From the AGA Journals

Mesenteric adipose–derived stromal cell lactoferrin may mediate protective effects in Crohn’s disease

Publish date: May 31, 2018

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Fat is not always bad

Inflammatory bowel disease (IBD), including Crohn’s disease, is a chronic inflammatory condition of the gastrointestinal tract that is often associated with changes in adipose tissue. However, the pathophysiological significance of fat wrapping in Crohn’s disease remains largely elusive. A correlation of IBD with obesity has been established by a number of studies, which report 15%-40% of adults with IBD are obese. Obesity is found to have a negative effect on disease activity and progression to surgery in patients with Crohn’s disease. In contrast, adipose-derived stromal or stem cells exhibit regenerative and anti-inflammatory function.

A recent study published in Cellular and Molecular Gastroenterology and Hepatology by Jill M. Hoffman and her colleagues highlighted the immune-modulatory function of adipose-derived stromal cells (ADSCs) in Crohn’s disease patients. They observed that patient-derived ADSCs promote colonocyte proliferation and exhibit distinct gene expression patterns, compared with healthy controls. The authors successfully identified ADSC-derived lactoferrin, an iron binding glycoprotein and an antimicrobial peptide, as a potential immunoregulatory molecule.

Dr. Amlan Biswas

They concluded that the disease-dependent alterations in mesenteric adipose tissue–derived ADSCs might have a protective role in the pathophysiology of Crohn’s disease. The study elegantly highlighted the therapeutic potential of lactoferrin in IBD and provided new insight into the biology of ADSC.

Amlan Biswas, PhD, is an instructor in pediatrics at Harvard Medical School, Boston, and is affiliated with Boston Children’s Hospital in the division of gastroenterology and nutrition. He has no conflicts of interest


 

FROM CMGH


Levels of lactoferrin mRNA (validated by real time polymerase chain reaction; 92.70 ± 18.41 versus 28.98 ± 5.681; P less than .05) and protein (validated by ELISA; 142.2 ± 5.653 versus 120.1 ± 3.664; P less than .01) were increased in human mesenteric ADSCs and conditioned media from CD patients, respectively, compared with that from controls.

“Compared with mice receiving vehicle injections, mice receiving daily injections of lactoferrin had improved clinical scores (5.625 ± 0.565 versus 11.125 ± 0.743; n = 8) and colon length at day 7 (6.575 ± 0.1688 versus 5.613 ± 0.1445; n = 8). In addition, we found epithelial cell proliferation was increased in the colons of lactoferrin-treated mice with colitis, compared with vehicle-treated controls (3.548e7 ± 1.547e6 versus 1.184e7 ± 2.915e6; P less than .01),” said the authors.

Collectively, the presented data was suggestive of a protective role of mesenteric adipose tissue–derived mediators, such as lactoferrin, in the pathophysiology of CD.

The study was supported by the Broad Medical Research Program (IBD-0390), an NIDDK Q51856 Ruth L. Kirschstein National Research Service Award Postdoctoral Fellowship 1857 (F32 DK102322), the Neuroendocrine Assay and Models of Gastrointestinal Function and Disease Cores (P50 DK 64539), an AGA-1858 Broad Student Research Fellowship, the Blinder Center for Crohn’s 1859 Disease Research, the Eli and Edythe Broad Chair, and NIH/NIDDK grant DK047343.

The authors disclosed no conflicts of interest.

SOURCE: Hoffman J et al. Cell Molec Gastro Hepatol. doi: 10.1016/j.jcmgh.2018.02.001.

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