|
| 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] |
|
