Local growth factors are beneficial for the autonomic reinnervation of transplanted islets in rats.
BACKGROUND
Transplanted islets, being avascular and denervated, receive blood vessels and nerves from the recipient. Reinnervation may account in part for the normalization of islet function in islet transplants. Whether reinnervation is possible to augment is not known.


OBJECTIVE
To explore whether reinnervation of transplanted islets is augmented by local addition of growth factors to the graft, syngeneic islets were transplanted to the pancreas of streptozotocin-diabetic Lewis rats with or without pellets locally releasing nerve growth factor (NGF) and vascular endothelial growth factor (VEGF), alone or in combination. The pellets released growth factors for 14 days at a rate of 20 ng/day. After 7 weeks, pancreatic tissue was processed for immunofluorescence of insulin and the neural markers neuropeptide Y (NPY) and tyrosine hydroxylase (TH).


RESULTS
Islets were larger and more numerous after treatment with NGF (p = 0.024) and with NGF in combination with VEGF (p = 0.044). Similarly, immunostaining for TH and the C-terminal flanking peptide of NPY (C-PON) was more pronounced after treatment with NGF in combination with VEGF than in controls (both p < 0.05).


CONCLUSIONS
Local growth factor treatment has a beneficial effect on autonomic reinnervation as well as islet integrity and survival of the graft after islet transplantation in rats.
Reimer
Martina Kvist
MK
Departments of Medicine, Biomedical Center, Lund University, Lund, Sweden.
Mokshagundam
Sri Prakash
SP
Wyler
Karen
K
Sundler
Frank
F
Ahrén
Bo
B
Stagner
John I
JI
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000601:surgery; D005215:Fasting; D007328:Insulin / Q000032:analysis; D007515:Islets of Langerhans / Q000737:chemistry / Q000187:drug effects* / Q000294:innervation; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009478:Neuropeptide Y / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D009478:Neuropeptide Y; D042461:Vascular Endothelial Growth Factor A; D020932:Nerve Growth Factor; D014446:Tyrosine 3-Monooxygenase