title: Effect of alginate encapsulation on the cellular transcriptome of human islets.
abstract: Encapsulation of human islets may prevent their immune rejection when transplanted into diabetic recipients. To assist in understanding why clinical outcomes with encapsulated islets were not ideal, we examined the effect of encapsulation on their global gene (mRNA) and selected miRNAs (non-coding (nc)RNA) expression. For functional studies, encapsulated islets were transplanted into peritoneal cavity of diabetic NOD-SCID mice. Genomics analysis and transplantation studies demonstrate that islet origin and isolation centres are a major source of variation in islet quality. In contrast, tissue culture and the encapsulation process had only a minimal effect, and did not affect islet viability. Microarray analysis showed that as few as 29 genes were up-regulated and 2 genes down-regulated (cut-off threshold 0.1) by encapsulation. Ingenuity analysis showed that up-regulated genes were involved mostly in inflammation, especially chemotaxis, and vascularisation. However, protein expression of these factors was not altered by encapsulation, raising doubts about the biosignificance of the gene changes. Encapsulation had no effect on levels of islet miRNAs. In vivo studies indicate differences among the centres in the quality of the islets isolated. We conclude that microencapsulation of human islets with barium alginate has little effect on their transcriptome.
authors: Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, Australia.
authors: Vijayaganapathy
authors: V
authors: Vaithilingam
authors: Nayeem
authors: N
authors: Quayum
authors: Mugdha V
authors: MV
authors: Joglekar
authors: Jan
authors: J
authors: Jensen
authors: Anandwardhan A
authors: AA
authors: Hardikar
authors: Jose
authors: J
authors: Oberholzer
authors: Gilles J
authors: GJ
authors: Guillemin
authors: Bernard E
authors: BE
authors: Tuch
mesh_terms: D000464:Alginates / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D015536:Down-Regulation / Q000187:drug effects; D020869:Gene Expression Profiling; D020723:Glucuronic Acid / Q000737:chemistry / Q000494:pharmacology; D006603:Hexuronic Acids / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000464:Alginates; D017931:DNA Primers; D006603:Hexuronic Acids; D007328:Insulin; D020723:Glucuronic Acid