Bone Marrow-Derived Stem Cell (BMDSC) transplantation improves fertility in a murine model of Asherman's syndrome.

Bone Marrow-Derived Stem Cell (BMDSC) transplantation improves fertility in a murine model of Asherman's syndrome.
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DOI:
10.1371/journal.pone.0096662
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Taylor HS
Taylor HS
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Alawadhi F;Du H;Cakmak H;Taylor HS

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Asherman综合征的特征在于子宫内膜基底层损伤导致的子宫内粘连或纤维化,并且与由于正常子宫内膜损失导致的不孕症相关。我们以前已经表明,骨髓来源的干细胞(BMDSCs)植入子宫内膜在小鼠和人类和子宫缺血/再灌注损伤促进BMDSCs迁移到子宫内膜,然而,BMDSCs在Asherman综合征的作用还没有得到表征。在这里,通过创伤子宫来创建Asherman综合征的小鼠模型。我们评估了Asherman综合征模型中BMDSCs移植后干细胞募集和妊娠情况。在Asheman综合征模型中,BMDSC移植后,携带Y染色体的CD 45-细胞占总子宫内膜细胞的不到0.1%。与未受伤的对照组相比,在受损子宫中发现的Y+ CD 45-细胞数量是未受伤对照组的两倍。在单角损伤的小鼠中,损伤和未损伤的子宫角之间没有显著差异。在BMDSC移植组中,10只小鼠中有9只受孕,而非移植组中只有3只受孕(卡方检验p = 0.0225);未受伤对照组中的所有小鼠都受孕。  组间的受孕时间和平均窝仔数无差异。总之,BMDSC响应于损伤而被募集到子宫内膜。在Asherman综合征小鼠中,BMDSC移植后生育力提高,证明了这些细胞在子宫修复中的功能作用。BMDSC移植是一种潜在的治疗Asherman综合征的新方法,也可能有助于预防子宫损伤后的Asherman综合征。
Asherman's Syndrome is characterized by intrauterine adhesions or fibrosis resulting as a consequence of damage to the basal layer of endometrium and is associated with infertility due to loss of normal endometrium. We have previously shown that bone marrow derived stem cells (BMDSCs) engraft the endometrium in mice and humans and Ischemia/reperfusion injury of uterus promoted BMDSCs migration to the endometrium; however, the role of BMDSCs in Asherman's syndrome has not been characterized. Here a murine model of Asherman's syndrome was created by traumatizing the uterus. We evaluate stem cell recruitment and pregnancy after BMDSCs transplantation in a model of Asherman's syndrome. In the Asheman's syndrome model, after BMDSC transplant, the Y chromosome bearing CD45-cells represented less than 0.1% of total endometrial cells. Twice the number of Y+CD45- cells was identified in the damaged uterus compared to the uninjured controls. There was no significant difference between the damaged and undamaged uterine horns in mice that received injury to a single horn. In the BMDSC transplant group, 9 of the 10 mice conceived, while only 3 of 10 in the non-transplanted group conceived (Chi-Square p = 0.0225); all mice in an uninjured control group conceived. The time to conception and mean litter size were not different between groups. Taken together, BMDSCs are recruited to endometrium in response to injury. Fertility improves after BMDSC transplant in Asherman's Syndrome mice, demonstrating a functional role for these cells in uterine repair. BMDSC transplantation is a potential novel treatment for Asherman's Syndrome and may also be useful to prevent Asherman's syndrome after uterine injury.
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