A Novel Cellular Therapy to Treat Pancreatic Pain in Experimental Chronic Pancreatitis Using Human Alpha-1 Antitrypsin Overexpressing Mesenchymal Stromal Cells.
A Novel Cellular Therapy to Treat Pancreatic Pain in Experimental Chronic Pancreatitis Using Human Alpha-1 Antitrypsin Overexpressing Mesenchymal Stromal Cells.
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DOI：
10.3390/biomedicines9111695
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发表时间：
2021-11-16
期刊：
影响因子：
4.7
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Chow RP;Nguyen K;Gou W;Green E;Morgan K;Lancaster W;Helke K;Strange C;Wang H
慢性胰腺炎（CP）的特点是胰腺炎症、纤维化和腹痛，难以治疗。在非肥胖糖尿病小鼠中，过表达人α -1抗胰蛋白酶（hAAT-MSCs）的间充质间质细胞（MSCs）比天然间充质间质间质细胞（MSCs）表现出更好的移动性和保护功能。我们使用三硝基苯磺酸（TNBS）诱导的CP小鼠模型研究hAAT-MSCs是否可以减轻CP及其相关的疼痛。CP小鼠分别给予天然人MSCs或hAAT-MSCs （0.5 × 106个/只，灌胃，n = 6-8个/组）。采用渐进式冯弗雷丝法测定内脏疼痛指数。形态学染色分析胰腺形态及胰腺肥大细胞计数。采用免疫组化方法检测痛觉感受器瞬时受体电位香草样蛋白1 （TRPV1）在背根神经节（DRG）中的表达。haat - msc处理的CP小鼠胰腺形态学和组织学保存最好。MSC或hAAT-MSC输注可减轻腹痛敏感性。hAAT-MSC治疗还能抑制TRPV1在DRG中的表达，降低TNBS诱导的胰腺肥大细胞密度。总体而言，hAAT-MSCs减轻CP疼痛和减轻胰腺炎症与MSCs相同，与MSC组相比，hAAT-MSC组有更高胰腺重量和更好疼痛缓解的趋势。MSCs和hAAT-MSCs都可能作为一种新的治疗cp相关性疼痛的工具。
Chronic pancreatitis (CP) is characterized by pancreatic inflammation, fibrosis, and abdominal pain that is challenging to treat. Mesenchymal stromal cells (MSCs) overexpressing human alpha-1 antitrypsin (hAAT-MSCs) showed improved mobility and protective functions over native MSCs in nonobese diabetic mice. We investigated whether hAAT-MSCs could mitigate CP and its associated pain using trinitrobenzene sulfonic acid (TNBS)-induced CP mouse models. CP mice were given native human MSCs or hAAT-MSCs (0.5 × 106 cells/mouse, i.v., n = 6–8/group). The index of visceral pain was measured by graduated von Frey filaments. Pancreatic morphology and pancreatic mast cell count were analyzed by morphological stains. Nociceptor transient receptor potential vanilloid 1 (TRPV1) expression in dorsal root ganglia (DRG) was determined by immunohistochemistry. hAAT-MSC-treated CP mice best preserved pancreatic morphology and histology. MSC or hAAT-MSC infusion reduced abdominal pain sensitivities. hAAT-MSC therapy also suppressed TRPV1 expression in DRG and reduced pancreatic mast cell density induced by TNBS. Overall, hAAT-MSCs reduced pain and mitigated pancreatic inflammation in CP equal to MSCs with a trend toward a higher pancreatic weight and better pain relief in the hAAT-MSC group compared to the MSC group. Both MSCs and hAAT-MSCs might be used as a novel therapeutic tool for CP-related pain.
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影响因子：
5.2
作者：
Guo, Wei;Wang, Hu;Zou, Shiping;Gu, Ming;Watanabe, Mineo;Wei, Feng;Dubner, Ronald;Huang, George T. -J.;Ren, Ke
通讯作者：
Ren, Ke
影响因子：
3.7
作者：
Demir IE;Schorn S;Schremmer-Danninger E;Wang K;Kehl T;Giese NA;Algül H;Friess H;Ceyhan GO
通讯作者：
Ceyhan GO
DOI：
10.1111/j.1365-2222.2010.03685.x
发表时间：
2011-04
期刊：
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
影响因子：
--
作者：
Brown JM;Nemeth K;Kushnir-Sukhov NM;Metcalfe DD;Mezey E
通讯作者：
Mezey E
DOI：
10.1080/15412550802092936
发表时间：
2008-06-01
影响因子：
2.2
作者：
Aldonyte, Ruta;Hutchinson, Edgar Tarun;Zhang, Jianliang
通讯作者：
Zhang, Jianliang
影响因子：
3.5
作者：
BUCURENCI, N;BLAKE, DR;WINYARD, PG
通讯作者：
WINYARD, PG