Preservation of reserve intestinal epithelial stem cells following severe ischemic injury
| Autor: | John M. Freund, Christopher M. Dekaney, Amy Stieler Stewart, Scott T. Magness, Cecilia Renee Kucera, Liara M. Gonzalez, Anthony T. Blikslager |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Physiology Cell Survival Swine Population Apoptosis Biology Receptors G-Protein-Coupled 03 medical and health sciences 0302 clinical medicine Ischemia Physiology (medical) medicine Animals Cell Self Renewal Intestinal Mucosa education Cell Proliferation Homeodomain Proteins education.field_of_study Hepatology Stem cell population Gastroenterology Ischemic injury Epithelium Disease Models Animal 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Reperfusion Injury Stem cell Research Article |
| Zdroj: | American journal of physiology. Gastrointestinal and liver physiology. 316(4) |
| ISSN: | 1522-1547 |
| Popis: | Intestinal ischemia is an abdominal emergency with a mortality rate >50%, leading to epithelial barrier loss and subsequent sepsis. Epithelial renewal and repair after injury depend on intestinal epithelial stem cells (ISC) that reside within the crypts of Lieberkühn. Two ISC populations critical to epithelial repair have been described: 1) active ISC (aISC; highly proliferative; leucine-rich-repeat-containing G protein-coupled receptor 5 positive, sex determining region Y-box 9 positive) and 2) reserve ISC [rISC; less proliferative; homeodomain only protein X (Hopx)+]. Yorkshire crossbred pigs (8–10 wk old) were subjected to 1–4 h of ischemia and 1 h of reperfusion or recovery by reversible mesenteric vascular occlusion. This study was designed to evaluate whether ISC-expressing biomarkers of aISCs or rISCs show differential resistance to ischemic injury and different contributions to the subsequent repair and regenerative responses. Our data demonstrate that, following 3–4 h ischemic injury, aISC undergo apoptosis, whereas rISC are preserved. Furthermore, these rISC are retained ex vivo in spheroids in which cell populations are enriched in the rISC biomarker Hopx. These cells appear to go on to provide a proliferative pool of cells during the recovery period. Taken together, these data indicate that Hopx+ cells are resistant to injury and are the likely source of epithelial renewal following prolonged ischemic injury. It is therefore possible that targeting reserve stem cells will lead to new therapies for patients with severe intestinal injury. NEW & NOTEWORTHY The population of reserve less-proliferative intestinal epithelial stem cells appears resistant to injury despite severe epithelial cell loss, including that of the active stem cell population, which results from prolonged mesenteric ischemia. These cells can change to an activated state and are likely indispensable to regenerative processes. Reserve stem cell targeted therapies may improve treatment and outcome of patients with ischemic disease. |
| Databáze: | OpenAIRE |
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