Protective effect of placenta-derived mesenchymal stem cell transplantation against severe acute pancreatitis in rats

Qilin HUANG; Yi YANG; Chen LUO; Shuai LI; Lijun TANG; Hongyu SUN

doi:10.16016/j.1000-5404.201910113

您当前的位置：

首页 >

文章列表页 >

Protective effect of placenta-derived mesenchymal stem cell transplantation against severe acute pancreatitis in rats

Basic Medicine | 更新时间：2026-01-09

- Protective effect of placenta-derived mesenchymal stem cell transplantation against severe acute pancreatitis in rats
- Journal of Third Military Medical University Vol. 42, Issue 7, Pages: 646-655(2020)
- 作者机构：
  
  1.610031 成都，西南交通大学医学院
  2.610083 成都，西部战区总医院胰腺损伤与修复四川省重点实验室
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81772001);the National Clinical Key-discipline Construction Program of China(41792113)
- DOI：10.16016/j.1000-5404.201910113
  CLC： R329.1;R576;R617
- Received：18 October 2019，
  
  Revised：2019-12-13，
  
  Published：15 April 2020
- 稿件说明：
移动端阅览
Qilin HUANG, Yi YANG, Chen LUO, et al. Protective effect of placenta-derived mesenchymal stem cell transplantation against severe acute pancreatitis in rats[J]. Journal of Third Military Medical University, 2020, 42(7): 646-655.
DOI：

Qilin HUANG, Yi YANG, Chen LUO, et al. Protective effect of placenta-derived mesenchymal stem cell transplantation against severe acute pancreatitis in rats[J]. Journal of Third Military Medical University, 2020, 42(7): 646-655. DOI： 10.16016/j.1000-5404.201910113.

摘要

目的

研究胎盘间充质干细胞(placenta-derived mesenchymal stem cells

P-MSCs)对大鼠重症急性胰腺炎(severe acute pancreatitis

SAP)的保护作用。

方法

健康成年雄性SD大鼠32只，随机分为对照组、P-MSCs组、SAP组和SAP+P-MSCs组，每组8只。采用4%牛磺胆酸钠胆胰管逆行注射法建立SAP大鼠模型，造模结束后12 h与3

6 h经尾静脉注射P-MSCs(1×10

个/100 g)。大鼠在P-MSCs第一次输注后72 h处死，HE染色评估胰腺损伤程度，ELISA法测定血清中炎症因子、淀粉酶与脂肪酶浓度，qRT-PCR检测胰腺组织中炎症因子基因表达水平，免疫组化法检测胰腺组织中巨噬细胞浸润情况。

结果

体外输注的P-MSCs有向损伤部位定植的特性。与SAP组相比，SAP+P-MSCs组胰腺病理评分明显降低(

0.05)；血清中淀粉酶、脂肪酶、IL-1β、IL-6与TNF-α浓度明显降低(

0.05)，而IL-10、IL-4和TGF-β浓度明显升高(

0.05)；胰腺组织中IL-1β与TNF-α mRNA表达水平明显降低(

0.05)，IL-10与IL-4 mRNA表达水平明显升高(

0.05)。此外，P-MSCs可以有效减轻胰腺组织中巨噬细胞浸润。

结论

P-MSCs能有效减轻SAP大鼠胰腺局部炎症反应与全身炎症反应，其减轻胰腺局部炎症反应可能与其减少胰腺局部巨噬细胞与中性粒细胞浸润有关。

Abstract

Objective

To investigate the protective effects of human placenta-derived mesenchymal stem cell (P-MSC) transplantation against severe acute pancreatitis (SAP) in rats.

Methods

A total of 32 healthy adult male Sprague-Dawley (SD) rats were randomly divided into control group

P-MSC group

SAP and SAP+P-MSCs group (

=8)

and in the latter 2 groups

SAP was induced by retrograde injection of 4% sodium taurocholate into the common biliopancreatic duct. P-MSCs (1×10

cells/100 g) were delivered through the tail vein of the rats at 12 and 36 h after the induction of SAP. All the rats were sacrificed 72 h after the first P-MSC infusion. HE staining was used to assess the pancreatic pathologies of the rats after the treatments. The serum levels of the pro- and anti-inflammatory mediators

amylase and lipase were determined by ELISA

and the mRNA expression levels of the inflammatory mediators in the pancreatic tissue were detected using qRT-PCR. Immunohistochemistry was performed to examine macrophage infiltration in the pancreatic tissue of the rats.

