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Chemicals | Benefits | Limitation | References |
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AEOL10150 AEOL10113 | (i) Antioxidative (SOS mimics) used in both isolation stage and culture (ii) Reduction of NF-κB binding of DNA (iii) ↓IL-6,8; ↓MCP-1 (iv) Inhibition of the release of cytokines and chemokines and PARP activation (v) Protection of islets from oxidative stress | (i) No in vivo islet graft function available (ii) Has not been demonstrated by other groups | [58, 59] |
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Glutamine | (i) Benefits in both animal and human models during islet isolation (ii) Increasing of GSH levels (iii) Reduction of malondialdehyde and apoptotic cells (iv) Improvement of in vivo islet graft function | (i) Needs to be demonstrated by large-scale or multicenter studies (ii) Short-term effect due to instability and short half-life of glutamine (iii) Relationship with inflammatory cascade needs to be tested | [60–66] |
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SS-31 | (i) Water-soluble antioxidative peptide with high islet penetration (ii) Specific mitochondrial targeting (iii) Preservation of mitochondrial polarization and reduced apoptosis (iv) Improvement of islet in vivo function | (i) Needs to be demonstrated by large-scale or multicenter studies (ii) Only tested in animal model | [67, 68] |
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NMMA Aminoguanidine N-acetyl cysteine Glutathione peroxidase | (i) Blockage of NO production via inhibition of iNOS in rodent and human islets (ii) Enhancement of islet antioxidant capability | (i) Only demonstrated in vitro (ii) The benefits for islet transplant need to be shown | [69–75] |
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Vitamins (D3, E, Riboflavin, C) | (i) Increased insulin secretion (ii) Higher islet viability (iii) Increased insulin gene expression (iv) Decreased lipid peroxidation | (i) Application in human islet isolation is limited (ii) No documented benefits on human islet receipts | [76] |
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Anakinra | (i) IL-1R antagonist via competitive inhibition (ii) ↓TNF-α; ↓IL-1β; ↓IFN-γ (iii) FDA approved as anti-inflammatory agent | (i) Not demonstrated in human islet isolation and transplant | [77–81] |
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Pan-caspase (ZVAD-FMK) and selective caspase inhibitor (zVD-FMK) | (i) Reduced islet loss during culture (ii) Improve islet graft function (iii) Reduced islet cell apoptosis | (i) No demonstrated benefits in human islet receipts | [82–84] |
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Prolactin | (i) Increased β-cell proliferation (ii) Increased insulin secretion (iii) Cytoprotection (iv) Improved islet engraftment (v) Increased islet revascularization (vi) Increased BCL2/BAX ratio (vii) Inhibition of caspase 8, 9 and 3 | (i) Less understanding of mechanism (ii) Needs to be demonstrated by large-scale or multicenter studies | [85–88] |
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JNK inhibitor | (i) Increased islet yield (ii) Improved islet viability (iii) Improved in vivo graft function | (i) Limited information on human patients (ii) Large-scale study need to confirm | [89–93] |
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Pefabloc | (i) Efficient inhibition of serine protease activity (ii) Has been applied in all phases of isolation (iii) No interference with collagenase activity | (i) Controversial results on islet yield (ii) Inhibited insulin secretion in vitro | [94–98] |
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