The capsular overgrowth on microencapsulated pancreatic islet grafts in streptozotocin and autoimmune diabetic rats

Fritschy, Wilbert M.; Vos, Paul De; Groen, Herman; Klatter, Frits A.; Pasma, A.; Wolters, G. H. J.; Schilfgaarde, R. van

doi:10.1007/bf00327154

Cited by 43 publications

(60 citation statements)

References 28 publications

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“…Purification of alginate was performed as described in detail by our group elsewhere [8]. All identified factors influencing biological responses were tested in the present study [5,[8][9][10][11][12][13][14]. The composition of the alginate was studied after purification by nuclear magnetic resonance analysis [8].…”

Section: Alginatesmentioning

confidence: 99%

“…The biological response against capsules was assessed by quantifying the number of capsules overgrown by macrophages and fibroblasts [5,9]. Therefore, samples of adherent capsules recovered by excision and nonadherent capsules were fixed in pre-cooled 2% paraformaldehyde, buffered with 0.05 m phosphate in saline (pH 7.4), and processed for glycol methacrylate (GMA) embedding [22].…”

Section: Microscopymentioning

confidence: 99%

“…Human trials have been started and showed temporary but pertinent survival of human microencapsulated tissue after allotransplantation of encapsulated parathyroid cells [3] and islets [4]. Also, microencapsulation has been shown to allow for prolonged survival of xenotransplanted islet grafts in both chemically induced and autoimmune diabetic rodents [5], dogs [4], and monkeys [6]. Although this illustrates the principle applicability of the alginateencapsulation technique, a fundamental barrier has to be overcome since graft survival varies considerably from several days to months [7].…”

Section: Introductionmentioning

confidence: 99%

“…Alginates are composed of mannuronic acid (M) and guluronic acid (G) and can be contaminated with inflammatory substances. We found that the biological response against capsules can be reduced by applying alginates with a G-content of 40-45% instead of more than 50% and by introducing alginates with a high purity degree [5,[8][9][10][11]. Also, an inadequate mechanical integrity of the capsules [9,12] can cause immunological reactions in the recipient.…”

Section: Introductionmentioning

confidence: 99%

“…In the present study, we changed the capsule production process by applying modifications which have previously shown to influence the biological response against capsule grafts [5,[8][9][10][11][12]. Empty capsules produced according to our modified procedure were implanted in the peritoneal cavity and retrieved after varying time intervals for evaluation of the biological response against the capsules.…”

Section: Introductionmentioning

confidence: 99%

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Long-term biocompatibility, chemistry, and function of microencapsulated pancreatic islets

et al. 2003

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Section: Alginatesmentioning

confidence: 99%

Section: Microscopymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Long-term biocompatibility, chemistry, and function of microencapsulated pancreatic islets

et al. 2003

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Studies on small (<350 ?m) alginate-poly-L-lysine microcapsules. III. Biocompatibility of smaller versus standard microcapsules

Robitaille¹,

Pariseau²,

Leblond³

et al. 1999

J. Biomed. Mater. Res.

103

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Microencapsulation of islets of Langerhans has been proposed as a means of preventing their immune destruction following transplantation. Microcapsules of diameters <350 microm made with an electrostatic pulse system present many advantages relative to standard microcapsules (700-1500 microm), including smaller total implant volume, better insulin kinetics, better cell oxygenation, and accessibility to new implantation sites. To evaluate their biocompatibility, 200, 1000, 1120, 1340, or 3000 of these smaller microcapsules (<350 microm) or 20 standard microcapsules (1247+/-120 microm) were implanted into rat epididymal fat pads, retrieved after 2 weeks, and evaluated histologically. The average pericapsular reaction increased with the number of small microcapsules implanted (p<0.05; 3000 vs. 200, 3000 vs. 1000, and 1000 vs. 200 microcapsules). At equal volume and alginate content, standard microcapsules caused a more intense fibrosis reaction than smaller microcapsules (p<0.05). In addition, 20 standard microcapsules elicited a stronger pericapsular reaction than 200 and 1000 smaller microcapsules (p<0.05) although the latter represented a 3.4-fold larger total implant surface exposed. We conclude that microcapsules of diameters <350 microm made with an electrostatic pulse system are more biocompatible than standard microcapsules.

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Alginate-poly-L-lysine microcapsule biocompatibility: A novel RT-PCR method for cytokine gene expression analysis in pericapsular infiltrates

Robitaille

Leblond

Henley

et al. 1999

J. Biomed. Mater. Res.

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Transplantation of microencapsulated islets of Langerhans is impaired by a pericapsular host reaction that eventually induces graft failure. We are studying the role of cytokines in the pathogenesis of this reaction, using the model of alginate-polylysine microcapsule implantation in rat epididymal fat pads. The objectives were: (1) to develop a method to measure, by semiquantitative PCR, TGF-beta1 gene expression in fat pad pericapsular infiltrates, and (2) to use this method to evaluate TGF-beta1 gene expression 14 days after microcapsule implantation. TGF-beta1 mRNA level was significantly higher in pericapsular infiltrate cells than in nonimplanted tissue cells and saline-injected tissue cells (p < 0.0001 and p < 0.01, respectively). There was no significant difference between the TGF-beta1 mRNA levels of the two types of controls (p = 0.0945). These results suggest that TGF-beta1 plays a role in the pathogenesis of the pericapsular reaction. The method developed can be used to study the role of other fibrogenic cytokines potentially involved. This will shed light on the mechanisms underlying the pericapsular reaction and will serve as a basis for the development of strategies to control this reaction.

show abstract

The capsular overgrowth on microencapsulated pancreatic islet grafts in streptozotocin and autoimmune diabetic rats

Cited by 43 publications

References 28 publications

Long-term biocompatibility, chemistry, and function of microencapsulated pancreatic islets

Long-term biocompatibility, chemistry, and function of microencapsulated pancreatic islets

Studies on small (<350 ?m) alginate-poly-L-lysine microcapsules. III. Biocompatibility of smaller versus standard microcapsules

Alginate-poly-L-lysine microcapsule biocompatibility: A novel RT-PCR method for cytokine gene expression analysis in pericapsular infiltrates

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