In vitro exposure of pig neonatal isletlike cell clusters to human blood

Background Pig islet grafts have been successful in treating diabetes in animal models. One remaining question is whether neonatal pig isletlike cell clusters (NICC) are resistant to the early loss of islets from the instant blood‐mediated inflammatory reaction (IBMIR). Methods Neonatal isletlike ce...

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Published inXenotransplantation (Københaven) Vol. 22; no. 4; pp. 317 - 324
Main Authors Nagaraju, Santosh, Bertera, Suzanne, Tanaka, Takayuki, Hara, Hidetaka, Rayat, Gina R., Wijkstrom, Martin, Ayares, David, Trucco, Massimo, Cooper, David K. C., Bottino, Rita
Format Journal Article
LanguageEnglish
Published Denmark Blackwell Publishing Ltd 01.07.2015
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ISSN0908-665X
1399-3089
1399-3089
DOI10.1111/xen.12178

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Abstract Background Pig islet grafts have been successful in treating diabetes in animal models. One remaining question is whether neonatal pig isletlike cell clusters (NICC) are resistant to the early loss of islets from the instant blood‐mediated inflammatory reaction (IBMIR). Methods Neonatal isletlike cell clusters were harvested from three groups of piglets—(i) wild‐type (genetically unmodified), (ii) α1,3‐galactosyltransferase gene‐knockout (GTKO)/CD46, and (iii) GTKO/CD46/CD39. NICC samples were mixed with human blood in vitro, and the following measurements were made—antibody binding; complement activation; speed of islet‐induced coagulation; C‐peptide; glutamic acid decarboxylase (GAD65) release; viability. Results Time to coagulation and viability were both reduced in all groups compared to freshly drawn non‐anticoagulated human blood and autologous combinations, respectively. Antibody binding to the NICC occurred in all groups. Conclusions Neonatal isletlike cell clusters were subject to humoral injury with no difference associated to their genetic characteristics.
AbstractList Pig islet grafts have been successful in treating diabetes in animal models. One remaining question is whether neonatal pig isletlike cell clusters (NICC) are resistant to the early loss of islets from the instant blood-mediated inflammatory reaction (IBMIR). Neonatal isletlike cell clusters were harvested from three groups of piglets-(i) wild-type (genetically unmodified), (ii) α1,3-galactosyltransferase gene-knockout (GTKO)/CD46, and (iii) GTKO/CD46/CD39. NICC samples were mixed with human blood in vitro, and the following measurements were made-antibody binding; complement activation; speed of islet-induced coagulation; C-peptide; glutamic acid decarboxylase (GAD65) release; viability. Time to coagulation and viability were both reduced in all groups compared to freshly drawn non-anticoagulated human blood and autologous combinations, respectively. Antibody binding to the NICC occurred in all groups. Neonatal isletlike cell clusters were subject to humoral injury with no difference associated to their genetic characteristics.
Pig islet grafts have been successful in treating diabetes in animal models. One remaining question is whether neonatal pig isletlike cell clusters (NICC) are resistant to the early loss of islets from the instant blood-mediated inflammatory reaction (IBMIR).BACKGROUNDPig islet grafts have been successful in treating diabetes in animal models. One remaining question is whether neonatal pig isletlike cell clusters (NICC) are resistant to the early loss of islets from the instant blood-mediated inflammatory reaction (IBMIR).Neonatal isletlike cell clusters were harvested from three groups of piglets-(i) wild-type (genetically unmodified), (ii) α1,3-galactosyltransferase gene-knockout (GTKO)/CD46, and (iii) GTKO/CD46/CD39. NICC samples were mixed with human blood in vitro, and the following measurements were made-antibody binding; complement activation; speed of islet-induced coagulation; C-peptide; glutamic acid decarboxylase (GAD65) release; viability.METHODSNeonatal isletlike cell clusters were harvested from three groups of piglets-(i) wild-type (genetically unmodified), (ii) α1,3-galactosyltransferase