Department of Cell Biology, Faculty of Science, Charles University, Vinicna 7, Prague, 2, 128 00, Czech Republic.
Laboratory of Reproductive Biology, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Vestec, Prumyslova 595, Prague, 252 50, Czech Republic.
Stem Cell Res Ther. 2024 Sep 4;15(1):282. doi: 10.1186/s13287-024-03897-9.
Inflammation-induced testicular damage is a significant contributing factor to the increasing incidence of infertility. Traditional treatments during the inflammatory phase often fail to achieve the desired fertility outcomes, necessitating innovative interventions such as cell therapy.
We explored the in vivo properties of intravenously administered Sertoli cells (SCs) in an acute lipopolysaccharide (LPS)-induced inflammatory mouse model. Infiltrating and resident myeloid cell phenotypes were assessed using flow cytometry. The impact of SC administration on testis morphology and germ cell quality was evaluated using computer-assisted sperm analysis (CASA) and immunohistochemistry.
SCs demonstrated a distinctive migration pattern, importantly they preferentially concentrated in the testes and liver. SC application significantly reduced neutrophil infiltration as well as preserved the resident macrophage subpopulations. SCs upregulated MerTK expression in both interstitial and peritubular macrophages. Applied SC treatment exhibited protective effects on sperm including their motility and kinematic parameters, and maintained the physiological testicular morphology.
Our study provides compelling evidence of the therapeutic efficacy of SC transplantation in alleviating acute inflammation-induced testicular damage. These findings contribute to the expanding knowledge on the potential applications of cell-based therapies for addressing reproductive health challenges and offer a promising approach for targeted interventions in male infertility.
炎症引起的睾丸损伤是导致不孕发病率上升的一个重要因素。在炎症阶段的传统治疗方法往往无法达到预期的生育效果，因此需要创新干预措施，如细胞疗法。
我们在急性脂多糖（LPS）诱导的炎症小鼠模型中研究了静脉内给予支持细胞（SCs）的体内特性。使用流式细胞术评估浸润和固有髓样细胞表型。使用计算机辅助精子分析（CASA）和免疫组织化学评估 SC 给药对睾丸形态和生精细胞质量的影响。
SCs 表现出独特的迁移模式，重要的是，它们优先集中在睾丸和肝脏中。SC 应用显著减少了中性粒细胞浸润，并保留了固有巨噬细胞亚群。SCs 在间质和小管周围巨噬细胞中上调了 MerTK 表达。应用 SC 治疗对精子具有保护作用，包括其运动和运动学参数，并维持了生理睾丸形态。
我们的研究提供了令人信服的证据，证明 SC 移植在缓解急性炎症引起的睾丸损伤方面具有治疗效果。这些发现有助于扩展细胞疗法在解决生殖健康挑战方面的潜在应用的知识，并为男性不育的靶向干预提供了一种有前途的方法。
