Sun Xiaoli, Gao Yang, Chen Haoyuan, Yang Ningning, Zhang Yichi, Liu Qi, Jiang Yanan, Jin Shizhu
Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, Harbin Medical University Harbin 150086, P. R. China.
Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University Harbin 150081, P. R. China.
Am J Transl Res. 2021 Mar 15;13(3):1389-1399. eCollection 2021.
Acute pancreatitis (AP) is commonly accompanied by intense pain and is associated with high mortality rates. However, the effectiveness of existing therapeutic approaches remains unsatisfactory. Stem cell therapy, which can promote the regeneration of damaged tissue and alleviate systemic inflammatory responses, has brought new possibility for patients suffering from AP. In particular, hair follicle-derived mesenchymal stem cells (HF-MSCs) are proposed as a suitable cell source for treating pancreatic diseases, but further research on their effectiveness, safety, and underlying mechanisms is warranted for clinical implementation. In this work, the therapeutic potential of HF-MSC transplantation was studied in an L-arginine-induced AP rat model. HF-MSCs were extracted from infant Sprague-Dawley (SD) rats, expanded , and detected by flow cytometry. HF-MSCs were labeled by PKH67 and transplanted into rats with AP via tail vein injection. Serum specimens were collected at 24 h, 48 h, and 72 h after transplantation, and the levels of amylase, lipase, and anti-inflammatory factors, namely interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), were analyzed. Pancreas samples were collected and assayed by immunofluorescence and immunohistochemistry 1 week after transplantation to monitor the differentiation of HF-MSCs and the functional recovery of the damaged pancreas. Intravenously delivered rat HF-MSCs spontaneously homed to the damaged pancreas and expressed pancreatic progenitor cell markers, relieved inflammation, and boosted pancreatic regeneration. These findings indicate that HF-MSC transplantation is a potentially effective treatment for AP.
急性胰腺炎(AP)通常伴有剧烈疼痛,且死亡率较高。然而,现有治疗方法的效果仍不尽人意。干细胞疗法能够促进受损组织的再生并减轻全身炎症反应,为AP患者带来了新的希望。特别是,毛囊来源的间充质干细胞(HF-MSCs)被认为是治疗胰腺疾病的合适细胞来源,但在其有效性、安全性及潜在机制方面仍需进一步研究以用于临床实践。在本研究中,我们在L-精氨酸诱导的AP大鼠模型中研究了HF-MSC移植的治疗潜力。从幼年Sprague-Dawley(SD)大鼠中提取HF-MSCs,进行扩增,并通过流式细胞术进行检测。用PKH67标记HF-MSCs,经尾静脉注射将其移植到AP大鼠体内。在移植后24小时、48小时和72小时采集血清样本,分析淀粉酶、脂肪酶以及抗炎因子白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的水平。移植1周后收集胰腺样本,通过免疫荧光和免疫组织化学进行检测,以监测HF-MSCs的分化情况以及受损胰腺的功能恢复情况。静脉注射的大鼠HF-MSCs可自发归巢至受损胰腺,表达胰腺祖细胞标志物,减轻炎症,并促进胰腺再生。这些研究结果表明,HF-MSC移植是一种治疗AP的潜在有效方法。