Results

Homing of the infused P-MSCs to the injury site was observed in the rats with SAP. Transplantation of P-MSCs significantly ameliorated histopatholo

gical injury and lowered pancreatic pathological score of the pancreas

reduced serum levels of amylase

lipase

interleukin-1β (IL-1β)

IL-6 and tumor necrosis factor-α (TNF-α) (

0.05)

increased serum levels of IL-10

IL-4 and transforming growth factor-β (TGF-β) (

0.05)

decreased the expression levels of IL-1β and TNF-α (

0.05) and increased the expression of IL-10 and IL-4 in the pancreatic tissue (

0.05) of the rats with SAP. In addition

P-MSC transplantation effectively reduced macrophage infiltration in the pancreatic tissue of the rats.

Conclusion

Transplantation of P-MSCs can effectively alleviate local inflammatory response in the pancreas and systemic inflammatory response in rats with SAP probably by reducing local macrophage and neutrophil infiltration in the pancreas.

关键词

Keywords

references

FORSMARK C E, SWAROOP VEGE S, WILCOX C M. Acute pancreatitis[J]. N Engl J Med, 2016, 375(20): 1972-1981. DOI: 10.1056/nejmra1505202.

GUKOVSKAYA A S, GUKOVSKY I, ALGVL H, et al . Autophagy, inflammation, and immune dysfunction in the pathogenesis of pancreatitis[J ] . Gastroenterology, 2017, 153(5): 1212-1226. DOI: 10.1053/j.gastro.2017.08.071.

MANOHAR M, VERMA A K, VENKATESHAIAH S U, et al . Pathogenic mechanisms of pancreatitis[J ] . World J Gastrointest Pharmacol Ther, 2017, 8(1): 10. DOI: 10.4292/wjgpt.v8.i1.10.

SHRIVASTAVA P, BHATIA M. Essential role of monocytes and macrophages in the progression of acute pancreatitis[J]. World J Gastroenterol, 2010, 16(32): 3995-4002. DOI: 10.3748/wjg.v16.i32.3995.

GEA-SORLÍ S, CLOSA D. Role of macrophages in the progression of acute pancreatitis[J]. World J Gastrointest Pharmacol Ther, 2010, 1(5): 107-111. DOI: 10.4292/wjgpt.v1.i5.107.

JUNG K H, SONG S N, YI T, et al . Human bone marrow-derived clonal mesenchymal stem cells i nhibit inflammation and reduce acute pancreatitis in rats[J ] . Gastroenterology, 2011, 140(3): 998-1008. DOI: 10.1053/j.gastro.2010.11.047.

WALTER J, WARE L B, MATTHAY M A. Mesenchymal stem cells: mechanisms of potential therapeutic benefit in ARDS and sepsis[J]. Lancet Respir Med, 2014, 2(12): 1016-1026. DOI: 10.1016/S2213-2600(14)70217-6.

MA Z L, SONG G D, ZHAO D B, et al . Bone marrow-derived mesenchymal stromal cells ameliorate severe acute pancreatitis in rats via hemeoxygenase-1-mediated anti-oxidant and anti-inflammatoryeffects[J ] . Cytotherapy, 2019, 21(2): 162-174. DOI: 10.1016/j.jcyt.2018.11.013..

QIAN D H, SONG G D, MA Z L, et al . MicroRNA-9 modified bone marrow-derived mesenchymal stem cells (BMSCs) repair severe acute pancreatitis (SAP) via inducing angiogenesis in rats[J ] . Stem Cell Res Ther, 2018, 9(1): 282. DOI: 10.1186/s13287-018-1022-y.

YANG J, SU J, XI S S, et al . Human umbilical cord mesenchymal stem cells pretreated with angiotensin-Ⅱ attenuate pancreas injury of rats with severe acute pancreatitis[J ] . Biomedecine Pharmacother, 2019, 117: 109052. DOI: 10.1016/j.biopha.2019.109052.

HUANG Q, YANG Y, LUO C, et al . An efficient protocol to generate placental chorionic plate-derived mesenchymal stem cells with superior proliferative and immunomodulatory properties[J ] . Stem Cell Res Ther, 2019, 10(1): 301. DOI: 10.1186/s13287-019-1405-8.

