间充质干细胞治疗急性胰腺炎的机制及研究进展

doi:10.11958/20242422

天津医药 ›› 2025, Vol. 53 ›› Issue (3): 331-336.doi: 10.11958/20242422

• 综述 • 上一篇

间充质干细胞治疗急性胰腺炎的机制及研究进展

范慧娟¹^,²(), 刘涛涛², 李楠¹^,², 夏时海²^,^△()

1 天津中医药大学研究生院（邮编301617）
2 中国人民武装警察部队特色医学中心消化内科（消化疾病研究所），天津市肝脏胰腺纤维化与分子诊疗重点实验室

收稿日期:2024-12-30 修回日期:2025-02-17 出版日期:2025-03-15 发布日期:2025-03-31
通讯作者: △E-mail：xshhcx@sina.com
作者简介:范慧娟（1999），女，硕士在读，主要从事消化系统疾病方面研究。E-mail：fanhuijuan0320@163.com
基金资助:
天津市卫生健康科技项目(TJWJ2023QN100)

Mechanism and research progress of mesenchymal stem cell therapy for acute pancreatitis

FAN Huijuan¹^,²(), LIU Taotao², LI Nan¹^,², XIA Shihai²^,^△()

1 Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
2 Department of Gastroenterology (Institute of Digestive diseases), Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin Key Laboratory of Hepatopancreatic Fiberosis and Molecular Diagnosis & Treatment

Received:2024-12-30 Revised:2025-02-17 Published:2025-03-15 Online:2025-03-31
Contact: △E-mail：xshhcx@sina.com

范慧娟, 刘涛涛, 李楠, 夏时海. 间充质干细胞治疗急性胰腺炎的机制及研究进展[J]. 天津医药, 2025, 53(3): 331-336.

FAN Huijuan, LIU Taotao, LI Nan, XIA Shihai. Mechanism and research progress of mesenchymal stem cell therapy for acute pancreatitis[J]. Tianjin Medical Journal, 2025, 53(3): 331-336.

摘要/Abstract

摘要：

急性胰腺炎（AP）是一种自身消化性疾病，且可伴随全身炎症反应及多器官功能衰竭，间充质干细胞（MSCs）已用于AP治疗中并展现出良好的应用潜力，其可通过归巢至损伤部位、抗炎及免疫调节、抗氧化应激、抗凋亡及抗自噬等机制，有效减轻胰腺炎症并促进组织修复。此外，MSCs还可改善AP引起的肺、肠及心脏等多器官损伤。MSCs治疗AP的研究仍停留在动物实验阶段，临床研究较少。该文综述了MSCs治疗AP的相关机制及研究进展，以为其基础研究及临床应用提供参考。

关键词: 间质干细胞, 急性病, 胰腺炎, 重症急性胰腺炎

Abstract:

Acute pancreatitis (AP) is an autopeptic disease, which can be accompanied by systemic inflammation and multiple organ failure. Mesenchymal stem cells (MSCs) have been used in the treatment of AP and have shown good application potential. MSCs can act through multiple mechanisms to reduce pancreatic inflammation and enhance tissue repair. These mechanisms include homing to injury sites, anti-inflammatory and immunomodulatory effects, oxidative stress reduction, inhibition of apoptosis and suppression of autophagy. Additionally, MSCs can mitigate multi-organ damage associated with AP, impacting lungs, intestines, heart and other organs. Research on the application of MSCs in treating AP is predominantly at the preclinical animal study stage, with limited clinical investigations reported. This article reviews the mechanisms and research progress of MSCs in the treatment of AP, aiming to provide references for basic research and clinical applications.

