The Fate of Allogeneic Pancreatic Islets following Intraportal Transplantation: Challenges and Solutions

Table 1

Selected treatment options for islet graft and islet transplant recipient on targets associated with IBMIR.

Donor (in vitro pretreatment)		Recipient (in vivo treatment)
Agent	Mechanism	Agent	Mechanism
Coagulation
Anti-TF mAb	Anti-TF	Anti-TF mAb	Anti-TF
Nicotinamide	Downregulation of TF expression on isolated islets	Heparin	Anticoagulation
Surface engineering of islets; (i) Heparin coating; (ii) PEG coating; (iii) Composite islet-endothelial cell graft	Covering of islets to prevent direct exposure to blood	LMW-DS	Anticoagulation
		Melagatran	Anticoagulation via thrombin inhibition
		Nacystelyn	Anticoagulation, anti-inflammatory, & antioxidant effects
		Activated protein C	Anticoagulation, fribrinolysis, NF-κB inhibition
		Thrombomodulin	Anticoagulation via thrombin inhibition
		Glycoprotein IIb/IIIa inhibitors	Inhibiting fibrinogen binding to the receptors to prevent platelet activation and aggregates
Complement
α-Antitrypsin	Complement inhibition	LMW-DS	Complement inhibition
		Compstatin	Complement inhibition
		Cobra venom factor	Depleting the complements
		sCR1 (TP10)	Negative regulator of the complement cascade that inhibits both the classic and alternative pathways
		C5a inhibitory peptide (C5aIP)	Blocks the deleterious effects of C5a to reduce complement activation, the chemotactic effect, and inflammatory reactions
Proinflammatory mediators
α-Antitrypsin	Blockade of PIC production	α-Antitrypsin	Blockade of PIC production
Antioxidant	Scavenging of reactive oxygen species produced the isolation process	15-DSG	Blockade of PIC production via NF-κB inhibition
Statins	Protection against ischemia-reperfusion injury; Inhibition of proapoptotic pathways	Anti-TNF-α mAb	Binding to TNF-α prevents the stimulation of its receptor
Heme oxygenase-1 induction	Anti-inflammatory effects via p38 MAPK-dependent pathway	IL-1 receptor antagonist	Prevention of IL-1β from binding to the IL-1 receptor
A-20 induction	Anti-inflammatory effects via NF-κB inhibition potent antiapoptotic gene	Reparixin	Binding to CXCR1/2 to block the CXCL8/IL-8 axis
Active vitamin D	Anti-inflammatory effects by induction of protective gene expression	zVAD-FMK	Pan-caspase inhibitor that suppresses cell apoptosis
Withaferin A	Anti-inflammatory effects via NF-κB inhibition	IDN-6556	Pan-caspase inhibitor that suppresses cell apoptosis
JNK inhibitor	Anti-inflammatory effects by reduction of PIC production; Antiapoptotic effects via JNK inhibition	JNK inhibitor	Anti-inflammatory effects by reduction of PIC production; Antiapoptotic effects via JNK inhibition
		GLP-1 R agonist; (i) Exenatide (short half-life); (ii) Liraglutide (long half-life)	Reducing apoptosis due to oxidative stress & enhancing insulin release; Anti-inflammatory & antioxidative properties

IBMIR = instant blood-mediated inflammatory reaction; PIC = proinflammatory cytokines; TF = tissue factor; LMW-DS = low-molecular-weight dextran sulfate; TNF-α = tumor necrosis factor-α; sCR1 = soluble complement receptor type 1; 15-DSG = 15-deoxyspergualin; GLP-1R = glucagon-like peptide-1 receptor; IL = interleukin; JNK = c-Jun N-terminal kinase; MAPK = mitogen-activated protein kinase; CXCL = CXC chemokine ligand; CXCR = CXC chemokine receptor.