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ENDOTHELIAL- EPITHELIAL INTERACTIONS Blood vessels friends or foes?

Wolfhagen Sand, Fredrik LU (2011) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2011:1.
Abstract (Swedish)
Popular Abstract in Swedish

Diabetes är en av de vanligaste folksjukdomarna och tusentals diagnostiseras med sjukdomen varje år. Det finns två typer av diabetes, typ 1 och typ 2. I typ 1 förstörs de insulin producerande β-cellerna som finns i de Langerhanska öarna av kroppens immunförsvar. β-cellerna har till uppgift att reglera blodsockernivåerna. Avsaknaden av egen insulinproduktion leder till diabetes som behandlas med insulininjektioner. Trots kraftigt förbättrade behandlingsmetoder kan vi inte artificiellt reglera blodsocker nivårena lika jämnt som β-cellerna gör. Fluktuationerna av blodsockernivåerna leder på sikt till en mängd komplikationer, bland dem diabetisk retinopati. Diabetisk retinopati är den vanligaste... (More)
Popular Abstract in Swedish

Diabetes är en av de vanligaste folksjukdomarna och tusentals diagnostiseras med sjukdomen varje år. Det finns två typer av diabetes, typ 1 och typ 2. I typ 1 förstörs de insulin producerande β-cellerna som finns i de Langerhanska öarna av kroppens immunförsvar. β-cellerna har till uppgift att reglera blodsockernivåerna. Avsaknaden av egen insulinproduktion leder till diabetes som behandlas med insulininjektioner. Trots kraftigt förbättrade behandlingsmetoder kan vi inte artificiellt reglera blodsocker nivårena lika jämnt som β-cellerna gör. Fluktuationerna av blodsockernivåerna leder på sikt till en mängd komplikationer, bland dem diabetisk retinopati. Diabetisk retinopati är den vanligaste orsaken till blindhet hos den yngre befolkningen.

Både att mildra komplikationerna av diabetes och att hitta behandlingsmetoder för att bota sjukdomen är viktig.

I en musmodell för diabetisk retinopati har vi kunnat visa att avsaknaden av molekylen N-CAM skyddar mot delar av den sjukliga nybildningen av blodkärl som sker hos diabetiker.

Under de senaste 10 åren har forskare visat att det är möjligt att tillfälligt bota diabetes genom att transplantera Langerhanska öar från avlidna donatorer till diabetiker. Transplantationen kräver att immunförsvaret hämmas, vilket kan leda till andra komplikationer. Antalet diabetiker i behov av transplantation är mångt mycket större än tillgången på donatorer.

Att använda stamceller för att ta fram insulinproducerande β-celler skulle kunna vara en möjlig väg. För att kunna få stamcellerna att bilda β-celler är det viktigt att förstå hur dessa celler bildas under fosterutvecklingen. Genom att använda en musmodell har vi kunnat studera hur blodkärl reglerar tillväxten av förstadier till β-cellerna. Vi har även kunnat visa att bildandet av rörsystemet i pankreas är viktigt för vilka celltyper som skall bildas i pankreas. Våra resultat kan användas för att ta fram bättre metoder för att bilda β-celler från stamceller. (Less)
Abstract
Diabetes affects enormous amounts of patients. In type 1 diabetes the insulin producing β cells in the islet of Langerhans are destroyed by the immune system. The β cells, which are located in the pancreas, regulate blood glucose levels. The lack of insulin production requires administration of insulin. This is accomplished by insulin injections. Even though the treatment methods have been improved, we are still not able to artificially regulate the blood glucose levels as evenly as the β cells. The fluctuations of the blood glucose levels results in the long term in a number of complication, among the diabetic retinopathy. Diabetic retinopathy is the leading cause of blindness among the younger population.

Both to reduce the... (More)
Diabetes affects enormous amounts of patients. In type 1 diabetes the insulin producing β cells in the islet of Langerhans are destroyed by the immune system. The β cells, which are located in the pancreas, regulate blood glucose levels. The lack of insulin production requires administration of insulin. This is accomplished by insulin injections. Even though the treatment methods have been improved, we are still not able to artificially regulate the blood glucose levels as evenly as the β cells. The fluctuations of the blood glucose levels results in the long term in a number of complication, among the diabetic retinopathy. Diabetic retinopathy is the leading cause of blindness among the younger population.