SCHMIDT J, RATTNER D W, LEWANDROWSKI K, et al . A better model of acute pancreatitis for evaluating therapy[J ] . Ann Surg, 1992, 215(1): 44-56. DOI: 10.1097/00000658-199201000-00007.

SHI Y F, WANG Y, LI Q, et al . Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases[J ] . Nat Rev Nephrol, 2018, 14(8): 493-507. DOI: 10.1038/s41581-018-0023-5.

SHI Y H, SHI H, NOMI A, et al . Mesenchymal stem cell-derived extracellular vesicles: a new impetus of promoting angiogenesis in tissue regeneration[J ] . Cytotherapy, 2019, 21(5): 497-508. DOI: 10.1016/j.jcyt.2018.11.012.

LIANG L, LI Z J, MA T, et al . Transplantation of human placenta-derived mesenchymal stem cells alleviates critical limb ischemia in diabetic nude rats[J ] . Cell Transplant, 2017, 26(1): 45-61. DOI: 10.3727/096368916X69 2726.

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.

AHMED S M, MORSI M, GHONEIM N I, et al . Mesenchymal stromal cell therapy for pancreatitis: A systematic review[J ] . Oxid Med Cell Longev, 2018, 2018: 3250864. DOI: 10.1155/2018/3250864.

XU LL, LIU Y M, SUN Y X, et al . Tissue source determines the differentiation potentials of mesenchymal stem cells: a comparative study of human mesenchymal stem cells from bone marrow and adipose tissue[J ] . Stem Cell Res Ther, 2017, 8(1): 275. DOI: 10.1186/s13287-017-0716-x.

LI X Y, BAI J P, JI X F, et al . Comprehensive characterization of four different populations of human mesenchymal stem cells as regards their immune properties, proliferation and differentiation[J ] . Int J Mol Med, 2014, 34(3): 695-704. DOI: 10.3892/ijmm.2014.1821.

TALWADEKAR M D, KALE V P, LIMAYE L S. Placenta-derived mesenchymal stem cells possess better immunoregulatory properties compared to their cord-derived counterparts-a paired sample study[J]. Sci Rep, 2015, 5: 15784. DOI: 10.1038/srep15784.

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.

ZHAO W A, PHINNEY D G, BONNET D, et al . Mesenchymal stem cell biodistribution, migration, and homing in vivo [J ] . Stem Cells Int, 2014, 2014: 292109. DOI: 10.1155/2014/292109..

HE Z G, HUA J, QIAN D H, 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.

QU B, CHU Y J, ZHU F, et al . Granulocyte colony-stimulating factor enhances the therapeutic efficacy of bone marrow mesenchymal stem cell transplantation in rats with experimental acute pancreatitis[J ] . Oncotarget, 2017, 8(13): 21305-21314. DOI: 10.18632/oncotarget.15515.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Hypoxia drives spermatogenic impairment by triggering lysosome-dependent death of Leydig cells via M1 macrophage polarization

Protein phosphatase 2A promotes mitophagy to alleviate fructose-induced mitochondrial oxidative damage in M2-type macrophages

INKA2-AS1 promotes migration, invasion and macrophage-related immunosuppression in hepatocellular carcinoma

Ferrostatin-1 attenuates inflammatory response to hypoxic lung injury at plateau by inhibiting ferroptosis in lung epithelial cells

Effect of miR-382 overexpressing tumor-associated macrophages on biological properties of triple-negative breast cancer 4T1 cells

Related Author

MENG Dan

HE Wei

ZENG Jitao

LI Xiaoman

LAN Li

LONG Yijin

LI Huilian

WANG Minghong

Related Institution

Reproductive Medical Center， First Affiliated Hospital, College of Basic Medical Science，Army Medical University （Third Military Medical University）

Institute of Immunology, College of Basic Medical Science，Army Medical University （Third Military Medical University）

Department of Immunology， School of Basic Medical Sciences, School of Public Health， Guangxi Medical University

Key Laboratory of Basic Medical Sciences of Guangxi Higher Education Institutions, School of Public Health， Guangxi Medical University

Department of Nutrition and Food Hygiene, School of Public Health， Guangxi Medical University

⁰