Ironing out the details of intestinal repair

The increasing use of mechanical sutures in urological surgery has highlighted some particular problems about the behaviour of the intestinal wall around the mechanical anastomosis. The Authors report on 160 bladder substitutions performed between April 1990 and April 1994. Histological and biological evaluation of intestinal repair and epithelisation show how the newly formed mucosa covers the steel stitches, isolating them from contact with the urine, so their potency to favour stone growth is very low. The particular shape and arrangement of stitches done with the GIA stapling device ensure a stronger and better vascularised suture than one done manually. In conclusion, the use of stapling devices in urological surgery offers the advantages of time saving and accuracy and safety of the sutures.

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A novel Toll-like receptor 4 antagonist antibody ameliorates inflammation but impairs mucosal healing in murine colitis

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.90496.2008 ◽

2009 ◽

Vol 296 (6) ◽

pp. G1167-G1179 ◽

Cited By ~ 107

Author(s):

Ryan Ungaro ◽

Masayuki Fukata ◽

David Hsu ◽

Yasmin Hernandez ◽

Keith Breglio ◽

...

Keyword(s):

Activity Index ◽

Disease Activity Index ◽

Mucosal Healing ◽

Transfer Model ◽

Innate Immune Responses ◽

Murine Colitis ◽

Dss Colitis ◽

Tnf Α ◽

Inflammatory Bowel ◽

Intestinal Repair

Dysregulated innate immune responses to commensal bacteria contribute to the development of inflammatory bowel disease (IBD). TLR4 is overexpressed in the intestinal mucosa of IBD patients and may contribute to uncontrolled inflammation. However, TLR4 is also an important mediator of intestinal repair. The aim of this study is to examine the effect of a TLR4 antagonist on inflammation and intestinal repair in two murine models of IBD. Colitis was induced in C57BL/6J mice with dextran sodium sulfate (DSS) or by transferring CD45Rbhi T cells into RAG1−/− mice. An antibody (Ab) against the TLR4/MD-2 complex or isotype control Ab was administered intraperitoneally during DSS treatment, recovery from DSS colitis, or induction of colitis in RAG1−/− mice. Colitis severity was assessed by disease activity index (DAI) and histology. The effect of the Ab on the inflammatory infiltrate was determined by cell isolation and immunohistochemistry. Mucosal expression of inflammatory mediators was analyzed by real-time PCR and ELISA. Blocking TLR4 at the beginning of DSS administration delayed the development of colitis with significantly lower DAI scores. Anti-TLR4 Ab treatment decreased macrophage and dendritic cell infiltrate and reduced mucosal expression of CCL2, CCL20, TNF-α, and IL-6. Anti-TLR4 Ab treatment during recovery from DSS colitis resulted in defective mucosal healing with lower expression of COX-2, PGE2, and amphiregulin. In contrast, TLR4 blockade had minimal efficacy in ameliorating inflammation in the adoptive transfer model of chronic colitis. Our findings suggest that anti-TLR4 therapy may decrease inflammation in IBD but may also interfere with colonic mucosal healing.

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Biological behaviour of the bowel mucose in bladder substitution using stapler devices: A two years experience

Urologia Journal ◽

10.1177/039156039205901s20 ◽

1992 ◽

Vol 59 (1_suppl) ◽

pp. 62-64

Author(s):

G. Muto ◽

M. Moroni ◽

M. Ollino ◽

R. Bozzo

Keyword(s):

Urinary Diversion ◽

Intestinal Wall ◽

Biological Behaviour ◽

Stapling Devices ◽

Urological Surgery ◽

Biological Studies ◽

Bladder Substitution ◽

Stapler Devices ◽

Mechanical Anastomosis ◽

Intestinal Repair

The largest use of mechanical sutures in urological surgery for their undoubt advantages has pointed out some particular problems about the behavior of the intestinal wall at the level of the mechanical anastomosis. The Authors report a study performed on 45 urinary diversion (including 12 orthotopic ileal bladders). Histological and biological studies on intestinal repair and epitelization show how the neoformed mucosa overlaps the steel stitches, putting them far from the urine. In this way their potency to favour the growth of urinary stoned is very low. At least, the particular shape and disposition of the stitches shooted by GIA stapling devices makes the suture stronger and better vascularized than those performed manually with adsorbable materials.

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Activation of mTORC1 by LSECtin in macrophages directs intestinal repair in inflammatory bowel disease

Cell Death and Disease ◽

10.1038/s41419-020-03114-4 ◽

2020 ◽

Vol 11 (10) ◽

Author(s):

Qian Li ◽

Hanxing cheng ◽

Yuanping Liu ◽

Xiaowen Wang ◽

Fuchu He ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Growth Factors ◽

Bowel Disease ◽

Apoptotic Cell ◽

Tissue Growth ◽

Apoptotic Cell Clearance ◽

Cell Clearance ◽

Inflammatory Bowel ◽

Intestinal Repair ◽

Inflammatory Tissue

Abstract Damage to intestinal epithelial cells and the induction of cellular apoptosis are characteristics of inflammatory bowel disease. The C-type lectin receptor family member LSECtin promotes apoptotic cell clearance by macrophages and induces the production of anti-inflammatory/tissue growth factors, which direct intestinal repair in experimental colitis. However, the mechanisms by which the phagocytosis of apoptotic cells triggers the pro-repair function of macrophages remain largely undefined. Here, using immunoprecipitation in combination with mass spectrometry to identify LSECtin-interacting proteins, we found that LSECtin interacted with mTOR, exhibiting a role in activating mTORC1. Mechanistically, apoptotic cells enhance the interaction between LSECtin and mTOR, and increase the activation of mTORC1 induced by LSECtin in macrophages. Elevated mTORC1 signaling triggers macrophages to produce anti-inflammatory/tissue growth factors that contribute to the proliferation of epithelial cells and promote the reestablishment of tissue homeostasis. Collectively, our findings suggest that LSECtin-dependent apoptotic cell clearance by macrophages activates mTORC1, and thus contributes to intestinal regeneration and the remission of colitis.

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Organoid-based modeling of intestinal development, regeneration, and repair

Cell Death and Differentiation ◽

10.1038/s41418-020-00665-z ◽

2020 ◽

Vol 28 (1) ◽

pp. 95-107

Author(s):

Joep Sprangers ◽

Irene C. Zaalberg ◽

Madelon M. Maurice

Keyword(s):

Epithelial Cells ◽

Signaling Pathways ◽

Intestinal Epithelium ◽

Tissue Remodeling ◽

Intestinal Development ◽

Regenerative Response ◽

Key Players ◽

Intestinal Repair ◽

Homeostatic State

AbstractThe intestinal epithelium harbors a remarkable adaptability to undergo injury-induced repair. A key part of the regenerative response is the transient reprogramming of epithelial cells into a fetal-like state, which drives uniform proliferation, tissue remodeling, and subsequent restoration of the homeostatic state. In this review, we discuss how Wnt and YAP signaling pathways control the intestinal repair response and the transitioning of cell states, in comparison with the process of intestinal development. Furthermore, we highlight how organoid-based applications have contributed to the characterization of the mechanistic principles and key players that guide these developmental and regenerative events.

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