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Extension of Survival in Bilaterally Adrenalectomized Mice by Implantation of SF-1/Ad4BP-Induced Steroidogenic Cells.

通过植入SF-1/Ad4BP-Induced类固醇生成细胞延长双侧肾上腺切除小鼠的存活。

  • 影响因子:3.62
  • DOI:10.1210/endocr/bqaa007
  • 作者列表:"Tanaka T","Aoyagi C","Mukai K","Nishimoto K","Kodama S","Yanase T
  • 发表时间:2020-03-01
Abstract

:Mesenchymal stroma/stem cells (MSCs) exist in adult tissues, such as adipose tissue and bone marrow, and differentiate into cells of multiple lineages. In previous studies, we found that MSCs differentiate into steroidogenic cells by forced expression of steroidogenic factor 1 (SF-1)/adrenal 4 binding protein (Ad4BP), the master regulator of steroidogenesis and differentiation of pituitary gonadotrophs, adrenal glands, and gonads. In this study, SF-1/Ad4BP-induced steroidogenic cells derived from mouse adipose tissue-derived MSCs (ADSCs) were implanted under the kidney capsule of bilateral adrenalectomized (bAdx) mice. bAdx mice did not survive after 7 days. However, 4 of 9 bAdx mice implanted with SF-1/Ad4BP-induced steroidogenic cells, 1 of 10 bAdx mice transplanted with control ADSCs, and bAdx mice transplanted with an adrenal gland survived for 30 days. Plasma corticosterone levels in bAdx mice implanted with SF-1/Ad4BP-induced steroidogenic cells and control ADSCs were 5.41 ± 2.26 ng/mL (mean ± SEM) and undetectable at 7 days after implantation, respectively. After removal of the kidney bearing the graft from the surviving mice at 30 days after implantation, plasma corticosterone was not detected in any of the samples. Immunohistochemical staining revealed SF-1/Ad4BP-positive cells under the capsule of the kidney. Although we performed an adrenocorticotropin (ACTH) loading test on bAdx mice implanted with SF-1/Ad4BP-induced steroidogenic cells, ACTH responsiveness was not observed. Implantation of steroidogenic cells derived from ADSCs into bAdx mice increased the basal plasma corticosterone level and extended the survival of bAdx mice, suggesting the capability of restoring steroidogenic cells by cell transplantation therapy for adrenal insufficiency.

摘要

: 间充质基质/干细胞 (msc) 存在于成人组织,如脂肪组织和骨髓中,并分化为多个谱系的细胞。在以前的研究中,我们发现MSCs通过强迫表达类固醇生成因子1 (SF-1)/肾上腺4结合蛋白 (Ad4BP) 分化为类固醇生成细胞,这是类固醇生成和垂体促性腺激素、肾上腺和性腺分化的主要调控因子。在本研究中,将来源于小鼠脂肪组织来源的msc (ADSCs) 的SF-1/Ad4BP-induced类固醇生成细胞植入双侧肾上腺切除 (bAdx) 小鼠的肾被膜下。bAdx小鼠在7天后没有存活。然而,植入SF-1/Ad4BP-induced类固醇生成细胞的9只bAdx小鼠中的4只、移植有对照adsc的10只bAdx小鼠中的1只和移植有肾上腺的bAdx小鼠存活30天。植入SF-1/Ad4BP-induced类固醇生成细胞的bAdx小鼠和对照adsc的血浆皮质酮水平分别为5.41 ± 2.26 ng/mL (平均值 ± sem),植入后7天检测不到。在植入后30天从存活的小鼠取出带有移植物的肾后,在任何样品中均未检测到血浆皮质酮。免疫组化染色显示肾被膜下有SF-1/Ad4BP-positive个细胞。尽管我们对植入了SF-1/Ad4BP-induced类固醇生成细胞的bAdx小鼠进行了促肾上腺皮质激素 (ACTH) 负荷试验,但没有观察到ACTH反应性。将来源于ADSCs的类固醇生成细胞植入bAdx小鼠增加了基础血浆皮质酮水平并延长了bAdx小鼠的存活,表明通过细胞移植治疗肾上腺功能不全恢复类固醇生成细胞的能力。

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影响因子:4.46
发表时间:2020-03-01
DOI:10.1111/nyas.14205
作者列表:["Fan L","Zhuang Y","Wang Y","Liu X","Liu D","Xiang B","He M","Zhang Z","Li Y","Wang Y","Zhu X","Ye H"]

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影响因子:6.93
发表时间:2020-04-15
DOI:10.1002/ijc.32654
作者列表:["Ghosal S","Das S","Pang Y","Gonzales MK","Huynh TT","Yang Y","Taieb D","Crona J","Shankavaram UT","Pacak K"]

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肾上腺疾病方向

主要包括肾上腺皮质疾病、肾上腺肿瘤、先天性肾上腺增生、肾上腺机能不全、肾上腺皮质机能亢进等疾病。

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