Dexamethasone suppresses the expansion and transdifferentiation of transplanted porcine neonatal pancreas cell clusters (NPCCs) into beta-cells in normal nude mice.
OBJECTIVE
This study was performed to investigate the effect of dexamethasone on the expansion and transdifferentiation of transplanted neonatal pancreas cell clusters (NPCCs) in vivo.


METHODS
Porcine NPCCs were generated from 1 to 3-day-old neonatal pigs. After transplantation (Tx) of 4000 islet equivalents (IEqs) of NPCCs beneath the renal subcapsular space of normoglycemic nude mice, dexamethasone (Dx, 1 mg/kg) or vehicles were injected daily. Intraperitoneal glucose tolerance testing (ip-GTT) was performed at 4 weeks (n = 4) and 10 weeks (n = 7) after Tx. After harvesting the grafts, total graft and beta-cell graft mass were determined by morphometric analysis.


RESULTS
Although the mean value of AUCg was elevated in the Dx-treated group at 10 weeks after Tx, the glucose levels of all the animals by ip-GTT were within the normal range. At 10 weeks after Tx, the relative volume, absolute mass of beta-cells in the graft, and total graft mass were significantly lower in the Dx-treated group (relative volume of beta-cells: 22.0% versus 35.3%, P < 0.05; beta-cells mass: 1.0 +/- 1.2 mg versus 2.2 +/- 5.6 mg, P < 0.05, total graft mass: 4.4 +/- 5.4 mg versus 6.3 +/- 1.3 mg, P < 0.05, Dx-treated versus control), but there was no difference at 4 weeks. Morphologically prominent cystic structures were observed in the Dx group at 10 weeks.


CONCLUSIONS
Our results suggest that dexamethasone suppresses the expansion and transdifferentiation of transplanted porcine NPCCs into beta-cells in normal nude mice.
Ko
S-H
SH
Division of Endocrinology and Metabolism, Department of Internal Medicine, The Catholic University of Korea, Kangnam St. Mary's Hospital, #505, Banpo-Dong, Seocho-Gu, Seoul, South Korea.
Kwon
H-S
HS
Suh
S-H
SH
Yang
J-H
JH
Kim
S-R
SR
Ahn
Y-B
YB
Song
K-H
KH
Yoo
S-J
SJ
Son
H-S
HS
Cha
B-Y
BY
Lee
K-W
KW
Son
H-Y
HY
Kang
S-K
SK
Park
C G
CG
Park
J-K
JK
Yoon
K-H
KH
D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D013370:Subrenal Capsule Assay; D013552:Swine; D014183:Transplantation, Heterologous / Q000502:physiology*
D007328:Insulin; D003907:Dexamethasone