Effects of TGF-β3 on meniscus repair using human amniotic epithelial cells.

IF 2.8 3区医学 Q1 ORTHOPEDICS Journal of Orthopaedic Surgery and Research Pub Date : 2025-03-10 DOI:10.1186/s13018-025-05640-3

Yupeng He, Ya Li, Xiaodong Zhi, Yuqiang Zhang, Wei Wang

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引用次数: 0

Abstract

Background: Meniscus injury is one of the most common knee diseases, which is managed through conservative and surgical treatments. In recent years, biotherapy has shown great potential to treat various symptoms caused by meniscus injury repair. Human amniotic epithelial cells (hAECs), which are easy to acquire, non-tumorigenic, and high tri-lineage differentiation potential, are a promising cell source for biotherapy and tissue engineering applications. Studies have demonstrated that the Transforming Growth Factor-β3 (TGF-β3) can facilitate chondrocyte differentiation and maturation.

Methods: Both in vitro test and in vivo test were employed. In the in vitro test, human amniotic epithelial cells (hAECs), human amniotic mesenchymal stem cells (hAMCs), and fibrochondrocytes (FCs) were extracted and identified by flow cytometry and immunohistochemistry (IHC). These cells were treated with TGF-β3 for one week, followed by IHC staining and qPCR to explore TGF-β3-induced fibrocartilage formation in hAECs. In the in vivo tests, a meniscus injury model was established based on rabbits, and the Sham, the control (normal saline), and the hAECs + TGF-β3 groups were used. Additionally, the meniscus was collected and checked through general examination and IHC analysis 90 d after surgery.

Results: Routine transcriptome analysis confirmed that TGF-β3 induced the differentiation of amniotic epithelial cells (hAECs) into fibrochondrocytes through the Wnt signaling pathway. This finding was corroborated using Western blot (WB) and quantitative PCR (QPCR). Among the five experimental groups, the highest expression of target proteins and genes was detected in hAECs + TGF-β3 group, followed by the hAECs + hAMCs + TGF-β3 group, the hAMCs + TGF-β3 group, the hAECs + FCs group, and the FCs group. The observed differences were statistically significant (P < 0.05). In vivo, treatment with hAECs + TGF-β3 facilitated effective repair of damaged menisci.

Conclusions: hAECs + TGF-β3 can potentially promote the healing of meniscus injuries, laying the foundation for further research to promote its clinical translation.

Trial registration: Not applicable.

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利用人体羊膜上皮细胞研究 TGF-β3 对半月板修复的影响。

背景：半月板损伤是最常见的膝关节疾病之一，可通过保守和手术治疗。近年来，生物疗法在治疗半月板损伤修复引起的各种症状方面显示出巨大的潜力。人羊膜上皮细胞（hAECs）具有易获得、非致瘤性和高三系分化潜力的特点，是生物治疗和组织工程应用中很有前途的细胞来源。研究表明，转化生长因子-β3 （TGF-β3）可以促进软骨细胞分化和成熟。方法：采用体外试验和体内试验相结合的方法。体外实验提取人羊膜上皮细胞（hAECs）、人羊膜间充质干细胞（hAMCs）和纤维软骨细胞（FCs），采用流式细胞术和免疫组化（IHC）进行鉴定。TGF-β3作用1周后，采用免疫组化（IHC）染色和qPCR检测TGF-β3诱导的hAECs纤维软骨形成。在体内实验中，以家兔为模型建立半月板损伤模型，采用Sham组、对照组（生理盐水）和hAECs + TGF-β3组。术后90 d采集半月板，进行全身检查和免疫组化分析。结果：常规转录组分析证实TGF-β3通过Wnt信号通路诱导羊膜上皮细胞（hAECs）向纤维软骨细胞分化。Western blot （WB）和QPCR （QPCR）证实了这一发现。5个实验组中，hAECs + TGF-β3组靶蛋白和基因表达量最高，其次为hAECs + hAMCs + TGF-β3组、hAECs + TGF-β3组、hAECs + FCs组和FCs组。结论：hAECs + TGF-β3具有潜在的促进半月板损伤愈合的作用，为进一步研究促进其临床转化奠定基础。试验注册：不适用。

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来源期刊

Journal of Orthopaedic Surgery and Research ORTHOPEDICS-

CiteScore

4.10

自引率

7.70%

发文量

494

审稿时长

>12 weeks

期刊介绍： Journal of Orthopaedic Surgery and Research is an open access journal that encompasses all aspects of clinical and basic research studies related to musculoskeletal issues. Orthopaedic research is conducted at clinical and basic science levels. With the advancement of new technologies and the increasing expectation and demand from doctors and patients, we are witnessing an enormous growth in clinical orthopaedic research, particularly in the fields of traumatology, spinal surgery, joint replacement, sports medicine, musculoskeletal tumour management, hand microsurgery, foot and ankle surgery, paediatric orthopaedic, and orthopaedic rehabilitation. The involvement of basic science ranges from molecular, cellular, structural and functional perspectives to tissue engineering, gait analysis, automation and robotic surgery. Implant and biomaterial designs are new disciplines that complement clinical applications. JOSR encourages the publication of multidisciplinary research with collaboration amongst clinicians and scientists from different disciplines, which will be the trend in the coming decades.