Table 2.

Major anti-oxidative and anti-inflammatory chemicals used in pancreas preservation, islet isolation, and islet culture.

Chemicals	Benefits	Limitation	References
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]