Abstract
Intestinal transplantation (ITx), the standard treatment for people with intestinal failure that fail to improve with total parenteral nutrition, has low mid- and long-term survival rates in comparison to other solid organ transplantations. The intestine is permanently challenged from without (luminal content) and within (donor's and recipient's immune systems), leading to mucosal damage, breaking the barrier between content and organ. This may cause serious infections and inappropriate immune reactions which result in episodes of sepsis and rejection, respectively. This thesis presents research on the effects of intestinal-specific treatments during the donation process and rejection episodes which aim to improve graft survival.
SECTION A focuses on the effect of preservation of the organ and its barrier function through the enteral application of a preservation solution (luminal preservation, LP) during procurement, storage and engraftment. LP is tested in a rat model developed to understand this therapy in the context of brain death. A human study applies the method in a real-life setting to assess the effects of LP in suitable intestine donors. A pig model of luminal oxygenation during engraftment investigates the use of LP during the last phase of the surgical procedure in the recipient.
SECTION B focuses on the management of different forms of ITx rejection. A review of the immune mechanisms involved in ITx provides the rationale for the use of vedolizumab, a gut-migration blocker, to successfully treat two patients with different forms of rejection (acute cellular and chronic). This is described in two separate case reports and in an encompassing RNA sequencing study of samples taken before and after treatment.
This thesis proposes organ-specific interventions encompassing all phases of the intestinal graft's journey before and after it reaches the recipient. Nuances of these interventions are presented and analysed to find new ways to improve graft survival.
SECTION A focuses on the effect of preservation of the organ and its barrier function through the enteral application of a preservation solution (luminal preservation, LP) during procurement, storage and engraftment. LP is tested in a rat model developed to understand this therapy in the context of brain death. A human study applies the method in a real-life setting to assess the effects of LP in suitable intestine donors. A pig model of luminal oxygenation during engraftment investigates the use of LP during the last phase of the surgical procedure in the recipient.
SECTION B focuses on the management of different forms of ITx rejection. A review of the immune mechanisms involved in ITx provides the rationale for the use of vedolizumab, a gut-migration blocker, to successfully treat two patients with different forms of rejection (acute cellular and chronic). This is described in two separate case reports and in an encompassing RNA sequencing study of samples taken before and after treatment.
This thesis proposes organ-specific interventions encompassing all phases of the intestinal graft's journey before and after it reaches the recipient. Nuances of these interventions are presented and analysed to find new ways to improve graft survival.
| Original language | English |
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| Qualification | Doctor of Philosophy |
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| Award date | 11-May-2022 |
| Place of Publication | [Groningen] |
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| Print ISBNs | 978-94-6361-680-5 |
| Electronic ISBNs | 978-94-6361-681-2 |
| DOIs | |
| Publication status | Published - 2022 |