Key words: mesenchymal stem cells, acute disease, pancreatitis, severe acute pancreatitis

中图分类号:

R576

参考文献 47

[1]	LEE P J, PAPACHRISTOU G I. New insights into acute pancreatitis[J]. Nat Rev Gastroenterol Hepatol, 2019, 16(8):479-496. doi:10.1038/s41575-019-0158-2.
[2]	MEDEROS M A, REBER H A, GIRGIS M D. Acute pancreatitis:a review[J]. JAMA, 2021, 325(4):382-390. doi:10.1001/jama.2020.20317.
[3]	TRIKUDANATHAN G, YAZICI C, EVANS PHILLIPS A, et al. Diagnosis and management of acute pancreatitis[J]. Gastroenterology, 2024, 167(4):673-688. doi:10.1053/j.gastro.2024.02.052.
[4]	KAWAKUBO K, OHNISHI S, KUWATANI M, et al. Mesenchymal stem cell therapy for acute and chronic pancreatitis[J]. J Gastroenterol, 2018, 53(1):1-5. doi:10.1007/s00535-017-1363-9.
[5]	聂进, 刘代顺, 张建勇, 等. 脐带间充质干细胞外泌体对慢性阻塞性肺疾病大鼠肺部炎症的作用机制探讨[J]. 天津医药, 2023, 51(12):1326-1331.
	NIE J, LIU D S, ZHANG J Y, et al. The effect and mechanism of exosomes from umbilical cord mesenchymal stem cells on pulmonary inflammation in chronic obstructive pulmonary disease rats[J]. Tianjin Med J, 2023, 51(12):1326-1331. doi:10.11958/20230708.
[6]	MA C, HAN L, WU J, et al. MSCs cell fates in murine acute liver injury and chronic liver fibrosis induced by carbon tetrachloride[J]. Drug Metab Dispos, 2022, 50(10):DMD-AR-2022-000958. doi:10.1124/dmd.122.000958.
[7]	SUN Q, LI S, LIN R, et al. hUC-MSCs therapy for Crohn's disease:efficacy in TNBS-induced colitis in rats and pilot clinical study[J]. EBioMedicine, 2024, 103:105128. doi:10.1016/j.ebiom.2024.105128.
[8]	LYU S, LIU S, GUO X, et al. hP-MSCs attenuate severe acute pancreatitis in mice via inhibiting NLRP3 inflammasome-mediated acinar cell pyroptosis[J]. Apoptosis, 2024, 29(5/6):920-933. doi:10.1007/s10495-024-01946-5.
[9]	LI H, DU R, XIANG A, et al. Bone marrow mesenchymal stem cell-derived exosomal miR-181a-5p promotes M2 macrophage polarization to alleviate acute pancreatitis through ZEB2-mediated RACK1 ubiquitination[J]. FASEB J, 2024, 38(23):e70042. doi:10.1096/fj.202400803RR.
[10]	BRAID L R, WOOD C A, WIESE D M, et al. Intramuscular administration potentiates extended dwell time of mesenchymal stromal cells compared to other routes[J]. Cytotherapy, 2018, 20(2):232-244. doi:10.1016/j.jcyt.2017.09.013.
[11]	HERNANDA P Y, PEDROZA-GONZALEZ A, SPRENGERS D, et al. Multipotent mesenchymal stromal cells in liver cancer:implications for tumor biology and therapy[J]. Biochim Biophys Acta, 2014, 1846(2):439-445. doi:10.1016/j.bbcan.2014.08.008.
[12]	DOMINICI M, LE BLANC K, MUELLER I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International society for cellular therapy position statement[J]. Cytotherapy, 2006, 8(4):315-317. doi:10.1080/14653240600855905.
[13]	YUAN M, HU X, YAO L, et al. Mesenchymal stem cell homing to improve therapeutic efficacy in liver disease[J]. Stem Cell Res Ther, 2022, 13(1):179. doi:10.1186/s13287-022-02858-4.
[14]	JIANG W, XU J. Immune modulation by mesenchymal stem cells[J]. Cell Prolif, 2020, 53(1):e12712. doi:10.1111/cpr.12712.
