Inadequate vascularization and microvascular rejection are major limit
ations for successful free pancreatic islet xenotransplantation, Commo
nly used immunosuppressive regimens may alter the process of vasculari
zation, and are ineffective at preventing graft rejection, In this stu
dy, we investigated, in vivo, the action of the new immunosuppressive
agent RS-61443 on angiogenesis and microvascular rejection of rat panc
reatic islets after xenogeneic transplantation into the dorsal skinfol
d of Syrian golden hamsters, In nontreated xenografts, intravital fluo
rescence microscopy demonstrated a regular process of vascularization
during the first 6 days after transplantation. On days 10, 14, and 20,
graft rejection was observed, characterized by microvascular leukocyt
e accumulation (244+/-59 mm(-2)), loss of endothelial integrity, and c
apillary perfusion failure, Islet xenografts of animals treated with R
S-61443 (40 mg/kg per day) demonstrated inhibition of vascularization
with the consequence of a markedly reduced size of the grafts' microva
scular network (0.05 +/- 0.007 mm(2)), when compared with that of nont
reated xenografts (0.09 +/- 0.015 mm(2); P<0.05). However, treatment w
ith RS-61443 effectively prevented microvascular graft rejection, as i
ndicated by the absence of leukocyte accumulation (24+/-9 mm(-2); P <
0.01), endothelial damage, and nutritive perfusion failure, Thus, RS-6
1443 treatment may represent an interesting approach for improving the
outcome of pancreatic islet xenotransplantation.