PDF(Pubmed)
Abstract：
Cell therapy for adrenocortical insufficiency can potentially provide steroid replacement in response to physiological stimuli. Previously, we reported that adipose tissue-derived stromal cells (ADSCs) are transformed into steroid-producing cells by overexpression of nuclear receptor subfamily 5 group A member 1 (NR5A1). The steroidogenic cells are characterized by the production of both adrenal and gonadal steroids. Cytotherapy for adrenocortical insufficiency requires cells with more adrenocortical characteristics. Considering the highly developed vascular network within the adrenal cortex, all adrenocortical cells are adjacent to and interact with vascular endothelial cells (VECs). In this study, NR5A1-induced steroidogenic cells derived from mouse ADSCs (NR5A1-ADSCs) were co-cultured with mouse VECs. Testosterone secretion in NR5A1-ADSCs was not altered; however, corticosterone secretion significantly increased while levels of steroidogenic enzymes significantly increased in the corticosterone synthesis pathway. Co-culture with lymphatic endothelial cells (LECs) or ADSCs, or transwell culture with NR5A1-ADSCs and VECs did not alter corticosterone production. VECs expressed higher levels of collagen and laminin than LECs. Culture in type-IV collagen and laminin-coated dishes increased corticosterone secretion in NR5A1-ADSCs. These results suggest that VECs may characterize ADSC-derived steroidogenic cells into a more corticosterone-producing phenotype, and VECs may be useful for generating adrenal steroidogenic cells from stem cells.
摘要：
肾上腺皮质功能不全的细胞疗法可以潜在地提供响应于生理刺激的类固醇替代。以前,我们报道了脂肪组织来源的基质细胞(ADSC)通过核受体亚家族5组A成员1(NR5A1)的过表达而转化为类固醇生成细胞.类固醇生成细胞的特征在于产生肾上腺和性腺类固醇。肾上腺皮质功能不全的细胞治疗需要具有更多肾上腺皮质特征的细胞。考虑到肾上腺皮质内高度发达的血管网络，所有肾上腺皮质细胞与血管内皮细胞(VEC)相邻并相互作用.在这项研究中,将源自小鼠ADSC的NR5A1诱导的类固醇生成细胞(NR5A1-ADSC)与小鼠VEC共培养。NR5A1-ADSCs的睾酮分泌没有改变；然而，在皮质酮合成途径中，皮质酮分泌显着增加，而类固醇生成酶的水平显着增加。与淋巴内皮细胞（LECs）或ADSCs共培养，或与NR5A1-ADSCs和VECs的transwell培养没有改变皮质酮的产生。VEC比LEC表达更高水平的胶原蛋白和层粘连蛋白。IV型胶原蛋白和层粘连蛋白包被的培养皿中的培养增加了NR5A1-ADSC的皮质酮分泌。这些结果表明，VECs可能将ADSC衍生的类固醇细胞表征为更多的皮质酮产生表型，和VEC可用于从干细胞产生肾上腺类固醇细胞。