gene-knockout (GTKO)/CD46, and (iii) GTKO/CD46/CD39. NICC samples were mixed with human blood in vitro, and the following measurements were made-antibody binding; complement activation; speed of islet-induced coagulation; C-peptide; glutamic acid decarboxylase (GAD65) release; viability.Time to coagulation and viability were both reduced in all groups compared to freshly drawn non-anticoagulated human blood and autologous combinations, respectively. Antibody binding to the NICC occurred in all groups.RESULTSTime to coagulation and viability were both reduced in all groups compared to freshly drawn non-anticoagulated human blood and autologous combinations, respectively. Antibody binding to the NICC occurred in all groups.Neonatal isletlike cell clusters were subject to humoral injury with no difference associated to their genetic characteristics.CONCLUSIONSNeonatal isletlike cell clusters were subject to humoral injury with no difference associated to their genetic characteristics.
Background Pig islet grafts have been successful in treating diabetes in animal models. One remaining question is whether neonatal pig isletlike cell clusters (NICC) are resistant to the early loss of islets from the instant blood‐mediated inflammatory reaction (IBMIR). Methods Neonatal isletlike cell clusters were harvested from three groups of piglets—(i) wild‐type (genetically unmodified), (ii) α1,3‐galactosyltransferase gene‐knockout (GTKO)/CD46, and (iii) GTKO/CD46/CD39. NICC samples were mixed with human blood in vitro, and the following measurements were made—antibody binding; complement activation; speed of islet‐induced coagulation; C‐peptide; glutamic acid decarboxylase (GAD65) release; viability. Results Time to coagulation and viability were both reduced in all groups compared to freshly drawn non‐anticoagulated human blood and autologous combinations, respectively. Antibody binding to the NICC occurred in all groups. Conclusions Neonatal isletlike cell clusters were subject to humoral injury with no difference associated to their genetic characteristics.
Author Ayares, David
Hara, Hidetaka
Trucco, Massimo
Bertera, Suzanne
Rayat, Gina R.
Cooper, David K. C.
Bottino, Rita
Tanaka, Takayuki
Wijkstrom, Martin
Nagaraju, Santosh
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Keywords pigs
genetically engineered
islets
neonatal
instant blood-mediated inflammatory reaction
diabetes mellitus
xenotransplantation
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2012; 61
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Snippet Background Pig islet grafts have been successful in treating diabetes in animal models. One remaining question is whether neonatal pig isletlike cell clusters...
Pig islet grafts have been successful in treating diabetes in animal models. One remaining question is whether neonatal pig isletlike cell clusters (NICC) are...
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SubjectTerms Animals
Animals, Genetically Modified
Animals, Newborn
Antigens, CD - genetics
Antigens, CD - immunology
Apyrase - genetics
Apyrase - immunology
Blood - immunology
Blood Coagulation
Complement Activation
diabetes mellitus
Diabetes Mellitus - therapy
Galactosyltransferases - deficiency
Galactosyltransferases - genetics
Galactosyltransferases - immunology
Gene Knockout Techniques
genetically engineered
Humans
In Vitro Techniques
instant blood-mediated inflammatory reaction
islets
Islets of Langerhans Transplantation - adverse effects
Islets of Langerhans Transplantation - immunology
Islets of Langerhans Transplantation - pathology
Membrane Cofactor Protein - genetics
Membrane Cofactor Protein - immunology
neonatal
pigs
Recombinant Proteins - genetics
Recombinant Proteins - immunology
Sus scrofa
Transplantation, Heterologous - adverse effects
Transplantation, Heterologous - methods
xenotransplantation
Title In vitro exposure of pig neonatal isletlike cell clusters to human blood
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https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fxen.12178
https://www.ncbi.nlm.nih.gov/pubmed/26179209
https://www.proquest.com/docview/1700105371
Volume 22
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