Immunomodulatory role of Xenopus tropicalis immature Sertoli cells in tadpole muscle regeneration via macrophage response modulation

Abstract Background Regenerative medicine and transplantation science continuously seek methods to circumvent immune-mediated rejection and promote tissue regeneration. Sertoli cells, with their inherent immunoprotective properties, emerge as pivotal players in this quest. However, whether Sertoli c...

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Main Authors: Qing Zhao, Irem Mertová, Aneta Wróblová, Světlana Žabková, Tereza Tlapáková, Vladimir Krylov
Format: Article
Language:English
Published: BMC 2024-11-01
Series:Stem Cell Research & Therapy
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Online Access:https://doi.org/10.1186/s13287-024-04050-2
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author Qing Zhao
Irem Mertová
Aneta Wróblová
Světlana Žabková
Tereza Tlapáková
Vladimir Krylov
author_facet Qing Zhao
Irem Mertová
Aneta Wróblová
Světlana Žabková
Tereza Tlapáková
Vladimir Krylov
author_sort Qing Zhao
collection DOAJ
description Abstract Background Regenerative medicine and transplantation science continuously seek methods to circumvent immune-mediated rejection and promote tissue regeneration. Sertoli cells, with their inherent immunoprotective properties, emerge as pivotal players in this quest. However, whether Sertoli cells can play immunomodulatory role in tadpole tail regeneration and can thus benefit the regeneration process are needed to be discovered. Methods Immature Sertoli cells from Xenopus tropicalis (XtiSCs) were transplanted into X. tropicalis tadpoles, followed by the amputation of the final third of their tails. We assessed the migration of XtiSCs, tail regeneration length, muscle degradation and growth, and macrophage counts across various regions including the entire tail, tail trunk, injection site, and regeneration site. The interactions between XtiSCs and macrophages were examined using a confocal microscope. To deplete macrophages, clodronate liposomes were administered prior to the transplantation of XtiSCs, while the administration of control liposomes acted as a negative control. Student’s t-test was used to compare the effects of XtiSCs injection to those of a 2/3PBS injection across groups with no liposomes, control liposomes, and clodronate liposomes. Results XtiSCs have excellent viability after transplantation to tadpole tail and remarkable homing capabilities to the regeneration site after tail amputation. XtiSCs injection increased macrophage numbers at 3 days post-amputation and 5 days post-amputation in the tail trunk, specifically at the injection site and at the regenerated tail, in a macrophage depleted environment (clodronate-liposome injection). What’s more, XtiSCs injection decreased muscle fibers degradation significantly at 1 day post-amputation and facilitated new muscle growth significantly at 3 days post-amputation. In addition, whole-mount immunostaining showed that some XtiSCs co-localized with macrophages. And we observed potential mitochondria transport from XtiSCs to macrophages using MitoTracker staining in tadpole tail. Conclusions Our study delineates the novel role of XtiSCs in facilitating muscle regeneration post tadpole tail amputation, underscoring a unique interaction with macrophages that is crucial for regenerative success. This study not only highlights the therapeutic potential of Sertoli cells in regenerative medicine but also opens avenues for clinical translation, offering insights into immunoregulatory strategies that could enhance tissue regeneration and transplant acceptance.
