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牙龈来源间充质干细胞治疗再生受辐射唾液腺:小鼠模型中的功能与组织学证据

英文原题:Gingival-derived mesenchymal stem cell therapy regenerated the radiated salivary glands: functional and histological evidence in murine model.

PubMed 2024/02/16(内容时间) Stem Cell Res Ther Q1 · IF 7.8(JCR 2025)

研究概要

该研究通过使用GMSCs对受辐射的SG进行重编程,为治疗口干症提供了一种新的潜在治疗策略。

研究思路结论见上方概要

头颈部肿瘤管理中的放疗会导致唾液腺(SG)退化。本研究旨在利用小鼠模型,确定牙龈间充质干细胞(GMSCs)作为基于细胞的疗法,再生受照射的腮腺SG组织并恢复其功能的潜力。

从4只健康豚鼠的牙龈组织中分离培养的细胞,取第3代,通过流式细胞术检测表面标志物及多向分化能力,鉴定为GMSCSs。将21只豚鼠等分为三组:I组/试验组,接受头颈部单次局部照射15 Gy后静脉注射标记的GMSCs;II组/阳性对照组,接受相同照射剂量后注射磷酸盐缓冲液(PBS);III组/阴性对照组,仅注射PBS。在基线、照射后11天、8周、13周和16周测量体重和唾液流率(SFR)。在第16周,采集腮腺以评估腺体重量并进行组织学和免疫组织化学分析。

注射的GMSCs归巢至退化的腺体,随后正常腺体组织学腺泡和管状结构得以恢复,并伴有细胞增殖显著增加和凋亡活性降低。随后,与未治疗的照射组相比,观察到体重和SFR显著增加,以及在第16周时腺体重量增加。

展开英文摘要原文

BACKGROUND: Radiotherapy in head and neck cancer management causes degeneration of the salivary glands (SG). This study was designed to determine the potential of gingival mesenchymal stem cells (GMSCs) as a cell-based therapy to regenerate irradiated parotid SG tissues and restore their function using a murine model. METHODS: Cultured isolated cells from gingival tissues of 4 healthy guinea pigs at passage 3 were characterized as GMSCSs using flow cytometry for surface markers and multilineage differentiation capacity. Twenty-one Guinea pigs were equally divided into three groups: Group I/Test, received single local irradiation of 15 Gy to the head and neck field followed by intravenous injection of labeled GMSCs, Group II/Positive control, which received the same irradiation dose followed by injection of phosphate buffer solution (PBS), and Group III/Negative control, received (PBS) injection only. Body weight and salivary flow rate (SFR) were measured at baseline, 11 days, 8-, 13- and 16-weeks post-irradiation. At 16 weeks, parotid glands were harvested for assessment of gland weight and histological and immunohistochemical analysis. RESULTS: The injected GMSCs homed to degenerated glands, with subsequent restoration of the normal gland histological acinar and tubular structure associated with a significant increase in cell proliferation and reduction in apoptotic activity. Subsequently, a significant increase in body weight and SFR, as well as an increase in gland weight at 16 weeks in comparison with the irradiated non-treated group were observed. CONCLUSION: The study provided a new potential therapeutic strategy for the treatment of xerostomia by re-engineering radiated SG using GMSCs.

论文信息

作者
Zayed HM、Kheir El Din NH、Abu-Seida AM、Abo Zeid AA、Ezzatt OM
第一作者单位
Department of Oral Medicine, Periodontology and Oral Diagnosis, Faculty of Dentistry, Ain Shams University, 20 Organization of African Union St., Cairo, 1156, Egypt.Egypt
通讯作者单位
Department of Oral Medicine, Periodontology and Oral Diagnosis, Faculty of Dentistry, Ain Shams University, 20 Organization of African Union St., Cairo, 1156, Egypt. dr.ola@dent.asu.edu.eg.Egypt
期刊
Stem cell research & therapy2024 Feb 16
原文标识
PubMed 38365799 · DOI 10.1186/s13287-024-03659-7