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17β-雌二醇提高自体骨髓间充质干细胞在兔桡骨骨不连缺损愈合中的应用疗效:兔模型研究

17β-estradiol improves the efficacy of exploited autologous bone marrow-derived mesenchymal stem cells in non-union radial defect healing: A rabbit model.

作者信息

Zamani Mazdeh Delaram, Mirshokraei Pezhman, Emami Mohammadreza, Mirshahi Ali, Karimi Iraj

机构信息

Department of Clinical Sciences, School of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.

Department of Clinical Sciences, School of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran; Center of Excellence in Ruminant Abortion and Neonatal Mortality, School of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.

出版信息

Res Vet Sci. 2018 Jun;118:11-18. doi: 10.1016/j.rvsc.2017.12.024. Epub 2017 Dec 28.

DOI:10.1016/j.rvsc.2017.12.024
PMID:29334646
Abstract

Exploiting mesenchymal stem cells (MSCs) appears to be an appealing alternative to the traditional clinical approach in the treatment of non-union bone defects. It has been shown that 17β-estradiol improves the osteogenesis and proliferation potential of the MSCs via estrogen receptors. We investigated the effect of 17β-estradiol on exploiting autologous BMSCs (bone marrow-derived MSCs) for the purpose of healing of radial non-union segmental defect in rabbit. Twenty rabbits were divided into 4 experimental groups: 1. Control group; 2. MSC treatment group; 3. 17β-estradiol (E2) treatment group; and 4. E2+MSC treatment group. Isolated BMSCs were seeded in a critical-sized defect on radial mid-diaphysis that was filled with autologous fibrin clot differently in 4 groups: 1. intact fibrin clot (control); 2. Fibrin clot containing MSCs; 3. Estradiol; and 4. E and MSCs. Defect healing was assessed by radiological (week 0, 2, 4, 6, 8 and 10) and histopathological evaluation (week 10). Radiological evaluation data demonstrated that quantities for the E2+MSC group were significantly the greatest in comparison with the other groups at week 4 to 10 inclusive. Moreover, Histopathological evaluation indicated that the E2+MSC group had the highest score which was significantly greater than the E2 group and the control group (P<0.05). In-vivo application of in situ 17β-estradiol provides the seeded BMSCs with improved osteogenic capacity in tandem with an accelerated rate of bone healing. This obviously more qualified approach that yields in a shorter time appears to be promising for the future cell-based clinical treatments of the non-union bone fractures. Exploiting mesenchymal stem cells (MSCs) appears to be an appealing alternative to the traditional clinical approach in the treatment of non-union bone defects. It has been shown that 17β-estradiol improves the osteogenesis and proliferation potential of the MSCs via estrogen receptors. We investigated the effect of 17β-estradiol on exploiting autologous BMSCs (bone marrow-derived MSCs) for the purpose of healing of radial non-union segmental defect in rabbit. Twenty rabbits were divided into 4 experimental groups: 1. Control group; 2. MSC treatment group; 3. 17β-estradiol (E2) treatment group; and 4. E2+MSC treatment group. Isolated BMSCs were seeded in a critical-sized defect on the radial mid-diaphysis that was filled with autologous fibrin clot differently in 4 groups: 1. intact fibrin clot (control); 2. Fibrin clot containing MSCs; 3. Estradiol; and 4. E and MSCs. Defect healing was assessed by radiological (week 0, 2, 4, 6, 8 and 10) and histopathological evaluation (week 10). Radiological evaluation data demonstrated that quantities for the E2+MSC group were significantly the greatest in comparison with the other groups at week 4 to 10 inclusive. Moreover, Histopathological evaluation indicated that the E2+MSC group had the highest score which was significantly greater than the E2 group and the control group (P<0.05). In-vivo application of in situ 17β-estradiol provides the seeded BMSCs with improved osteogenic capacity in tandem with an accelerated rate of bone healing. This obviously more efficient approach that yields in a shorter time appears to be promising for future cell-based clinical treatments of the non-union bone fractures.

摘要

在治疗骨不连缺损方面,利用间充质干细胞(MSCs)似乎是一种比传统临床方法更具吸引力的替代方案。研究表明,17β-雌二醇可通过雌激素受体提高MSCs的成骨能力和增殖潜力。我们研究了17β-雌二醇对利用自体骨髓间充质干细胞(BMSCs)修复兔桡骨节段性骨不连缺损的影响。将20只兔子分为4个实验组:1. 对照组;2. MSC治疗组;3. 17β-雌二醇(E2)治疗组;4. E2+MSC治疗组。将分离的BMSCs接种到桡骨干中段的临界大小缺损处,4组缺损处填充的自体纤维蛋白凝块不同:1. 完整纤维蛋白凝块(对照组);2. 含MSCs的纤维蛋白凝块;3. 雌二醇;4. 雌二醇和MSCs。通过放射学评估(第0、2、4、6、8和10周)和组织病理学评估(第10周)来评估缺损愈合情况。放射学评估数据表明,在第4至10周(含第4周和第10周),E2+MSC组的各项指标与其他组相比显著最高。此外,组织病理学评估表明,E2+MSC组得分最高,显著高于E2组和对照组(P<0.05)。原位应用17β-雌二醇可使接种的BMSCs成骨能力增强,同时加快骨愈合速度。这种明显更有效的方法能在更短时间内取得效果,似乎对未来基于细胞的骨不连骨折临床治疗很有前景。在治疗骨不连缺损方面,利用间充质干细胞(MSCs)似乎是一种比传统临床方法更具吸引力的替代方案。研究表明,17β-雌二醇可通过雌激素受体提高MSCs的成骨能力和增殖潜力。我们研究了17β-雌二醇对利用自体骨髓间充质干细胞(BMSCs)修复兔桡骨节段性骨不连缺损的影响。将20只兔子分为4个实验组:1. 对照组;2. MSC治疗组;3. 17β-雌二醇(E2)治疗组;4. E2+MSC治疗组。将分离的BMSCs接种到桡骨干中段的临界大小缺损处,4组缺损处填充的自体纤维蛋白凝块不同:1. 完整纤维蛋白凝块(对照组);2. 含MSCs的纤维蛋白凝块;3. 雌二醇;4. 雌二醇和MSCs。通过放射学评估(第0、2、4、6、8和10周)和组织病理学评估(第10周)来评估缺损愈合情况。放射学评估数据表明,在第4至10周(含第4周和第10周),E2+MSC组的各项指标与其他组相比显著最高。此外,组织病理学评估表明,E2+MSC组得分最高,显著高于E2组和对照组(P<0.05)。原位应用17β-雌二醇可使接种的BMSCs成骨能力增强,同时加快骨愈合速度。这种明显更有效的方法能在更短时间内取得效果,似乎对未来基于细胞的骨不连骨折临床治疗很有前景。

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