[15]	ZOU Y, LIAO L, DAI J, et al. Mesenchymal stem cell-derived extracellular vesicles/exosome:a promising therapeutic strategy for intracerebral hemorrhage[J]. Regen Ther, 2023, 22:181-190. doi:10.1016/j.reth.2023.01.006.
[16]	WANG H, ALARCÓN C N, LIU B, et al. Genetically engineered and enucleated human mesenchymal stromal cells for the targeted delivery of therapeutics to diseased tissue[J]. Nat Biomed Eng, 2022, 6(7):882-897. doi:10.1038/s41551-021-00815-9.
[17]	SUN X, GAO Y, CHEN H, et al. From hair to pancreas:transplanted hair follicle mesenchymal stem cells express pancreatic progenitor cell markers in a rat model of acute pancreatitis[J]. Am J Transl Res, 2021, 13(3):1389-1399.
[18]	HUANG Q, CHENG X, LUO C, et al. Placental chorionic plate-derived mesenchymal stem cells ameliorate severe acute pancreatitis by regulating macrophage polarization via secreting TSG-6[J]. Stem Cell Res Ther, 2021, 12(1):337. doi:10.1186/s13287-021-02411-9.
[19]	LI H Y, HE H C, SONG J F, et al. Bone marrow-derived mesenchymal stem cells repair severe acute pancreatitis by secreting miR-181a-5p to target PTEN/Akt/TGF-β1 signaling[J]. Cell Signal, 2020, 66:109436. doi:10.1016/j.cellsig.2019.109436.
[20]	MA Z, XIE W, LUO T, et al. Exosomes from TNF-α preconditioned human umbilical cord mesenchymal stromal cells inhibit the autophagy of acinar cells of severe acute pancreatitis via shuttling bioactive metabolites[J]. Cell Mol Life Sci, 2023, 80(9):257. doi:10.1007/s00018-023-04861-1.
[21]	张亚东, 胡音音, 史光军. 脂肪间充质干细胞对重症急性胰腺炎大鼠炎性损伤的调节作用[J]. 中国现代普通外科进展, 2020, 23(8):594-599.
	ZHANG Y D, HU Y Y, SHI G J. Regulatory effect of adipose-derived mesenchymal stem cells on inflammatory injury in rats with severe acute pancreatitis[J]. Chinese Journal of Current Advances in General Surgery, 2020, 23(8):594-599. doi:10.3969/j.issn.1009-9905.2020.08.002.
[22]	LI S, LI H, ZHANGDI H, et al. Hair follicle-MSC-derived small extracellular vesicles as a novel remedy for acute pancreatitis[J]. J Control Release, 2022, 352:1104-1115. doi:10.1016/j.jconrel.2022.11.029.
[23]	黄少雄, 常诚, 李文生, 等. 间充质干细胞治疗重症急性胰腺炎临床疗效的观察[J]. 中华临床医师杂志, 2012, 6(11):3093-3096.
	HUANG S X, CHANG C, LI W S, et al. Clinical efficacy of mesenchymal stem cell therapy for severe acute pancreatitis[J]. Chinese Journal of Clinical Physicians, 2012, 6(11):3093-3096. doi:10.3877/cma.j.issn.1674-0785.2012.11.061.
[24]	SHIN I S, PARK C H, MOON J H, et al. Human bone marrow-derived clonal mesenchymal stem cells decrease the initial C`-reactive protein level in patients with moderately severe to severe acute pancreatitis[J]. Gastroenterology, 2023, 164(7):1317-1320.e2. doi:10.1053/j.gastro.2023.02.009.
[25]	GONG J, XIONG Z, YU W, et al. Bone marrow mesenchymal stem cells alleviate acute severe pancreatitis and promote lung repair via inhibiting NLRP3 inflammasome in rat[J]. Dig Dis Sci, 2024, 69(1):135-147. doi:10.1007/s10620-023-08189-5.
[26]	WANG J, TIAN J, WANG L, et al. Mesenchymal stem cells regulate M1 polarization of peritoneal macrophages through the CARD9-NF-κB signaling pathway in severe acute pancreatitis[J]. J Hepatobiliary Pancreat Sci, 2023, 30(3):338-350. doi:10.1002/jhbp.1205.