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spelling doaj-art-d06ed6af5a6b492197f47385df62c4d72024-11-17T12:13:06ZengBMCStem Cell Research & Therapy1757-65122024-11-0115111210.1186/s13287-024-04050-2Immunomodulatory role of Xenopus tropicalis immature Sertoli cells in tadpole muscle regeneration via macrophage response modulationQing Zhao0Irem Mertová1Aneta Wróblová2Světlana Žabková3Tereza Tlapáková4Vladimir Krylov5Department of Cell Biology, Faculty of Science, Charles UniversityDepartment of Cell Biology, Faculty of Science, Charles UniversityDepartment of Cell Biology, Faculty of Science, Charles UniversityDepartment of Cell Biology, Faculty of Science, Charles UniversityDepartment of Cell Biology, Faculty of Science, Charles UniversityDepartment of Cell Biology, Faculty of Science, Charles UniversityAbstract Background Regenerative medicine and transplantation science continuously seek methods to circumvent immune-mediated rejection and promote tissue regeneration. Sertoli cells, with their inherent immunoprotective properties, emerge as pivotal players in this quest. However, whether Sertoli cells can play immunomodulatory role in tadpole tail regeneration and can thus benefit the regeneration process are needed to be discovered. Methods Immature Sertoli cells from Xenopus tropicalis (XtiSCs) were transplanted into X. tropicalis tadpoles, followed by the amputation of the final third of their tails. We assessed the migration of XtiSCs, tail regeneration length, muscle degradation and growth, and macrophage counts across various regions including the entire tail, tail trunk, injection site, and regeneration site. The interactions between XtiSCs and macrophages were examined using a confocal microscope. To deplete macrophages, clodronate liposomes were administered prior to the transplantation of XtiSCs, while the administration of control liposomes acted as a negative control. Student’s t-test was used to compare the effects of XtiSCs injection to those of a 2/3PBS injection across groups with no liposomes, control liposomes, and clodronate liposomes. Results XtiSCs have excellent viability after transplantation to tadpole tail and remarkable homing capabilities to the regeneration site after tail amputation. XtiSCs injection increased macrophage numbers at 3 days post-amputation and 5 days post-amputation in the tail trunk, specifically at the injection site and at the regenerated tail, in a macrophage depleted environment (clodronate-liposome injection). What’s more, XtiSCs injection decreased muscle fibers degradation significantly at 1 day post-amputation and facilitated new muscle growth significantly at 3 days post-amputation. In addition, whole-mount immunostaining showed that some XtiSCs co-localized with macrophages. And we observed potential mitochondria transport from XtiSCs to macrophages using MitoTracker staining in tadpole tail. Conclusions Our study delineates the novel role of XtiSCs in facilitating muscle regeneration post tadpole tail amputation, underscoring a unique interaction with macrophages that is crucial for regenerative success. This study not only highlights the therapeutic potential of Sertoli cells in regenerative medicine but also opens avenues for clinical translation, offering insights into immunoregulatory strategies that could enhance tissue regeneration and transplant acceptance.https://doi.org/10.1186/s13287-024-04050-2Immature sertoli cellsXenopusTadpoleRegenerationMacrophages
spellingShingle Qing Zhao
Irem Mertová
Aneta Wróblová
Světlana Žabková
Tereza Tlapáková
Vladimir Krylov
Immunomodulatory role of Xenopus tropicalis immature Sertoli cells in tadpole muscle regeneration via macrophage response modulation
Stem Cell Research & Therapy
Immature sertoli cells
Xenopus
Tadpole
Regeneration
Macrophages
title Immunomodulatory role of Xenopus tropicalis immature Sertoli cells in tadpole muscle regeneration via macrophage response modulation
title_full Immunomodulatory role of Xenopus tropicalis immature Sertoli cells in tadpole muscle regeneration via macrophage response modulation
title_fullStr Immunomodulatory role of Xenopus tropicalis immature Sertoli cells in tadpole muscle regeneration via macrophage response modulation
title_full_unstemmed Immunomodulatory role of Xenopus tropicalis immature Sertoli cells in tadpole muscle regeneration via macrophage response modulation
title_short Immunomodulatory role of Xenopus tropicalis immature Sertoli cells in tadpole muscle regeneration via macrophage response modulation
title_sort immunomodulatory role of xenopus tropicalis immature sertoli cells in tadpole muscle regeneration via macrophage response modulation
topic Immature sertoli cells
Xenopus
Tadpole
Regeneration
Macrophages
url https://doi.org/10.1186/s13287-024-04050-2
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