatory Properties and the Ability of Mitochondrial Transfer Similar to Mesenchymal Stromal Cells. Stem Cell Rev and Rep 17, 1905–1916 (2021). https://doi.org/10.1007/s12015-021-10197-9

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