Medical Research and Education Center, Lomonosov Moscow State University, Moscow, Russian Federation; Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russian Federation.
Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russian Federation.
Biomed Pharmacother. 2019 Jan;109:1428-1436. doi: 10.1016/j.biopha.2018.10.174. Epub 2018 Nov 13.
Male infertility represents a severe social and medical challenge. In recent years the progress in regenerative medicine promoted the development of novel options to overcome this medical condition. We are elaborating a promising approach to restore spermatogenesis using mesenchymal stromal cell (MSC) secretome components as a novel class of cell-free cell therapy medicinal products for regenerative medicine. However, the choice of the representative in vivo model of spermatogenesis failure to evaluate the effectiveness of regenerative drugs remains challenging. Using the rat model of bilateral abdominal cryptorchidism, we studied the contribution of MSC conditioned medium contained bioactive cell secreted products to the spermatogenesis recovery. The feasibility of this model to evaluate the drug-driven regenerative effects on spermatogenesis restoration after the injury was demonstrated. We revealed significant correlations between the extent of spermatogonial stem cell niche recovery, spermatozoa count and serum concentration of androgens as an indicator of Leydig cell function. The obtained results can be applied in preclinical studies to choose the proper criteria to appraise the specific activity of novel regenerative drugs developed for the treatment of non-obstructive spermatogenesis disorders.
男性不育症是一个严重的社会和医学挑战。近年来,再生医学的进展推动了新方法的发展,以克服这种医学状况。我们正在详细研究一种有前途的方法,即用间充质基质细胞 (MSC) 分泌组成分恢复精子发生,作为一种新型的无细胞细胞治疗药物产品用于再生医学。然而,选择代表精子发生衰竭的体内模型来评估再生药物的有效性仍然具有挑战性。我们使用双侧腹部隐睾大鼠模型,研究了 MSC 条件培养基中包含的生物活性细胞分泌产物对精子发生恢复的贡献。该模型证明了在损伤后评估药物驱动的再生对精子发生恢复的作用的可行性。我们揭示了精原干细胞龛恢复的程度、精子计数和血清雄激素浓度之间的显著相关性,雄激素浓度作为睾丸间质细胞功能的指标。所得结果可应用于临床前研究,以选择适当的标准来评估为治疗非阻塞性精子发生障碍而开发的新型再生药物的特定活性。