[27]	ZHAO D, YU W, XIE W, et al. Bone marrow-derived mesenchymal stem cells ameliorate severe acute pancreatitis by inhibiting oxidative stress in rats[J]. Mol Cell Biochem, 2022, 477(12):2761-2771. doi:10.1007/s11010-022-04476-3.
[28]	YANG H, LIU Y, YAO J, et al. Mesenchymal stem cells inhibit ferroptosis by activating the Nrf2 antioxidation pathway in severe acute pancreatitis-associated acute lung injury[J]. Eur J Pharmacol, 2024, 967:176380. doi:10.1016/j.ejphar.2024.176380.
[29]	JUNG K H, YI T, SON M K, et al. Therapeutic effect of human clonal bone marrow-derived mesenchymal stem cells in severe acute pancreatitis[J]. Arch Pharm Res, 2015, 38(5):742-751. doi:10.1007/s12272-014-0465-7.
[30]	HE Z, HUA J, QIAN D, et al. Intravenous hMSCs ameliorate acute pancreatitis in mice via secretion of tumor necrosis factor-α stimulated gene/protein 6[J]. Sci Rep, 2016,6:38438. doi:10.1038/srep38438.
[31]	MA Z, SONG G, ZHAO D, et al. Bone marrow-derived mesenchymal stromal cells ameliorate severe acute pancreatitis in rats via hemeoxygenase-1-mediated anti-oxidant and anti-inflammatory effects[J]. Cytotherapy, 2019, 21(2):162-174. doi:10.1016/j.jcyt.2018.11.013.
[32]	ABDELHAFEZ D, ABOELKOMSAN E, EL SADIK A, et al. The role of mesenchymal stem cells with ascorbic acid and N-acetylcysteine on TNF-α,IL 1β,and NF-κβ expressions in acute pancreatitis in albino rats[J]. J Diabetes Res, 2021,2021:6229460. doi:10.1155/2021/6229460.
[33]	景光旭, 王张鹏, 刘忠钰, 等. 低氧预处理胎盘间充质干细胞减轻重症急性胰腺炎模型小鼠胰腺组织损伤[J]. 基础医学与临床, 2023, 43(9):1346-1352.
	JING G X, WANG Z P, LIU Z Y, et al. Hypoxic preconditioning placental mesenchymal stem cells alleviate pathological lesion in mouse models with severe acute pancreatitis[J]. Basic and Clinical Medicine, 2023, 43(9):1346-1352. doi:10.16352/j.issn.1001-6325.2023.09.1346.
[34]	REN S, PAN L, YANG L, et al. miR-29a-3p transferred by mesenchymal stem cells-derived extracellular vesicles protects against myocardial injury after severe acute pancreatitis[J]. Life Sci, 2021, 272:119189. doi:10.1016/j.lfs.2021.119189.
[35]	LIU D, SONG G, MA Z, et al. Resveratrol improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells in rats with severe acute pancreatitis[J]. Int Immunopharmacol, 2020, 80:106128. doi:10.1016/j.intimp.2019.106128.
[36]	XIE W, LUO T, MA Z, et al. Tumor necrosis factor alpha preconditioned umbilical cord mesenchymal stem cell-derived extracellular vesicles enhance the inhibition of necroptosis of acinar cells in severe acute pancreatitis[J]. Tissue Eng Part A, 2023, 29(23/24):607-619. doi:10.1089/ten.TEA.2023.0139.
[37]	SONG G, LIU D, GENG X, et al. Bone marrow-derived mesenchymal stem cells alleviate severe acute pancreatitis-induced multiple-organ injury in rats via suppression of autophagy[J]. Exp Cell Res, 2019, 385(2):111674. doi:10.1016/j.yexcr.2019.111674.
