Comparison the therapeutic effects of bone marrow CD144⁺ endothelial cells and CD146⁺ mesenchymal stem cells in POF rats.

IF 2.2 4区工程技术 Q3 PHARMACOLOGY & PHARMACY

Bioimpacts Pub Date : 2023-01-01 Epub Date: 2023-07-29 DOI:10.34172/bi.2023.27781

Nahideh Nazdikbin Yamchi, Farhad Amjadi, Rahim Beheshti, Mehdi Hassanpour, Reza Shirazi, Amin Tamadon, Reza Rahbarghazi, Mahdi Mahdipour

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引用次数: 0

Abstract

Introduction: Premature ovarian insufficiency (POI) is a challenging issue in terms of reproduction biology. In this study, therapeutic properties of bone marrow CD146⁺ mesenchymal stem cells (MSCs) and CD144⁺ endothelial cells (ECs) were separately investigated in rats with POI.

Methods: POI rats were classified into control POI, POI + CD146⁺ MSCs, and POI + CD144⁺ ECs groups. Enriched CD146⁺ MSCs and CD144⁺ ECs were directly injected into ovarian tissue (15 × 10⁴ cells/10 μL) in relevant groups. After 4 weeks, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E₂) levels were measured in blood samples. Ovarian tissues were collected and subjected to Hematoxylin-Eosin and Masson's trichrome staining. The expression of angp-2, vegfr-2, smad-2, -4, -6, and tgf-β1 was studied using qRT-PCR analysis. Histopathological examination indicated an increased pattern of atretic follicles in the POI group related to the control rats (P<0.0001).

Results: Data indicated that injection of POI + CD146⁺ MSCs and CD144⁺ ECs in POI rats reduced atretic follicles and increased the number of normal follicles (P<0.01). Along with these changes, the content of blue-colored collagen fibers was diminished after cell transplantation. Besides, cell transplantation in POI rats had the potential to reduce increased FSH, and LH levels (P<0.05). In contrast, E2 content was increased in POI + CD146⁺ MSCs and POI + CD144⁺ ECs groups compared to control POI rats, indicating restoration of follicular function. CD144⁺ (smad-2, and -4) and CD146⁺ (smad-6) cells altered the activity of genes belonging TGF-β signaling pathway. Unlike POI + CD146⁺ MSCs, aberrant angiogenesis properties were significantly down-regulated in POI + CD144⁺ ECs related to the control POI group (P<0.05).

Conclusion: The transplantation of bone marrow CD146⁺ and CD144⁺ cells can lead to the restoration of ovarian tissue function in POI rats via modulating different mechanisms associated with angiogenesis and fibrosis.

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骨髓CD144+内皮细胞与CD146+间充质干细胞治疗POF大鼠的疗效比较

引言：卵巢早衰（POI）在生殖生物学方面是一个具有挑战性的问题。在本研究中，分别研究了骨髓CD146+间充质干细胞（MSC）和CD144+内皮细胞（EC）在POI大鼠中的治疗特性。方法：将POI大鼠分为对照组、POI+CD146+MSCs组和POI+CD144+ECs组。将富集的CD146+MSCs和CD144+EC直接注射到相关组的卵巢组织中（15×104个细胞/10μL）。4周后，测量血液样本中的卵泡刺激素（FSH）、黄体生成素（LH）和雌二醇（E2）水平。收集卵巢组织并进行苏木精-曙红和Masson三色染色。应用qRT-PCR分析研究angp-2、vegfr-2、smad-2、-4、-6和tgf-β1的表达。组织病理学检查显示，与对照组大鼠相比，POI组闭锁卵泡数量增加（P＜0.0001）。结果：POI大鼠注射POI+CD146+MSCs和CD144+ECs可减少闭锁卵泡数量，增加正常卵泡数量（P＜0.01），细胞移植后，蓝色胶原纤维的含量减少。此外，POI大鼠的细胞移植有可能降低FSH和LH水平的增加（P<0.05）。相反，与对照组相比，POI+CD146+MSCs和POI+CD144+ECs组的E2含量增加，表明卵泡功能恢复。CD144+（smad-2和-4）和CD146+（smad-6）细胞改变了TGF-β信号通路基因的活性。与POI+CD146+MSCs不同，与对照组相关的POI+CD144+ECs异常血管生成特性显著下调（P<0.05）。结论：骨髓CD146+和CD144+细胞移植可通过调节与血管生成和纤维化相关的不同机制，导致POI大鼠卵巢组织功能的恢复

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来源期刊

Bioimpacts Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

CiteScore

4.80

自引率

7.70%

发文量

审稿时长

5 weeks

期刊介绍： BioImpacts (BI) is a peer-reviewed multidisciplinary international journal, covering original research articles, reviews, commentaries, hypotheses, methodologies, and visions/reflections dealing with all aspects of biological and biomedical researches at molecular, cellular, functional and translational dimensions.