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

IF 4.7 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials 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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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

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464

期刊介绍： ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.