Blodkärl består inte enbart av de endotelceller som är närmast blodbanan.
Beroende på var i kroppen blodkärlet befinner sig och hur stort det är består det även av bl.a. fibrös vävnad, glatt muskulatur och nerver. En celltyp som är en viktig del av blodkärlen är pericyten. Den sitter precis utanpå endotel-cellerna och delar basalmembran med dessa. Pericyter bidrar med både fy-sisk stabilitet och utsöndrar substanser som håller endotelcellerna i ett stabilt tillstånd.
Kärlnätverket i Langerhanska cellöar har en god täckning av pericyter, men det har varit oklart om de återkommer efter transplantation. Efter transplan-tation till muskel hos mus i studie IV återkommer pericyterna i ungefär samma takt som blodkärlen och efter fyra veckor är de nybildade kärlen helt täckta med pericyter. Makrofagerna i studie III antog platser väldigt nära blodkärlen, på ett sätt som liknade pericyters vis. Detta föranledde en under-sökning kring hur dessa två celltyper är kopplade till varandra.
Hos möss som saknade makrofager undersöktes pericyttäckningen av blodkärlen i transplanterade cellöar. Dessa hade mycket färre pericyter än möss som hade normalt makrofagantal. I en mus som har grönfluorescerande makrofager upptäcktes att dessa även uttryckte den pericytspecifika markö-ren NG2.
I transplanterade Langerhanska cellöar har alltså makrofager en stor in-verkan på rekryteringen av nya pericyter. Vissa makrofager uttrycker pericytspecifika markörer, vilket kan innebära att makrofager i transplante-rade cellöar kan övergå till att bli pericyter.
Slutsats
Genom att transplantera Langerhanska cellöar till muskel kan blodkärlsnät-verket återupprättas och funktionen förbättras, något som kan leda till effek-tivare transplantationer för diabetiker framöver. Den experimentella modell som togs fram för att studera angiogenes möjliggjorde studier av immuncel-lers påverkan på blodkärlstillväxten. En särskild typ av immuncell som var involverad i detta identifierades och nya kopplingar mellan immunceller och de celler som utgör blodkärlen upptäcktes.
Acknowledgements
The majority of the work presented in this thesis was carried out at the De-partment of Medical Cell Biology, Uppsala University, Sweden. The results in here were not the work of one person alone; therefore I would like to ex-press my gratitude to:
My supervisor Associate Professor Mia Phillipson, for taking me on as your first PhD student in this exciting project. The way you not only work to get great scientific results, but also mentor your students to grow into better scientists is truly admirable. Working with you during these years, not only producing data, but also building a new lab, has been a blast!
My co-supervisor Professor Per-Ola Carlsson, for being the link to the clin-ic, for doing things faster than anyone else, for being a fellow smålänning, and an overall scientific role model.
My co-supervisor Professor Leif Jansson, who was the one who trusted me with a summer project as an undergrad many years ago, for lighting an inter-est in research and for continuing to be an inspiration in science and trivia.
My co-supervisor Dr Johanna Henriksnäs, who was the one to pioneer the field of curing diabetes through the cremaster muscle, for your enthusiasm, and for introducing me to lab things like anesthesia and rodent-MRI, and other things like the unexpectedly vast diversity of jelly beans.
All co-authors to the studies.
The heads of the department, present and former: Professor Erik Gylfe, and Professor Arne Andersson.
The technical assistance and overall guidance from Astrid Nordin, Lisbeth Sagulin, Anders Ahlander, Marianne Ljungkvist, IngBritt Hallgren, Ing-Marie Mörsare, and Eva Törnelius have been extremely valuable.
The animal facility staff for taking good care of my mice and the breeding of the B6.129P-Cx3cr1tm1Litt/J…äh, the cages with the purple tags!
The guys from the hospital: Dr José Caballero-Corbalàn, Dr Lars Johans-son, and Professor Olle Korsgren.
