Department of Physiology, School of Veterinary Medicine, Complutense University of Madrid, Avda. Puerta de Hierro SN, Madrid, 28040, Spain.
Department of Animal Medicine and Surgery, School of Veterinary Medicine, Complutense University of Madrid, Madrid, 28040, Spain.
BMC Vet Res. 2024 Aug 20;20(1):372. doi: 10.1186/s12917-024-04203-8.
Neural stem and progenitor cells (NSPCs) from extra-neural origin represent a valuable tool for autologous cell therapy and research in neurogenesis. Identification of proneurogenic biomolecules on NSPCs would improve the success of cell therapies for neurodegenerative diseases. Preliminary data suggested that follicle-stimulating hormone (FSH) might act in this fashion. This study was aimed to elucidate whether FSH promotes development, self-renewal, and is proneurogenic on neurospheres (NS) derived from sheep ovarian cortical cells (OCCs). Two culture strategies were carried out: (a) long-term, 21-days NS culture (control vs. FSH group) with NS morphometric evaluation, gene expression analyses of stemness and lineage markers, and immunolocalization of NSPCs antigens; (b) NS assay to demonstrate FSH actions on self-renewal and differentiation capacity of NS cultured with one of three defined media: M1: positive control with EGF/FGF2; M2: control; and M3: M2 supplemented with FSH.
In long-term cultures, FSH increased NS diameters with respect to control group (302.90 ± 25.20 μm vs. 183.20 ± 7.63 on day 9, respectively), upregulated nestin (days 15/21), Sox2 (day 21) and Pax6 (days 15/21) and increased the percentages of cells immunolocalizing these proteins. During NS assays, FSH stimulated NSCPs proliferation, and self-renewal, increasing NS diameters during the two expansion periods and the expression of the neuron precursor transcript DCX during the second one. In the FSH-group there were more frequent cell-bridges among neighbouring NS.
FSH is a proneurogenic hormone that promotes OCC-NSPCs self-renewal and NS development. Future studies will be necessary to support the proneurogenic actions of FSH and its potential use in basic and applied research related to cell therapy.
源于神经外组织的神经干/祖细胞（NSPCs）是自体细胞疗法和神经发生研究的宝贵工具。鉴定 NSPCs 上的神经前体细胞生物分子将提高神经退行性疾病细胞疗法的成功率。初步数据表明，卵泡刺激素（FSH）可能具有这种作用。本研究旨在阐明 FSH 是否促进源自绵羊卵巢皮质细胞（OCCs）的神经球（NS）的发育、自我更新和神经前体细胞特性。进行了两种培养策略：（a）长期 21 天 NS 培养（对照与 FSH 组），对 NS 形态计量学评估、干性和谱系标志物的基因表达分析，以及 NSPCs 抗原的免疫定位；（b）NS 测定，以证明 FSH 对用三种定义培养基之一培养的 NS 的自我更新和分化能力的作用：M1：含 EGF/FGF2 的阳性对照；M2：对照；M3：M2 补充 FSH。
在长期培养中，与对照组相比，FSH 增加了 NS 的直径（第 9 天分别为 302.90±25.20μm 和 183.20±7.63μm），上调了 nestin（第 15/21 天）、Sox2（第 21 天）和 Pax6（第 15/21 天），并增加了这些蛋白质免疫定位的细胞百分比。在 NS 测定中，FSH 刺激 NSCPs 的增殖和自我更新，在两个扩增期增加 NS 的直径，并在第二个扩增期增加神经元前体转录本 DCX 的表达。在 FSH 组中，相邻 NS 之间的细胞桥更为频繁。
FSH 是一种神经前体细胞激素，可促进 OCC-NSPCs 的自我更新和 NS 的发育。未来的研究将有必要支持 FSH 的神经前体细胞作用及其在与细胞疗法相关的基础和应用研究中的潜在用途。
