The mother of a gut cell: Intestinal epithelial stem cells

Journal of Equine Veterinary Science

2017

All species, including horses, suffer from alterations that increase intestinal permeability. These alterations, also known as “leaky gut,” may lead to severe disease as the normal intestinal barrier becomes compromised and can no longer protect against harmful luminal contents including microbial toxins and pathogens. Leaky gut results from a variety of conditions including physical stressors, decreased blood flow to the intestine, inflammatory disease, and pathogenic infections, among others. Several testing methods exist to diagnose these alterations in both a clinical and research setting. To date, most research has focused on regulation of the host immune response due to the wide variety of factors that can potentially influence the intestinal barrier. This article serves to review the normal intestinal barrier, measurement of barrier permeability, pathogenesis and main causes of altered permeability, and highlight potential alternative therapies of leaky gut in horses while relating what has been studied in other species. Conditions resulting in barrier dysfunction and leaky gut can be a major cause of decreased performance and also death in horses. A better understanding of the intestinal barrier in disease and ways to optimize the function of this barrier is vital to the long-term health and maintenance of these animals.

“…The small intestinal epithelium is composed of villi that extend into the lumen and are lined by differentiated, post-mitotic cell types, and the crypts of Lieberkühn that contain Paneth cells and undifferentiated stem cells [16]. The stem cells are responsible for creating new epithelium every 5–7 days [17,18]. Enteroendocrine, goblet and Paneth cells are the specialized, secretory epithelial cells that maintain the digestive or barrier function of the epithelium via hormone, mucin, and antimicrobial peptide secretion, respectively [13].…”

Section: Intestinal Barrier and Permeabilitymentioning

confidence: 99%

Alterations in Intestinal Permeability: The Role of the “Leaky Gut” in Health and Disease

Stewart

Pratt-Phillips

Journal of Equine Veterinary Science

2017

“…The small intestinal epithelium is composed of villi that extend into the lumen and are lined by differentiated, post-mitotic cell types, and the crypts of Lieberkühn that contain undifferentiated stem cells interspersed with Paneth cells and partially-differentiated transit amplifying cells [3]. Current literature proposes two populations of intestinal stem cells that co-exist in the crypt base including (1) active crypt base columnar cells and (2) reserve/quiescent stem cells that are activated upon injury and preferentially reside at a position four cells above the crypt base [4,5]. The intestinal stem cells are responsible for creating a new epithelial mucosal lining every 5–7 days and only differentiate into cells of intestinal epithelial lineage, unlike mesenchymal stem cells that can give rise to multiple tissue types [4,6].…”

Section: Introductionmentioning

confidence: 99%

Advanced three‐dimensional culture of equine intestinal epithelial stem cells

Stewart

Freund

Equine Veterinary Journal

2017

Self Cite

“…These cells are responsible for homeostatic renewal of the luminal epithelium every 5-7 days. 16 This rapid and ongoing renewal process maintains an intact epithelial lining which serves as a barrier to protect the systemic vasculature from noxious luminal contents. 17,18 In strangulating lesions, barrier compromise occurs when small intestinal blood supply is reduced, leading to progressive epithelial cell loss.…”

Section: Introductionmentioning

confidence: 99%

“…One potential measurement of intestinal epithelial viability is assessment of intestinal epithelial stem cells (ISCs). These cells are responsible for homeostatic renewal of the luminal epithelium every 5–7 days 16 . This rapid and ongoing renewal process maintains an intact epithelial lining which serves as a barrier to protect the systemic vasculature from noxious luminal contents 17,18 .…”

Section: Introductionmentioning

confidence: 99%

Changes in equine intestinal stem/progenitor cell number at resection margins in cases of small intestinal strangulation

Veerasammy

Equine Veterinary Journal

Báez-Ramos

et al. 2023

BackgroundIntestinal epithelial stem cells (ISC) are responsible for epithelial regeneration and are critical to the intestine's ability to regain barrier function following injury. Evaluating ISC biomarker expression in cases of small intestinal strangulation (SIS) may provide insight into clinical progression.ObjectivesIntestinal resection margins from cases of SIS were evaluated to determine if (1) evidence of injury could be identified using histomorphometry, (2) ISC biomarker expression was decreased in the proximal resection margin compared to control and distal resection margin, and (3) the ISC biomarker expression was associated with the number of preoperative risk factors negatively related to outcome, post‐operative complications, or case outcome.Study designRetrospective cohort study.MethodsIntestinal samples were obtained intraoperatively from resection margins of adult horses with SIS and horses euthanised for reasons unrelated to colic. Preoperative risk factors negatively related to outcome, post‐operative complications, and case outcome were obtained from medical records. Horses were grouped as euthanised intraoperatively, postoperatively, or survived to discharge. Histomorphometry and immunofluorescence were performed to evaluate tissue architecture and ISC and progenitor cell number. Groups were compared using one‐way ANOVA. Associations between biomarker expression and the number of preoperative risk factors and post‐operative complications negatively related to outcome were determined using linear regression modelling.ResultsThirty‐six cases of SIS were evaluated. Ki67+ cell counts were decreased in the proximal (mean = 15.45 cells; 95% CI = 10.27–20.63; SD = 4.17; p = 0.02) and distal resection margins (mean = 15.05; 95% CI = 8.46–21.64; SD = 4.141; p = 0.03) in horses euthanised postoperatively compared to control (mean = 23.62 cells; 95% CI = 19.42–27.83; SD = 5.883). In the distal resection margin, an increase in SOX9+Ki67+ cells were associated with a decrease in the total number of preoperative risk factors negatively related to outcome (95% CI = 0.236–1.123; p = 0.008, SE = 0.1393).Main limitationsSmall population size.ConclusionsProliferating cell and ISC numbers may be associated with case outcome.