Table 1.

Summary of immune protection studies for stem cell-derived islets or primary islets.

Strategy	Method		Target Cell Type	Side Effect(s)	Predicted Efficacy (Allo or Auto)	In vivo transplantation	Reference
Gene targeting/Engineering	PD-L1 overexpression		β-cells	Unknown	Allogeneic Autoimmune	Yes (Rodents)	(83) (187)
Immune suppressants	Induction immunosuppression (e.g. antithymocyte globulin, basiliximab, etanercept) with maintenance agents (e.g. sirolimus, tacrolimus)		T-cells, NKT cells, etc.	Induction of malignancies, greater risk of infection, autoreactivity	Allogeneic	Yes (Rodents)	(30) (31) (107–110)
					Autoimmune	Yes (Human)
MHC matching	Generation of HLA-homozygous hiPSC lines		hiPSCs, hESCs	Unknown	Allogeneic	Yes (Rodents)	(172–174)
Macro encapsulation	Protection of grafts from host immune cell infiltration via a physical barrier	Theracyte device	β-cells	Fibrotic responses, Prevention of vascularization in the graft, Hypoxia	Allogeneic	Yes (Rodents)	(112–116)
		βAir device		Fibrotic responses, Prevention of vascularization in the graft	Autoimmune	Yes (Human)	(117, 118)
		Nanofiber		Prevention of vascularization in the graft, Hypoxia			(119, 140, 141)
Micro encapsulation	Encapsulation of grafts in biomaterials with low immunogenic profiles	Alginate	β-cells	Unknown	Allogeneic	Yes (Rodents)	(120, 121, 123–128, 130, 132–139)
		SA-PDL-1		Unknown	Autoimmune		(188, 189)
Preconditioning	Exposure of grafts to ischemia, hypoxia, or co-culturing to enhance immune tolerance and graft survival		β-cells or co-cultured cells (e.g. mesenchymal stem cells, primary hepatocytes)	Unknown	Allogeneic	Yes (Rodents)	(142, 143, 146–151)
Transcriptional memory	Multi-pulse IFNγ stimulation to induce transcriptional memory to induce PD-L1 expression and De novo cytokine tolerance		β-cells	Unknown	Allogeneic	Yes (Rodents)	(87)
					Autoimmune