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）的有益作用。

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

作者信息

Cai Junhong, Liang Xiaochen, Sun Yuting, Bao Shan

机构信息

Medical Laboratory Central, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570311, PR China.

Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan 571199, PR China; Key Laboratory of Reproductive Health Diseases Research and Translation (Hainan Medical University), Ministry of Education, Haikou, Hainan 571199, PR China.

出版信息

Transpl Immunol. 2024 Jun;84:102051. doi: 10.1016/j.trim.2024.102051. Epub 2024 May 12.

DOI:10.1016/j.trim.2024.102051

PMID:38744348

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.

摘要

背景

卵巢早衰（POF），也称为原发性卵巢功能不全，是年轻女性常见的内分泌疾病。利用干细胞的再生医学的出现可能改善卵巢功能和结构，为POF治疗带来了有前景的希望。在本研究中，我们探讨了人脐带间充质干细胞（HUCMSC）移植对环磷酰胺（CTX）诱导的藏猪POF模型的治疗效果。

方法

我们培养并鉴定了HUCMSC，用DiR碘化物红色染料标记它们，并将其植入CTX诱导的藏猪POF模型中。记录每日体重变化，并在第0、7和14天测量雌二醇（E2）和促卵泡激素（FSH）水平。在21天观察期结束时，对双侧卵巢进行体内成像，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缺口末端标记法评估细胞凋亡，并用免疫组织化学法测定p-AKT、p-ERK1/2、BAX和BCL2的表达水平。

结果

我们的分析表明HUCMSC成功递送至POF猪模型的卵巢。观察到体重、E2水平、卵巢指数和正常卵泡数量显著增加（均p<0.05）。此外，HUCMSC移植后FSH水平降低，卵巢组织形态改善（均p<0.05）。重要的是，观察到p-AKT、p-ERK1/2和BCL2表达上调，而BAX表达受到抑制（均p<0.05），表明卵巢细胞凋亡受到抑制。