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用于治疗干燥综合征所致涎腺炎的牙髓干细胞的应用途径及剂量评估:一项临床前研究

Route of Application and Dose Evaluation of Dental Pulp Stem Cells for the Treatment of Sialadenitis Caused by Sjögren's Syndrome: A Preclinical Study.

作者信息

Du Zhihao, Feng Lifang, Zhang Yu, Peng Xin, Zhang Shan, Zhao Rui, Lei Jia, Li Xiaotong, Yu Guangyan, Ding Chong

机构信息

Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, No. 22, Zhongguancun South Avenue, Haidian District, Beijing 100081, China.

Center Laboratory, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, No. 22, Zhongguancun South Avenue, Haidian District, Beijing 100081, China.

出版信息

Biomedicines. 2025 Apr 28;13(5):1068. doi: 10.3390/biomedicines13051068.

Abstract

Sjögren's syndrome (SS) is an autoimmune disorder characterized by sicca syndrome and/or systemic manifestations. In this study, non-obese diabetic () mice were used as an animal model for studying SS, to evaluate the optimal administration route and dose range of dental pulp stem cells (DPSCs) in the treatment of sialadenitis caused by SS. Different doses of DPSCs were transplanted into the submandibular glands (SMGs) of 14-week-old mice through two different methods: injection or retrograde perfusion through the catheter orifice into the SMG. At 21 weeks of age, the saliva flow rate (SFR), ectopic lymphocytes, and CD4 T-cell infiltration were measured. Tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) in the glandular tissues were also quantitatively detected. Compared with untreated and PBS-injected controls, different-dose groups of the two administration methods showed an increased saliva flow rate of mice to varying degrees, reduced infiltration of lymphocytes and CD4 T cells in the SMG, and decreased IFN-γ/TNF-α levels. Finally, we compared these two administration routes and found that the perfusion of 2 × 10 DPSCs presents good therapeutic effects. DPSC perfusion through the catheter orifice is a simple and effective treatment method, which is worthy of further investigation through clinical trials.

摘要

干燥综合征(SS)是一种以干燥综合征和/或全身表现为特征的自身免疫性疾病。在本研究中,非肥胖糖尿病(NOD)小鼠被用作研究SS的动物模型,以评估牙髓干细胞(DPSCs)治疗SS所致涎腺炎的最佳给药途径和剂量范围。通过两种不同方法将不同剂量的DPSCs移植到14周龄NOD小鼠的下颌下腺(SMG)中:注射或通过导管口逆行灌注到SMG中。在21周龄时,测量唾液流速(SFR)、异位淋巴细胞和CD4 T细胞浸润情况。还定量检测了腺组织中的肿瘤坏死因子-α(TNF-α)和干扰素-γ(IFN-γ)。与未治疗和注射PBS的对照组相比,两种给药方法的不同剂量组均使NOD小鼠的唾液流速不同程度增加,SMG中淋巴细胞和CD4 T细胞浸润减少,IFN-γ/TNF-α水平降低。最后,我们比较了这两种给药途径,发现灌注2×10⁶个DPSCs具有良好的治疗效果。通过导管口进行DPSC灌注是一种简单有效的治疗方法,值得通过临床试验进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4567/12109166/467e62f610cb/biomedicines-13-01068-g001.jpg

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