Bioartificial pancreas transplantation at prevascularized intermuscular space: effect of angiogenesis induction on islet survival.
BACKGROUND
Bioartificial pancreas (BAP) transplantation offers a potential treatment of diabetes mellitus. The optimal site for BAP transplantation has not yet been established.


OBJECTIVE
To monitor the effect of induction of neovascularization at the intermuscular space on islet survival after allogenic transplantation of BAP.


METHODS
Angiogenesis was induced at the intermuscular space of diabetic Lewis rats by implanting a polyethylene terephthalate (PET) mesh bag, which enclosed a collagen sponge and biodegradable gelatin microspheres containing basic fibroblast growth factor. After confirmation of angiogenesis, BAP was prepared by mixing of 5% agarose with approximately 2,800 isolated rat (Sprague-Dawley) islets and transplanted into the prevascularized PET mesh bag.


RESULTS
Neovascularization was observed in and around the PET mesh bag within 10 days after implantation as confirmed by macroscopic and microscopic examinations. In the presence of a collagen sponge, new blood vessels penetrated into the PET mesh bag and formed a vascular bed. After transplantation, normoglycemia was achieved in the rats within 3 days and maintained for >35 days. The rats gradually gained body weight, and the results of intravenous glucose tolerance test showed normal patterns of blood glucose clearance 1 month after transplantation.


CONCLUSIONS
It can be concluded that the prevascularized PET mesh bag enabled transplanted BAP to survive and maintain function, thus indicating a potential site for BAP transplantation.
Balamurugan
A N
AN
Department of Organ Reconstruction, Field of Clinical Application, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
Gu
Yuanjun
Y
Tabata
Yasuhiko
Y
Miyamoto
Masaaki
M
Cui
Wanxing
W
Hori
Hiroshi
H
Satake
Akira
A
Nagata
Natsuki
N
Wang
Wenjing
W
Inoue
Kazutomo
K
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D002470:Cell Survival / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005951:Glucose Tolerance Test; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D018919:Neovascularization, Physiologic; D010179:Pancreas / Q000098:blood supply* / Q000187:drug effects; D019397:Pancreas, Artificial; D011093:Polyethylene Terephthalates; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D011093:Polyethylene Terephthalates; D016222:Fibroblast Growth Factor 2