Genetically Engineered Islets and Alternative Sources of Insulin-Producing Cells for Treating Autoimmune Diabetes: Quo Vadis?

Table 1

Transgenic overexpression of regulatory genes in the islets and their effects on islet transplantation.

Promoter	Gene of interest	Animal strain	Diabetic incidence	Effect on islets	Effects on islet transplantation	Reference
Human insulin	IL-4	NOD	Decreased	Protect islets from autoimmune destruction	No significant protective effect	[21]
Rat insulin	TGF-β	NOD	Decreased	Small clusters of micro-islet	N, and no protective effect when use pancreata in an allogeneic transplantation model	[22, 23]
Glucagon	TGF-β	NOD	Decreased	Morphologically normal, no other phenotypes mentioned	N	[24]
Rat insulin	TNF-α	NOD	Decreased	Massive insulitis	N	[25]
Human insulin	SOCS1	B6	B6 is not a diabetes-prone mouse strain	Not mentioned	Expression of SOCS-1 in islets delays allografts rejection (B6 to Balb/c) but cannot circumvent destruction of the islets by the recurrence of the tissue-specific autoimmune process of spontaneous diabetes (B6 to diabetic NOD)	[26]
Human insulin	PD-L1	NOD	Decreased	Protect from autoimmune destruction	No significant protective effect	[27]
Glial fibrillary acidic protein	PD-L1	NOD	Increased	Enhance the severity of insulitis	N	[28]
Rat insulin	PD-L1	B6	Induces T-cell-mediated spontaneous diabetes in B6 mouse	Induce insulitis	Accelerate allograft rejection	[29]
Human insulin	Single chain anti-CTLA-4 Fv	NOD	Decreased	Protect islets from autoimmune destruction	Prolong islet grafts survival in diabetic NOD mice	[30]
Rat insulin	CTLA-4-Ig	B6	B6 is not a diabetes-prone mouse strain	Morphologically normal	N, and transplantation of CTLA4-Ig transgenic pancreata combine with transient systemic CD4 T cell depletion in recipients enhance allograft acceptance	[31]
Human insulin	Thioredoxin	NOD	Decreased	Do not attenuate the development of insulitis	N	[32]
Human insulin	Heme oxygenase 1	NOD	Decreased	Protect islets from autoimmune destruction; Resistant to inflammatory cytokine-induced apoptosis	Prolong islet grafts survival in diabetic NOD mice	[33]
Human insulin	DcR3	NOD	Decreased	Protect islets from autoimmune destruction	Increase the successful rate of implantation and prolong islet grafts survival in diabetic NOD mice	[34]
Human insulin	D6	NOD	Decreased	Protect islets from autoimmune destruction	N	[35]

NOD: Nonobese diabetic mouse, a spontaneous autoimmune diabetes mouse strain; SOCS-1: suppressor of cytokine signaling-1; PD-L1: programmed death 1 ligand 1; CTLA-4: cytotoxic T lymphocyte antigen 4; DcR3: decoy receptor 3; D6: an inflammatory CC chemokine decoy receptor; N: not tested.