Both to reduce the complications of diabetes and to find cures of the disease is important.

By using a model for diabetic retinopathy in mice we have been able to show that lack of the molecule N-CAM is protecting against the pathological neovascularization affecting diabetic patients.

The last 10 years have proven it possible to cure diabetes through transplantations of islets of Langerhans from cadaveric donors. The transplantations requires suppression of the immune response, this could lead to other complications. The amount of diabetic patients in need of transplantations far exceeds the availability of donors.

The use of stem cells to produce insulin producing β cells might be a possible way. To be able to direct the stem cells into β cells it is important to understand how these cells form during embryo development.

By the use of mice we have been able to study how blood vessels regulate the growth of the precursors of β cells. We have also been able to show that the formation of a tubular system in the pancreas is important for the regulation of which cell types that are to be formed.

Our results can be used to develop better methods for the production of β cells from stem cells. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Claesson-Welsh, Lena, Department of Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Sweden
organization
publishing date
type
Thesis
publication status
published
subject
keywords
blood vessels, pancreas, endoderm development, S1P1, N-CAM, diabetic retinopathy, diabetes, tubulogenesis, Cdc42
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2011:1
pages
196 pages
publisher
Stem Cell Center, Lund University
defense location
Belfragesalen BMC D15
defense date
2011-01-07 13:00
ISSN
1652-8220
ISBN
978-91-86671-48-8
language
English
LU publication?
yes
id
3460a5f6-d79d-427a-9564-23ecb6f87686 (old id 1746496)
date added to LUP
2010-12-22 07:41:33
date last changed
2016-09-19 08:44:45
@phdthesis{3460a5f6-d79d-427a-9564-23ecb6f87686,
  abstract     = {Diabetes affects enormous amounts of patients. In type 1 diabetes the insulin producing β cells in the islet of Langerhans are destroyed by the immune system. The β cells, which are located in the pancreas, regulate blood glucose levels. The lack of insulin production requires administration of insulin. This is accomplished by insulin injections. Even though the treatment methods have been improved, we are still not able to artificially regulate the blood glucose levels as evenly as the β cells. The fluctuations of the blood glucose levels results in the long term in a number of complication, among the diabetic retinopathy. Diabetic retinopathy is the leading cause of blindness among the younger population.<br/><br>
Both to reduce the complications of diabetes and to find cures of the disease is important.<br/><br>
By using a model for diabetic retinopathy in mice we have been able to show that lack of the molecule N-CAM is protecting against the pathological neovascularization affecting diabetic patients.<br/><br>
The last 10 years have proven it possible to cure diabetes through transplantations of islets of Langerhans from cadaveric donors. The transplantations requires suppression of the immune response, this could lead to other complications. The amount of diabetic patients in need of transplantations far exceeds the availability of donors.<br/><br>
The use of stem cells to produce insulin producing β cells might be a possible way. To be able to direct the stem cells into β cells it is important to understand how these cells form during embryo development.<br/><br>
By the use of mice we have been able to study how blood vessels regulate the growth of the precursors of β cells. We have also been able to show that the formation of a tubular system in the pancreas is important for the regulation of which cell types that are to be formed.<br/><br>
Our results can be used to develop better methods for the production of β cells from stem cells.},
  author       = {Wolfhagen Sand, Fredrik},
  isbn         = {978-91-86671-48-8},
  issn         = {1652-8220},
  keyword      = {blood vessels,pancreas,endoderm development,S1P1,N-CAM,diabetic retinopathy,diabetes,tubulogenesis,Cdc42},
  language     = {eng},
  pages        = {196},
  publisher    = {Stem Cell Center, Lund University},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {ENDOTHELIAL- EPITHELIAL INTERACTIONS Blood vessels friends or foes?},
  volume       = {2011:1},
  year         = {2011},
}