Pancreatic acellular matrix supports islet survival and function in a synthetic tubular device: in vitro and in vivo studies.
Increasing pancreatic islet survival and function is a starting point for obtaining a valuable bioartificial pancreas for the treatment of type 1 diabetes. In this context, decellularized matrices, obtained after the removal of tissue cellular part, are known to support in vitro adhesion, growth, and function of several cell types. We demonstrate that a homologous acellular pancreatic matrix is a suitable scaffold for rat islet cultures maintaining their long-term viability and function. Islets adhered to the pancreatic matrix showed a constant glucose-induced insulin release during long-term in vitro incubation, while islets cultured without a matrix or on the liver matrix showed a progressive reduction. In order to obtain implantable devices, acellular matrix/islet cultures were entrapped into poly(vinyl alcohol) (PVA)/ poly(ethylene glycol) (PEG) tubes obtained by the freezing/thawing procedure. Under this condition, an in vitro constant insulin release was detected. The devices were then implanted into diabetic rats where reduced insulin requirement was noted suggesting insulin secretory activity of islets contained in the device. Indeed, immunofluorescence confirmed the presence of insulin- and glucagon-producing cells into the explanted devices. These data show that PVA/PEG semi-permeable membrane can obtain devices that restore, at least in part, insulin secretion.
De Carlo
E
E
Clinica Medica III, Hospital/University of Padova, I-35128 Padova, Italy. euge.decarlo@tiscali.it
Baiguera
S
S
Conconi
M T
MT
Vigolo
S
S
Grandi
C
C
Lora
S
S
Martini
C
C
Maffei
P
P
Tamagno
G
G
Vettor
R
R
Sicolo
N
N
Parnigotto
P P
PP
D000704:Analysis of Variance; D000818:Animals; D019149:Bioreactors; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D005109:Extracellular Matrix / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism; D008297:Male; D008855:Microscopy, Electron, Scanning; D011092:Polyethylene Glycols; D011142:Polyvinyl Alcohol; D051381:Rats; D017208:Rats, Wistar; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods*; D054457:Tissue Scaffolds
D007328:Insulin; D011092:Polyethylene Glycols; D011142:Polyvinyl Alcohol; D005947:Glucose