Use of genetically-engineered pig donors in islet transplantation

Table 1 Genetically-engineered pig islets to diabetic NHP models

GE manipulation	Pig age	Survival (d)	Immunosuppression	Ref.
GTKO	Neonatal	249	Anti-CD154 + anti-LFA1 + CTLA-4-Ig + MMF	[15]
CD46	Adult	396	Anti-CD154 + ATG + MMF	[12]
GTKO/CD46/TFPI/CTLA4-Ig	Adult	365	Anti-CD154 + ATG + MMF	[16]
GTKO/CD55/CD59/HT	Neonatal	30	ATG + MMF + Tacrolimus	[46]

GE: Genetically-engineered; GTKO: Alpha1,3-galactosyl transferase-gene knockout; MMF: Mycophenolate mofetil; TFPI: Tissue factor pathway inhibitor; HT: H-transferase; ATG: Antithymocyte globulin.

Table 2 Several genetic manipulations of pigs currently available with potential use for clinical islet transplantation

GE manipulation	Target	Expression	Ref.
GTKO	Humoral response	Ubiquitous	[15,16,46]
NeuGcKO	Humoral response	Ubiquitous
B4GalNT2KO	Humoral response	Ubiquitous
HumanCD46	Complement regulation	Ubiquitous	[12,16]
HumanCD55	Complement regulation	Ubiquitous	[46]
HumanCD59	Complement regulation	Ubiquitous	[46]
HumanTFPI	Anticoagulation	Beta cells	[16]
HumanCD39	Anticoagulation	Beta cells
Human thrombomodulin	Anticoagulation
Human A20 (tumor necrosis factor-alpha-induced protein 3)	Anticoagulation/anti-inflammatory/anti-apoptotic gene expression
Human heme oxygenase-1	Anticoagulation/anti-inflammatory/anti-apoptotic gene expression
Human signal regulatory protein α	Anticoagulation/anti-inflammatory/anti-apoptotic gene expression
CTLA4-Ig (CD152)	Cellular response	Beta cells	[16]
HLA-E/human b2-microglobulin	Cellular response
LEA29Y	Cellular response
PERV siRNA	PERV activation

GE: Genetically-engineered; GTKO: Alpha1,3-galactosyl transferase-gene knockout; TFPI: Tissue factor pathway inhibitor; PERV: Porcine endogenous retroviruse.