Isolation of Quiescent Human Pancreatic Stellate Cells: A Promising in vitro Tool for Studies of Human Pancreatic Stellate Cell Biology

被引：49

作者：

Vonlaufen, Alain ^{[2
,3
]}

Phillips, Phoebe A. ^{[2
]}

Yang, Lu ^{[2
]}

Xu, Zhihong ^{[2
]}

Fiala-Beer, Eva ^{[2
]}

Zhang, Xuguo ^{[2
]}

Pirola, Romano C.

Wilson, Jeremy S. ^{[2
]}

Apte, Minoti V. ^{[1
,2
]}

机构：

[1] Univ New S Wales, S Western Sydney Clin Sch, Fac Med, Pancreat Res Grp, Sydney, NSW 2052, Australia

[2] Univ New S Wales, Sch Med Sci, Sydney, NSW 2052, Australia

[3] Univ Hosp, Dept Gastroenterol, Geneva, Switzerland

来源：

PANCREATOLOGY | 2010年 / 10卷 / 04期

关键词：

Human pancreatic stellate cells; quiescent; Activation; pancreatic stellate cells; Extracellular matrix production; Proliferation; Migration; INDUCE FIBROSIS; CANCER; IDENTIFICATION; FIBROGENESIS; MIGRATION; CYTOKINES; CULTURE;

D O I：

10.1159/000260900

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background: Pancreatic stellate cells (PSCs) play a critical role in pancreatic fibrosis. To date, human PSC biology has been studied using cancer-or inflammation-associated (pre-activated) PSCs, but an in vitro model of quiescent normal human PSCs (NhPSCs) has been lacking. Aims: To (i) isolate and characterize quiescent NhPSCs, and (ii) evaluate the response of culture-activated NhPSCs to cytokines and LPS. Methods: Quiescent NhPSCs were isolated from normal pancreatic tissue using density gradient centrifugation. PSC markers, glial fibrillary acidic protein (GFAP), desmin, alpha-smooth muscle actin (alpha SMA) and the lipopolysaccharide (LPS) receptors TLR4 and CD14 were identified by immuno-blotting and immunocytochemistry. The effect of platelet-derived growth factor (PDGF), transforming growth factor beta (TGF beta) and LPS on NhPSC activation was also assessed. Results: Freshly isolated NhPSCs displayed a polygonal appearance with refringent cytoplasmic lipid droplets. Culture-activated NhPSCs expressed GFAP, desmin, alpha SMA, TLR4 and CD14, and were responsive to PDGF, TGF beta and LPS. Conclusion: Isolated NhPSCs expressed the same markers as rat PSCs and human cancer-associated PSCs and responded to PDGF and TGF beta similarly to rat PSCs. NhPSC preparations provide a useful in vitro tool to study the biology of PSCs in their physiological, non-activated state. Copyright (C) 2010 S. Karger AG, Basel and IAP

引用

页码：434 / 443

页数：10

共 18 条

[1] Pancreatic stellate cells are activated by proinflammatory cytokines: implications for pancreatic fibrogenesis [J].

Apte, MV ;

Haber, PS ;

Darby, SJ ;

Rodgers, SC ;

McCaughan, GW ;

Korsten, MA ;

Pirola, RC ;

Wilson, JS .

GUT, 1999, 44 (04) :534-541

[2] Mechanisms of pancreatic fibrosis [J].

Apte, MV ;

Wilson, JS .

DIGESTIVE DISEASES, 2004, 22 (03) :273-279

[3] Desmoplastic reaction in pancreatic cancer - Role of pancreatic stellate cells [J].

Apte, MV ;

Park, S ;

Phillips, PA ;

Santucci, N ;

Goldstein, D ;

Kumar, RK ;

Ramm, GA ;

Buchler, M ;

Friess, H ;

McCarroll, JA ;

Keogh, G ;

Merrett, N ;

Pirola, R ;

Wilson, JS .

PANCREAS, 2004, 29 (03) :179-187

[4] Does alcohol directly stimulate pancreatic fibrogenesis? Studies with rat pancreatic stellate cells [J].

Apte, MV ;

Phillips, PA ;

Fahmy, RG ;

Darby, SJ ;

Rodgers, SC ;

McCaughan, GW ;

Korsten, MA ;

Pirola, RC ;

Naidoo, D ;

Wilson, JS .

GASTROENTEROLOGY, 2000, 118 (04) :780-794

[5] Periacinar stellate shaped cells in rat pancreas: identification, isolation, and culture [J].

Apte, MV ;

Haber, PS ;

Applegate, TL ;

Norton, ID ;

McCaughan, GW ;

Korsten, MA ;

Pirola, RC ;

Wilson, JS .

GUT, 1998, 43 (01) :128-133

[6] Pancreatic carcinoma cells induce fibrosis by stimulating proliferation and matrix synthesis of stellate cells [J].

Bachem, MG ;

Schünemann, M ;

Ramadani, M ;

Siech, M ;

Beger, H ;

Buck, A ;

Zhou, SX ;

Schmid-Kotsas, A ;

Adler, G .

GASTROENTEROLOGY, 2005, 128 (04) :907-921

[7] Identification, culture, and characterization of pancreatic stellate cells in rats and humans [J].

Bachem, MG ;

Schneider, E ;

Gross, H ;

Weidenbach, H ;

Schmid, RM ;

Menke, A ;

Siech, M ;

Beger, H ;

Grünert, A ;

Adler, G .

GASTROENTEROLOGY, 1998, 115 (02) :421-432

[8] Cancer-Stellate Cell Interactions Perpetuate the Hypoxia-Fibrosis Cycle in Pancreatic Ductal Adenocarcinoma [J].

Erkan, Mert M. ;

Reiser-Erkan, Carolin ;

Michalski, Christoph W. ;

Deucker, Stefanie ;

Sauliunaite, Danguole ;

Streit, Sylvia ;

Esposito, Irene ;

Friess, Helmut ;

Kleeff, Jorg .

NEOPLASIA, 2009, 11 (05) :497-508

[9] Hepatic stellate cells: Protean, multifunctional, and enigmatic cells of the liver [J].

Friedman, Scott L. .

PHYSIOLOGICAL REVIEWS, 2008, 88 (01) :125-172

[10] Cancer-associated stroma fibroblasts promote pancreatic tumor progression [J].

Hwang, Rosa F. ;

Moore, Todd ;

Arumugam, Thiruvengadain ;

Ramachandran, Vijaya ;

Amos, Keith D. ;

Rivera, Armando ;

Ji, Baoan ;

Evans, Douglas B. ;

Logsdon, Craig D. .

CANCER RESEARCH, 2008, 68 (03) :918-926

← 1 2 →