[38]	SONG G, ZHOU J, SONG R, et al. Long noncoding RNA H19 regulates the therapeutic efficacy of mesenchymal stem cells in rats with severe acute pancreatitis by sponging miR-138-5p and miR-141-3p[J]. Stem Cell Res Ther, 2020, 11(1):420. doi:10.1186/s13287-020-01940-z.
[39]	REN R, REN W, ZHANG Y, et al. Breaking the chain in organ failure:role of umbilical cord and bone marrow derived mesenchymal stem cells in treatment of severe acute pancreatitis[J]. Heliyon, 2024, 10(16):e35785. doi:10.1016/j.heliyon.2024.e35785.
[40]	苟英, 吴东叶, 黄启林, 等. 胎盘MSCs移植改善重症急性胰腺炎大鼠肠屏障功能研究[J]. 长春中医药大学学报, 2021, 37(5):1003-1008.
	GOU Y, WU D Y, HUANG Q L, et al. Effect of the placental MSCs transplantation on the intestinal barrier function in rats with severe acute pancreatitis[J]. Journal of Changchun University of Chinese Medicine, 2021, 37(5):1003-1008. doi:10.13463/j.cnki.cczyy.2021.05.016.
[41]	马博, 周军, 李建刚, 等. 腹腔内注射骨髓间充质干细胞对急性胰腺炎小鼠相关肺损伤的影响及相关机制研究[J]. 临床和实验医学杂志, 2021, 20(7):673-676.
	MA B, ZHOU J, LI J G, et al. Effects of intraperitoneal injection of bone marrow mesenchymal stem cells on lung injury associated with acute pancreatitis in mice and its mechanism[J]. Journal of Clinical and Experimental Medicine, 2021, 20(7):673-676. doi:10.3969/j.issn.1671-4695.2021.07.001.
[42]	周国华. 骨髓间充质干细胞通过抑制mtDNA-STING-NF-κB信号通路治疗大鼠急性胰腺炎肺损伤[D]. 大连医科大学, 2022.
	ZHOU G H. Bone marrow mesenchymal stem cells reduce acute pancreatitis-associated lung injury by inhibiting mtDNA-STING-NF-κB signaling pathway[D]. Dalian Medical University, 2022. doi:10.26994/d.cnki.gdlyu.2022.001114.
[43]	刘晓君. 清胰汤联合骨髓间充质干细胞对重症急性胰腺炎时肺气血屏障损伤的保护作用[D]. 大连医科大学, 2023.
	LIU X J. Qingyi deccotion combined with bone marrow mesenchymal stem cells protects lung air-blood barrier damage in severe acute pancreatitis[D]. Dalian Medical University, 2023. doi:10.26994/d.cnki.gdlyu.2023.000189.
[44]	姚义, 张明基. 骨髓间充质干细胞对重症急性胰腺炎大鼠相关肺损伤的实验研究[J]. 福建医药杂志, 2024, 46(1):120-124,181. YAO Y,
	ZHANG M J, Experimental study of bone marrow mesenchymal stem cells on lung injury associated with severe acute pancreatitis in rats[J]. Fujian Medical Journal, 2024, 46(1):120-124,181. doi:10.20148/j.fmj.2024.01.033.
[45]	CHEN M, CHEN J, HUANG W, et al. Exosomes from human induced pluripotent stem cells derived mesenchymal stem cells improved myocardial injury caused by severe acute pancreatitis through activating Akt/Nrf2/HO-1 axis[J]. Cell Cycle, 2022, 21(15):1578-1589. doi:10.1080/15384101.2022.2057762.
[46]	LIU H, LIU S, SONG X, et al. Nanoparticle encapsulated CQ/TAM combination harmonizes with MSCs in arresting progression of severity in AP mice through iNOS (IDO) signaling[J]. Mater Today Bio, 2022, 14:100226. doi:10.1016/j.mtbio.2022.100226.
[47]	KOJIMA H, KUSHIGE H, YAGI H, et al. Combinational treatment involving decellularized extracellular matrix hydrogels with mesenchymal stem cells increased the efficacy of cell therapy in pancreatitis[J]. Cell Transplant, 2023,32:9636897231170437. doi:10.1177/09636897231170437.

间充质干细胞治疗急性胰腺炎的机制及研究进展

Mechanism and research progress of mesenchymal stem cell therapy for acute pancreatitis

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