Beneficial effects of human umbilical cord mesenchymal stem cell (HUCMSC) transplantation on cyclophosphamide (CTX)-induced premature ovarian failure (POF) in Tibetan miniature pigs

IF 1.6 4区 医学 Q4 IMMUNOLOGY Transplant immunology Pub Date : 2024-05-12 DOI:10.1016/j.trim.2024.102051
Junhong Cai , Xiaochen Liang , Yuting Sun , Shan Bao
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Abstract

Background

Premature ovarian failure (POF), also known as primary ovarian insufficiency, is a common endocrine disease in young women. The emergence of regenerative medicine using stem cells may improve ovarian function and structure, and represents a promising prospect for POF treatment. In his study, we explored the therapeutic effects of human umbilical cord mesenchymal stem cell (HUCMSC) transplantation in a Tibetan miniature pig model of cyclophosphamide (CTX)-induced POF.

Methods

We cultured and identified HUCMSCs, labeled them with DiR iodide red dye, and implanted them into a CTX-induced model of POF in Tibetan miniature pigs. The daily weight changes were recorded, and the levels of estradiol (E2) and follicle-stimulating hormone (FSH) were measured on days 0, 7, and 14. At the end of the 21-day observation period, in vivo imaging of the bilateral ovaries was performed, and the ovarian index was measured. Ovarian tissue morphology and follicles were examined by hematoxylin-eosin staining. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay was employed to assess cell apoptosis, and immunohistochemistry was used to determine the levels of p-AKT, p-ERK1/2, BAX, and BCL2 expression.

Results

Our analysis indicated successful delivery of HUCMSCs to the ovaries of the POF pig model. Significant increases were observed in body weight, E2 levels, ovarian index, and number of normal follicles (all p < 0.05). Moreover, FSH levels reduced and ovarian tissue morphology improved following HUCMSCs transplantation (all p < 0.05). Importantly, upregulated p-AKT, p-ERK1/2, and BCL2 expression were observed, whereas the expression of BAX was suppressed (all p < 0.05), suggesting the inhibition of ovarian cell apoptosis.

Conclusion

Our study highlights the significant therapeutic effects of HUCMSC transplantation on CTX-induced POF in a Tibetan miniature pig model.

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人脐带间充质干细胞(HUCMSC)移植对环磷酰胺(CTX)诱导的西藏小型猪卵巢早衰(POF)的有益影响。
背景:卵巢早衰(POF)又称原发性卵巢功能不全,是年轻女性常见的内分泌疾病。干细胞再生医学的出现可改善卵巢功能和结构,为治疗卵巢早衰带来了广阔前景。在这项研究中,我们探讨了人脐带间充质干细胞(HUCMSC)移植在环磷酰胺(CTX)诱导的POF西藏小型猪模型中的治疗效果:我们培养并鉴定了HUCMSCs,用DiR碘化红染料标记了它们,并将其植入CTX诱导的POF模型藏系小型猪体内。记录每天的体重变化,并在第0天、第7天和第14天测量雌二醇(E2)和促卵泡激素(FSH)的水平。在 21 天观察期结束时,对双侧卵巢进行活体成像,并测量卵巢指数。通过苏木精-伊红染色检查卵巢组织形态和卵泡。采用末端脱氧核苷酸转移酶介导的 dUTP nick-end 标记检测法评估细胞凋亡,免疫组化法测定 p-AKT、p-ERK1/2、BAX 和 BCL2 的表达水平:结果:我们的分析表明,向 POF 猪模型的卵巢成功输送了 HUCMSCs。体重、E2 水平、卵巢指数和正常卵泡数量均有显著增加(均为 p 结论:我们的研究强调了 HUCMSCs 对 POF 猪卵巢的显著治疗作用:我们的研究强调了 HUCMSC 移植对藏香猪模型中 CTX 诱导的 POF 的显著治疗效果。
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来源期刊
Transplant immunology
Transplant immunology 医学-免疫学
CiteScore
2.10
自引率
13.30%
发文量
198
审稿时长
48 days
期刊介绍: Transplant Immunology will publish up-to-date information on all aspects of the broad field it encompasses. The journal will be directed at (basic) scientists, tissue typers, transplant physicians and surgeons, and research and data on all immunological aspects of organ-, tissue- and (haematopoietic) stem cell transplantation are of potential interest to the readers of Transplant Immunology. Original papers, Review articles and Hypotheses will be considered for publication and submitted manuscripts will be rapidly peer-reviewed and published. They will be judged on the basis of scientific merit, originality, timeliness and quality.
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