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小鼠子宫间充质干细胞及其对骨质疏松症的治疗作用。

Mesenchymal Stem Cell in Mice Uterine and Its Therapeutic Effect on Osteoporosis.

机构信息

Department of Biochemistry and Molecular Biology, Basic Medical College of Shanxi Medical University, Taiyuan, China.

Department of Obstetrics and Gynecology, Second Hospital of Shanxi Medical University, Taiyuan, China.

出版信息

Rejuvenation Res. 2021 Apr;24(2):139-150. doi: 10.1089/rej.2019.2262. Epub 2020 Nov 3.

DOI:10.1089/rej.2019.2262
PMID:32567490
Abstract

Osteoporosis is a silent disease caused by low bone mineral density and is complicated by fractures. This study was designed to examine the differentiation of uterine stem cell-derived osteoprogenitor cells (UOPCs) both and , assessing their effectiveness in treating osteoporosis. CD271/CD45 UOPCs were isolated from the endometrial tissue of inbred Balb/c mice through magnetic activated cell sorting. Stem cell differentiation assays were used for CD271/CD45 UOPCs . , the UOPCs were implanted into mouse osteoporosis models through tail-vein injection for 8 weeks. Osteogenic differentiation was examined by X-rays and computed tomography (CT) scans. Enhanced green fluorescent protein (EGFP)-labeled UOPCs, obtained from C57BL/6-Tg (ACTb-EGFP) 1Osb/J mice, were used to assess cell survival in the osteoporosis model. The levels of osteogenic markers were assessed by enzyme-linked immunosorbent assay. , UOPCs were able to form into typical spheres and various differentiations. , implantation of UOPCs into osteoporosis model significantly increased bone mineral densities and bone microstructure parameters. The levels of a biochemical marker of bone metabolism, , increased significantly. However, levels of receptor activator of nuclear factor kappa-B ligand decreased. Immunofluorescence staining of osteoporosis mice injected with green fluorescent protein+ UOPCs showed their survival for up to 7 days. In conclusion, stem cells with osteogenic differentiation potential can be isolated from uterine or endometrial tissue. These UOPCs can stably proliferate and differentiate or , which can inhibit bone resorption and osteoclast marker expression. , UOPCs significantly improved reduction in bone density caused by reduced estrogen levels. Such cell transplantation approach is potentially useful in the treatment of osteoporosis.

摘要

骨质疏松症是一种由骨密度低引起的无声疾病,并伴有骨折。本研究旨在探讨子宫干细胞来源的成骨前体细胞(UOPC)的分化作用,评估其在治疗骨质疏松症方面的有效性。通过磁激活细胞分选从近交系 Balb/c 小鼠的子宫内膜组织中分离出 CD271/CD45 UOPC。采用干细胞分化实验对 CD271/CD45 UOPC 进行鉴定。然后,通过尾静脉注射将 UOPC 植入小鼠骨质疏松模型中,持续 8 周。通过 X 射线和计算机断层扫描(CT)扫描检查成骨分化。使用来自 C57BL/6-Tg(ACTb-EGFP)1Osb/J 小鼠的增强型绿色荧光蛋白(EGFP)标记的 UOPC 来评估骨质疏松模型中的细胞存活情况。通过酶联免疫吸附试验评估成骨标志物的水平。结果表明,UOPC 能够形成典型的球体并进行各种分化。进一步研究表明,将 UOPC 植入骨质疏松模型中可显著增加骨矿物质密度和骨微结构参数。骨代谢生化标志物水平显著升高,而核因子κB 受体激活剂配体的水平降低。对注射了绿色荧光蛋白+UOPC 的骨质疏松症小鼠进行免疫荧光染色显示,其在 7 天内仍存活。综上所述,可从子宫或子宫内膜组织中分离出具有成骨分化潜能的干细胞。这些 UOPC 能够稳定增殖和分化,植入骨质疏松症模型后可抑制骨吸收和破骨细胞标志物的表达。总之,UOPC 显著改善了因雌激素水平降低导致的骨密度降低。这种细胞移植方法可能对骨质疏松症的治疗具有潜在的应用价值。

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