Clinical and experimental pancreatic islet transplantation to striated muscle: establishment of a vascular system similar to that in native islets.
OBJECTIVE
Curing type 1 diabetes by transplanting pancreatic islets into the liver is associated with poor long-term outcome and graft failure at least partly due to inadequate graft revascularization. The aim of the current study was to evaluate striated muscle as a potential angiogenic site for islet transplantation.


METHODS
The current study presents a new experimental model that is found to be applicable to clinical islet transplantation. Islets were implanted into striated muscle and intraislet vascular density and blood flow were visualized with intravital and confocal microscopy in mice and by magnetic resonance imaging in three autotransplanted pancreatectomized patients. Mice were rendered neutropenic by repeated injections of Gr-1 antibody, and diabetes was induced by alloxan treatment.


RESULTS
Contrary to liver-engrafted islets, islets transplanted to mouse muscle were revascularized with vessel densities and blood flow entirely comparable with those of islets within intact pancreas. Initiation of islet revascularization at the muscular site was dependent on neutrophils, and the function of islets transplanted to muscle was proven by curing diabetic mice. The experimental data were confirmed in autotransplanted patients where higher plasma volumes were measured in islets engrafted in forearm muscle compared with adjacent muscle tissue through high-resolution magnetic resonance imaging.


CONCLUSIONS
This study presents a novel paradigm in islet transplantation whereby recruited neutrophils are crucial for the functionally restored intraislet blood perfusion following transplantation to striated muscle under experimental and clinical situations.
Christoffersson
Gustaf
G
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Henriksnäs
Johanna
J
Johansson
Lars
L
Rolny
Charlotte
C
Ahlström
Håkan
H
Caballero-Corbalan
José
J
Segersvärd
Ralf
R
Permert
Johan
J
Korsgren
Olle
O
Carlsson
Per-Ola
PO
Phillipson
Mia
M
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002469:Cell Separation; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000601:surgery*; D007515:Islets of Langerhans / Q000098:blood supply* / Q000166:cytology / Q000502:physiology; D016381:Islets of Langerhans Transplantation / Q000379:methods / Q000502:physiology*; D047589:Leukocyte Reduction Procedures / Q000379:methods; D007962:Leukocytes / Q000166:cytology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D018482:Muscle, Skeletal / Q000098:blood supply / Q000502:physiology*; D009504:Neutrophils / Q000166:cytology / Q000502:physiology; D009924:Organ Culture Techniques; D012086:Reoperation; D014182:Transplantation, Autologous; D016042:Transplantation, Heterotopic / Q000379:methods*
D001786:Blood Glucose; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate