Mesenteric Adipose-derived Stromal Cells From Crohn's Disease Patients Induce Protective Effects in Colonic Epithelial Cells and Mice With Colitis

被引：15

作者：

Hoffman, Jill M. ^{[1
]}

Sideri, Aristea ^{[1
]}

Ruiz, Jonathan J. ^{[1
]}

Stavrakis, Dimitris ^{[1
]}

Shih, David Q. ^{[2
]}

Turner, Jerrold R. ^{[3
,4
]}

Pothoulakis, Charalabos ^{[1
]}

Karagiannides, Iordanes ^{[1
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Ctr Inflammatory Bowel Dis, 675 Charles E Young Dr South,MRL Bldg 1220, Los Angeles, CA 90095 USA

[2] Cedars Sinai Med Ctr, Inflammatory Bowel & Immunobiol Res Inst, Los Angeles, CA 90048 USA

[3] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA

[4] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA USA

来源：

CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY | 2018年 / 6卷 / 01期

关键词：

Mesenteric Adipose Tissue; Inflammatory Bowel Disease; Preadipocytes; Intestinal Epithelium; IRRITABLE-BOWEL-SYNDROME; BOVINE LACTOFERRIN SUPPLEMENTATION; MUCOSAL BIOPSY SUPERNATANTS; ENDOCRINE ORGAN; CLINICAL-COURSE; ENDOTHELIAL-CELLS; MOLECULAR-CLONING; FECAL LACTOFERRIN; MURINE COLITIS; STEM-CELLS;

D O I：

10.1016/j.jcmgh.2018.02.001

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Mesenteric adipose tissue hyperplasia is a hallmark of Crohn's disease (CD). Recently, we showed that mesenteric adipose-derived stromal cells (ADSCs) from CD, ulcerative colitis, and control patients synthesize and release adipokines in a disease-dependent manner. Here we examined the expression profiles of CD and control patient-derived mesenteric ADSCs and studied the effects of their extracellular mediators on colonocyte signaling in vitro and experimental colitis in vivo. ADSCs were isolated from mesenteric fat of control and CD patients. Microarray profiling and network analysis were performed in ADSCs and human colonocytes treated with conditioned media from cultured ADSCs. Mice with acute colitis received daily injections of conditioned media from patient-derived ADSCs, vehicle, or apolactoferrin. Proliferative responses were evaluated in conditioned media-treated colonocytes and mouse colonic epithelium. Total protein was isolated from cultured colonocytes after treatment with apolactoferrin for Western blot analysis of phosphorylated intracellular signaling kinases. Microarray profiling revealed differential mRNA expression in CD patient-derived ADSCs compared with controls, including lactoferrin. Administration of CD patient-derived medium or apolactoferrin increased colonocyte proliferation compared with controls. Conditioned media from CD patient-derived ADSCs or apolactoferrin attenuated colitis severity in mice and enhanced colonocyte proliferation in vivo. ADSCs from control and CD patients show disease-dependent inflammatory responses and alter colonic epithelial cell signaling in vitro and in vivo. Furthermore, we demonstrate lactoferrin production by adipose tissue, specifically mesenteric ADSCs. We suggest that mesenteric ADSC-derived lactoferrin may mediate protective effects and participate in the pathophysiology of CD by promoting colonocyte proliferation and the resolution of inflammation.

引用

页码：1 / 16

页数：16

共 62 条

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