Reconstructing the Stem Leydig Cell Niche via the Testicular Extracellular Matrix for the Treatment of Testicular Leydig Cell Dysfunction
Abstract Therapies involving the use of stem Leydig cells (SLCs), as testicular mesenchymal stromal cells, have shown great promise in the treatment of Leydig cell (LC) dysfunction in aging males. However, the outcomes of these therapies are not satisfactory. In this study, it is demonstrated that t...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202410808 |
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| author | Ani Chi Chao Yang Jie Liu Zhichen Zhai Xuetao Shi |
| author_facet | Ani Chi Chao Yang Jie Liu Zhichen Zhai Xuetao Shi |
| author_sort | Ani Chi |
| collection | DOAJ |
| description | Abstract Therapies involving the use of stem Leydig cells (SLCs), as testicular mesenchymal stromal cells, have shown great promise in the treatment of Leydig cell (LC) dysfunction in aging males. However, the outcomes of these therapies are not satisfactory. In this study, it is demonstrated that the aging microenvironment of the testicular interstitium impairs the function of SLCs, leading to poor regeneration of LCs and, consequently, inefficient functional restoration. The study develops a decellularized testicular extracellular matrix (dTECM) hydrogel from young pigs and evaluates its safety and feasibility as a supportive niche for the expansion and differentiation of SLCs. dTECM hydrogel facilitates the steroidogenic differentiation of SLCs into LCs, the primary producers of testosterone. The combination of SLCs with a dTECM hydrogel leads to a significant and sustained increase in testosterone levels, which promotes the restoration of spermatogenesis and fertility in an LC‐deficient and aged mouse model. Mechanistically, collagen 1 within the dTECM is identified as a key factor contributing to these effects. Notably, symptoms associated with testosterone deficiency syndrome are significantly alleviated in aged mice. These findings may aid the design of therapeutic interventions for patients with testosterone deficiency in the clinic. |
| format | Article |
| id | doaj-art-190ce153cf1c4d5fa5374501326b3165 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-190ce153cf1c4d5fa5374501326b31652025-01-13T15:29:43ZengWileyAdvanced Science2198-38442025-01-01122n/an/a10.1002/advs.202410808Reconstructing the Stem Leydig Cell Niche via the Testicular Extracellular Matrix for the Treatment of Testicular Leydig Cell DysfunctionAni Chi0Chao Yang1Jie Liu2Zhichen Zhai3Xuetao Shi4National Engineering Research Centre for Tissue Restoration and Reconstruction Key Laboratory of Biomedical Engineering of Guangdong Province South China University of Technology Guangzhou 510640 P. R. ChinaNational Engineering Research Centre for Tissue Restoration and Reconstruction Key Laboratory of Biomedical Engineering of Guangdong Province South China University of Technology Guangzhou 510640 P. R. ChinaNational Engineering Research Centre for Tissue Restoration and Reconstruction Key Laboratory of Biomedical Engineering of Guangdong Province South China University of Technology Guangzhou 510640 P. R. ChinaNational Engineering Research Centre for Tissue Restoration and Reconstruction Key Laboratory of Biomedical Engineering of Guangdong Province South China University of Technology Guangzhou 510640 P. R. ChinaNational Engineering Research Centre for Tissue Restoration and Reconstruction Key Laboratory of Biomedical Engineering of Guangdong Province South China University of Technology Guangzhou 510640 P. R. ChinaAbstract Therapies involving the use of stem Leydig cells (SLCs), as testicular mesenchymal stromal cells, have shown great promise in the treatment of Leydig cell (LC) dysfunction in aging males. However, the outcomes of these therapies are not satisfactory. In this study, it is demonstrated that the aging microenvironment of the testicular interstitium impairs the function of SLCs, leading to poor regeneration of LCs and, consequently, inefficient functional restoration. The study develops a decellularized testicular extracellular matrix (dTECM) hydrogel from young pigs and evaluates its safety and feasibility as a supportive niche for the expansion and differentiation of SLCs. dTECM hydrogel facilitates the steroidogenic differentiation of SLCs into LCs, the primary producers of testosterone. The combination of SLCs with a dTECM hydrogel leads to a significant and sustained increase in testosterone levels, which promotes the restoration of spermatogenesis and fertility in an LC‐deficient and aged mouse model. Mechanistically, collagen 1 within the dTECM is identified as a key factor contributing to these effects. Notably, symptoms associated with testosterone deficiency syndrome are significantly alleviated in aged mice. These findings may aid the design of therapeutic interventions for patients with testosterone deficiency in the clinic.https://doi.org/10.1002/advs.202410808agingextracellular matrixLeydig cellstem Leydig cell |
| spellingShingle | Ani Chi Chao Yang Jie Liu Zhichen Zhai Xuetao Shi Reconstructing the Stem Leydig Cell Niche via the Testicular Extracellular Matrix for the Treatment of Testicular Leydig Cell Dysfunction Advanced Science aging extracellular matrix Leydig cell stem Leydig cell |
| title | Reconstructing the Stem Leydig Cell Niche via the Testicular Extracellular Matrix for the Treatment of Testicular Leydig Cell Dysfunction |
| title_full | Reconstructing the Stem Leydig Cell Niche via the Testicular Extracellular Matrix for the Treatment of Testicular Leydig Cell Dysfunction |
| title_fullStr | Reconstructing the Stem Leydig Cell Niche via the Testicular Extracellular Matrix for the Treatment of Testicular Leydig Cell Dysfunction |
| title_full_unstemmed | Reconstructing the Stem Leydig Cell Niche via the Testicular Extracellular Matrix for the Treatment of Testicular Leydig Cell Dysfunction |
| title_short | Reconstructing the Stem Leydig Cell Niche via the Testicular Extracellular Matrix for the Treatment of Testicular Leydig Cell Dysfunction |
| title_sort | reconstructing the stem leydig cell niche via the testicular extracellular matrix for the treatment of testicular leydig cell dysfunction |
| topic | aging extracellular matrix Leydig cell stem Leydig cell |
| url | https://doi.org/10.1002/advs.202410808 |
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