1. Tissue Eng Part A. 2010 May;16(5):1503-13.

In vivo selection of biocompatible alginates for islet encapsulation and
subcutaneous transplantation.

Vériter S, Mergen J, Goebbels RM, Aouassar N, Grégoire C, Jordan B, Levêque P,
Gallez B, Gianello P, Dufrane D.

Laboratory of Experimental Surgery, Université Catholique de Louvain, Faculté de 
Médecine, Brussels, Belgium.

Islet encapsulation requires several properties including (1) biocompatibility,
(2) immunoprotection, and (3) oxygen diffusion for islet survival and diabetes
correction. New chemical alginates were tested in vivo and compared with
traditional high-mannuronate and -guluronate alginates. New alginates with
coupled peptide sequence (sterile lyophilized high mannuronate [SLM]-RGD3% and
sterile lyophilized high guluronate [SLG]-RGD3%), to improve encapsulated cell
adherence in the matrix, and alginates with a very low viscosity (VLDM7% and
VLDG7%), to reduce implant size by loading a higher number of islets per volume
of polymer, were implanted subcutaneously in 70 Wistar rats for comparison with
alginates of high viscosity and high content of mannuronic (SLM3%) or guluronic
acids (SLG3%). Permeability of alginates to 36-, 75-, and 150-kDa lectins coupled
to fluorescein isothiocynate was quantified before implantation and at 2, 4, and 
12 weeks after implantation. Biocompatibility (fibrosis, graft stability,
immunologic infiltration by CD3/CD68 cells, and neovascularization) was assessed 
at each explantation time. Permeability to small molecules was found for all
alginates. Impermeability to 150-kDa molecules, such as IgG, was observed only
for SLM3% before implantation and was maintained up to 12 weeks after
implantation. SLM3% and SLG3% demonstrated better graft stability with lower
CD3/CD68 recruitment and fibrosis than the other alginates. SLM3% induced a
significantly higher angiogenesis and maintained oxygen pressure at approximately
40 mm Hg for up to 4 weeks after implantation as measured by in vivo electronic
paramagnetic resonance oximetry. SLM-encapsulated pig islets implanted
subcutaneously in rats demonstrated no inflammatory/immunologic reactions and
islets functioned for up to 60 days without immunosuppression. A traditional
alginate made of high mannuronic content (SLM3%) is an adapted material to
immunoprotect islets in subcutaneous tissue. No improvement was found with lower 
viscosity and use of GRGDSP-peptide sequence.


PMID: 20001535 [PubMed - indexed for MEDLINE]