Abstract
The liver has the unique capacity to fully regenerate after surgical removal of part of the liver or after major injury by for example toxins. The regenerative capacity of the liver allows for surgical removal of up to 70% of the liver volume, which may be required in patients with cancer. However, in some patients liver regeneration fails and patients may die from liver insufficiency as limited therapeutic options in such patients are currently available. Therefore, new therapeutic options to stimulate liver regeneration are of considerable interest. Blood platelets are well known for their role in cessation of bleeding, but have a recently described unexpected role in liver regeneration. However, the molecular mechanisms underlying platelet-mediated stimulation of liver regeneration are unclear.
This thesis decribes the results of several in vitro and in vivo studies in which mechanisms underlying platelet-mediated liver regeneration were investigated. Currently it is widely assumed that certain proteins (growth factors) stored within platelets drive liver regeneration. However, in a prospective clinical study we found no evidence for a role of these proteins for liver regeneration in humans. We did elucidate a unique new mechanism by which platelets stimulate growth of liver cells. Specifically, we have found that platelets, a cell that lacks a nucleus (and consequently DNA), transfers genetic material (RNA) to liver cells, which in turn translate this RNA to protein. We demonstrated that this RNA transfer is key in stimulation of liver cells by platelets. Additionally, we used in vivo models to visualize platelet interactions with the regenerating liver. These studies identified a key molecule involved in platelet recruitment to the regenerating liver and the regenerative process itself.
The studies described in this thesis have resulted in a better understanding on the mechanism underlying platelet-mediated stimulation of liver regeneration, and have identified potential therapeutic targets.
This thesis decribes the results of several in vitro and in vivo studies in which mechanisms underlying platelet-mediated liver regeneration were investigated. Currently it is widely assumed that certain proteins (growth factors) stored within platelets drive liver regeneration. However, in a prospective clinical study we found no evidence for a role of these proteins for liver regeneration in humans. We did elucidate a unique new mechanism by which platelets stimulate growth of liver cells. Specifically, we have found that platelets, a cell that lacks a nucleus (and consequently DNA), transfers genetic material (RNA) to liver cells, which in turn translate this RNA to protein. We demonstrated that this RNA transfer is key in stimulation of liver cells by platelets. Additionally, we used in vivo models to visualize platelet interactions with the regenerating liver. These studies identified a key molecule involved in platelet recruitment to the regenerating liver and the regenerative process itself.
The studies described in this thesis have resulted in a better understanding on the mechanism underlying platelet-mediated stimulation of liver regeneration, and have identified potential therapeutic targets.
| Original language | English |
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| Qualification | Doctor of Philosophy |
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| Supervisors/Advisors |
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| Award date | 4-Oct-2017 |
| Place of Publication | [Groningen] |
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| Print ISBNs | 978-94-92679-10-9 |
| Publication status | Published - 2017 |