The development of an extended normothermicex vivoreperfusion model of the sheep uterus to evaluate organ quality after cold ischemia in relation to uterus transplantation
| Autor: | Mats Brännström, Mihai Oltean, Arvind Manikantan Padma, MyLan Truong, Mats Hellström, Min J. Song, Tagrid Jar‐Allah |
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| Rok vydání: | 2019 |
| Předmět: |
Organ Preservation Solutions
Ischemia Uterus Endometrium Andrology 03 medical and health sciences 0302 clinical medicine Uterus transplantation Animals Medicine 030212 general & internal medicine Sheep 030219 obstetrics & reproductive medicine business.industry Cold Ischemia Obstetrics and Gynecology Organ Preservation General Medicine medicine.disease Transplantation Disease Models Animal medicine.anatomical_structure Reperfusion Injury Reperfusion Female business Reperfusion injury Perfusion Ex vivo |
| Zdroj: | Acta Obstetricia et Gynecologica Scandinavica. 98:1127-1138 |
| ISSN: | 1600-0412 0001-6349 |
| Popis: | Introduction Uterus transplantation has recently proved that infertility in women with uterine factor infertility can be cured. It is still an experimental procedure with numerous critical details remaining to be established, including tolerance to warm and cold ischemic insults. In preparation for human uterus transplantation trials, most teams use the sheep as a model system for research and team training, since the vasculature and the uterus is of similar size as in the human. We, therefore, aimed to develop an ex vivo sheep uterus reperfusion platform that mimics the reperfusion situation so that initial assessments and comparisons can be performed without the need for costly and labor-intensive in vivo transplantation experiments. Material and methods Isolated sheep uteri were perfused with the preservation solution IGL-1 and were then exposed to cold ischemia for either 4 (n = 6) or 48 hours (n = 7). Uteri were then reperfused for 48 hours under normothermic conditions with an oxygenated recirculating perfusate containing growth factors and synthetic oxygen carriers. Histological and biochemical analysis of the perfusate was conducted to assess reperfusion injury. Results Quantification of cell density indicated no significant edema in the myometrium or in the endometrium of uteri exposed to 4 hours cold ischemia and then a normothermic ex vivo reperfusion for 48 hours. Only the outer serosa layer and the inner columnar luminal epithelial cells were affected by the reperfusion. However, a much faster and severe reperfusion damage of all uterine layers were evident during the reperfusion experiment following 48 hours of cold ischemia. This was indicated by major accumulation of extracellular fluid, presence of apoptotic-labeled glandular epithelial layer and vascular endothelium. A significant accumulation of lactate was measured in the perfusate with a subsequent decrease in pH. Conclusions We developed a novel ex vivo sheep uterus model for prolonged perfusion. This model proved to be able to distinguish reperfusion injury-related differences associated to organ preservation. The experimental setup is a platform that can be used to conduct further studies on uterine ischemia- and reperfusion injury that may lead to improved human uterus transplantation protocols. |
| Databáze: | OpenAIRE |
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