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Role of Thrombospon...
Role of Thrombospondin-1 in Endogenous and Transplanted Pancreatic Islets
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- Olerud, Johan, 1977- (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi,Per-Ola Carlsson
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- Carlsson, Per-Ola, MD, PhD (thesis advisor)
- Uppsala universitet,Institutionen för medicinsk cellbiologi,Medicin
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- Welsh, Nils, Professor (thesis advisor)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Jansson, Leif, Professor (thesis advisor)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Berney, Thierry, Professor (opponent)
- University Medical Center, Geneva
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(creator_code:org_t)
- ISBN 9789155474652
- Uppsala : Acta Universitatis Upsaliensis, 2009
- English 57 s.
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Series: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 436
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https://uu.diva-port... (primary) (Raw object)
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Abstract
Subject headings
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- Type 1 diabetes mellitus is a severe life-long disease with a pronounced risk of developing secondary complications. One way to avoid the latter is to restore the fine tuning of blood glucose homeostasis by transplantation of pancreatic islets. However, isolated islets need to be properly engrafted and to re-establish a vascular network in order to regain function. Earlier studies have shown that pancreatic islets experimentally transplanted to e.g. the liver or the kidney become poorly revascularized. In the present thesis, mice deficient of the angiostatic factor thrombospondin-1 (TSP-1) were found to have an impaired beta-cell function. Development of this beta-cell dysfunction was prevented by treatment of TSP-1 deficient mice from birth with the TGFbeta-1 activating sequence of TSP-1. TSP-1 in islets was predominantly expressed in the endothelial cells. Isolated islet endothelial cells was observed to have a low proliferatory and migratory capacity towards angiogenic stimuli, but this could be reversed by neutralizing antibodies to the angiostatic factors alpha1-antitrypsin, endostatin or TSP-1. Transient downregulation of TSP-1 expression in mouse islet cells prior to transplantation improved graft revascularization, blood perfusion, oxygenation and function when evaluated one-month post-transplantation. The same result was achieved when islets or recipients of islets were pre-treated with the hormone prolactin one-month post-transplantation. The present study illustrates the importance of the angiostatic factor TSP-1 for islet beta-cell function and engraftment of islets following transplantation. Interference with TSP-1 can possibly be used to improve the results of clinical islet transplantation.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Medical cell biology
- Medicinsk cellbiologi
- medicinsk cellbiologi
- Medical Cell Biology
Publication and Content Type
- vet (subject category)
- dok (subject category)
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