The Belgians: Professor Ghislain Opdenakker, Jennifer Vandooren, and your Rega-colleagues for a scientifically fruitful collaboration, and a won-derful time in Leuven.
The Americans: Professor Alvin Powers, Dr Marcela Brissova, and Rachel Reinert for excellent help on VEGF and islets.
The Canadians: All people in the Kubes lab for very rewarding periods in Calgary.
The guys at BioVis: Pacho, Matyas, and Jan.
The research group of Phillipson and Holm; Lena, for letting me “piggy-back” on the GI-group in the beginning, and for creating a nice atmosphere in the lab. Ulrika, for great times in- and outside of the lab, in and out of avalanche country, and for always letting me sit in the therapy-chair when needed. Evelina, for all help in the lab, for extreme and contagious enthusi-asm, and for sharing an interest in things that are hard (like flow cytometry and skiing). Sara, for once doubling the size of the lab and being my first lab mate. David, for discussions about everything from CX3CR1 to CMOS. To-mas, for introducing cleanliness to the lab with “your” bench. Antoine, for putting up with my impossible (?) experiments, and for being witty. Magnus, for the non-biologist angle to things. Annika, for always helping out, and for keeping the lab together. Cecilia, for coming to the lab now and then to turn up the pace. Former members Olof and Joel, for setting an atmosphere that I think still lives.
The persons helping out with economy, teaching, and technical issues at the department: Camilla, Shumin, Agneta, Gunno, Erik, Oleg, Göran, Lina, and Björn.
The faculty at the department for discussions, feedback, and sharing of methods and materials. Special thanks to Professor Michael Welsh, and Pro-fessor Nils Welsh.
Former and present PhD students and post-docs at the department, in par-ticular: Andreas, Daniel, Daniela, Ebba, Guang, Joey, Johan, Johan, Karin, Liselotte, Liza, Malou, Marie, Mattias, Michael, Patrik, Rikard, Sara, Sara, Sara, Stephanie, Xiang, and Åsa for great assistance, seminars, parties, lunches, and endless coffee breaks.
All people at the department for making the three corridors a very nice place to work. A special thanks to Angelica for your help with a wide range of things (from labware to coffee machines).
All students that have been involved in the projects.
Alla vänner utanför labbet som dragit ut mig från BMC för att göra något helt annat.
Erik för att ha introducerat mig till uthållighetssportens underbara och smärt-samma värld – det har varit en ventil i skrivandet. Arvid, Amelie och Johan för luncher, spex och mycket annat.
Klas, Kristofer, Mattias och Henrik, för allt vi gjort och allt vi fortsätter att göra. Killar kan!
Hedvig, för att du är en så bra vän (och för att en del av denna avhandling skrevs på din soffa).
Min familj: mamma Gunilla, pappa Jan-Ove, bror Filip, syster Amalia och farmor Inga-Britt. För att ni är grunden till allt.
Annika, för att du visar mig det viktiga i livet. Jag älskar dig!
The work in this thesis was supported by the Swedish Research Council, the Knut & Alice Wallenberg Foundation, the Swedish Diabetes Associa-tion, the Novo Nordisk FoundaAssocia-tion, the Ragnar Söderberg FoundaAssocia-tion, the Clas Groschinsky Foundation, the Jeansson Foundation, the Mag-nus Bergvall Foundation, the Lars Hierta Foundation, the Thuring Founda-tion, the Family Ernfors FoundaFounda-tion, the Åke Wiberg FoundaFounda-tion, the Anér Foundation, the Swedish Diabetes Foundation, the Juvenile Diabetes Re-search Foundation, and The Royal Swedish Academy of Sciences.
Jag vill personligen tacka Anna Maria Lundins stipendiefond vid Små-lands nation i Uppsala samt Gunnar Hylténs stiftelse vid Apotekarsocieteten för stipendier som möjliggjort vistelser vid utländska universitet och konfe-rensresor.
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