Medical Research and Education Center, Lomonosov Moscow State University, Moscow, Russian Federation.
Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russian Federation.
Stem Cell Res Ther. 2019 Nov 21;10(1):342. doi: 10.1186/s13287-019-1479-3.
Injury of stem cell niches may disturb tissue homeostasis and regeneration coordinated by specific niche components. Yet, the mechanisms of stem cell niche restoration remain poorly understood. Herein, we examined the role of mesenchymal stromal cells (MSCs) as pivotal regulators of stem cell niche recovery focusing on the effects of their secretome.
The spermatogonial stem cell (SSC) niche was selected as a model. SSC niches were injured by inducing abdominal cryptorchidism in rats. Briefly, testes of anesthetized rats were elevated into the abdominal cavity through the inguinal canal for 14 days. After descent of testes, MSC or MSC secretome treatment was applied to the animals by local subtunical injections.
Local administration of MSC or MSC secretome was sufficient to recover spermatogenesis and production of functional germ cells. The effects of MSC and their secreted components were comparable, leading to restoration of Sertoli cell pools and recovery of Leydig cell secretory functions.
Our data suggest that MSCs mimic the functions of lost supportive cells within the stem cell niche, transiently providing paracrine stimuli for target cells and triggering tissue regenerative processes after damage.
干细胞龛的损伤可能会破坏由特定龛成分协调的组织稳态和再生。然而,干细胞龛恢复的机制仍知之甚少。本文中,我们研究了间充质基质细胞(MSCs)作为干细胞龛恢复关键调节因子的作用,重点研究了其分泌组的作用。
选择精原干细胞(SSC)龛作为模型。通过诱导大鼠腹部隐睾来损伤 SSC 龛。简而言之,通过腹股沟管将麻醉大鼠的睾丸抬高到腹腔中 14 天。睾丸下降后,通过局部皮下注射将 MSC 或 MSC 分泌组施用于动物。
局部给予 MSC 或 MSC 分泌组足以恢复精子发生和功能性生殖细胞的产生。MSC 及其分泌成分的作用相当,导致 Sertoli 细胞池的恢复和 Leydig 细胞分泌功能的恢复。
我们的数据表明,MSCs 模拟了干细胞龛中丢失的支持细胞的功能,短暂地为靶细胞提供旁分泌刺激,并在损伤后触发组织再生过程。