Table 8.

Xenogeneic rejection mechanism of orthotopic corneal xenotransplantation in pig-to-small or medium sized animal model.

Recipient type	References	Type (PKP/lamellar)	Donor pig breed	Recipient	Donor size (mm)	N	MST (Days)	Histology of the rejected grafts/plasma
Rat	Lee et al. (2007)	PLK	Landrace	rat	6.0	21	8.8	•αGal in corneal epithelial, stromal & endothelial cells
	Lee et al. (2008)	PLK	Domestic	Sprague-Dawley rat	6.0	21	9.3	•CD8+ cells > CD4+ cells •PMN, neutrophils & monocytes
				Sprague-Dawley rat (+ISa)		70	9.1
	Oh et al. (2009b)	PLK	SNU miniature	Sprague–Dawley rat	5.0	5	9.7	•Neutrophils & macrophages ↑↑ •CD8+ cells > CD4+ cells •Rare NK cell
				Sprague–Dawley rat (+allogeneic rat MSC)		5	10.5
	Lee et al. (2010)	IST	Domestic	Sprague–Dawley rat (+topical steroid)	2.0	40	14.0	•CD45RO+ T cells & CD68+ cells
Mouse	Oh et al. (2009a)	PLK	SNU miniature	BALB/c	3.0	10	9.0
				C57BL/6		12	9.0	•PMN, neutrophil, eosinophil ↑↑ at D4 •Lymphocyte, monocyte, macrophage↑↑ at D13 •Macrophages » CD4+ T cells •Rare CD8+ T cell/NK cell
				Athymic Nude		10	16.0c	•Macrophages & CD4+ T cells ↓
				SCID		12	16.4c	•Macrophages & CD4+ T cells ↓↓
				NOG		5	16.9	•Macrophages ↓↓ •No CD4+ T/CD8+ T/NK cell
	Oh et al. (2010)	PLK	Domestic	C57BL/6	3.0	18	9.4	•Macrophages & CD4+ T cells ↑↑ •Deposition of Ig M & Ig G ↑ •Rare CD8+ T cell/NK cell
				SCID		18	16.4	•Macrophages ↓ •No CD4+ T/CD8+ T cell
				C57BL/6 (+CVF)		18	15.5d	•Macrophages & CD4+ T cells ↓ •Deposition of Ig M & Ig G ↓ •Rare CD8+ T cell/NK cell
				SCID (+CVF)		18	20.5d	•Macrophages ↓↓ •No CD4+ T/CD8+ T cell
	Choi et al. (2011a)	PLK	SNU miniature	C57BL/6	2.5	4	8	•Less IgG deposit
				GT-KO (H-2b)		4	9	•CD4+ cells & macrophages ↑ •Rare CD8+ cells/NK cells •Deposition of Ig M & Ig G ↑ •Plasma anti-αGal Ig G ↑
medium	Oh et al. (2008)	ALK	SNU miniature	rabbit	6.0	10	19-28b	•Inflammatory cells ↑↑↑ (258 ± 10/400 HPF)
	Oh et al. (2009c)	ALK	SNU miniature	rabbit	7.0	8	29.1e	•Monocytes/lymphocytes »> eosinophil > PMN (258 ± 60/400 HPF)
		PKP			7.5	8	16.8	•Eosinophil»>monocytes > PMN (209 ± 71/400 HPF)
	Oh et al. (2009d)	ALK	SNU miniature	rabbit	8.0	7	28	•CD3+ lymphocytes ↑↑↑ at 1 M

Abbreviations: Ab: antibody, αGal: Galα1-3Galβ1-4GlcNAc-R, ALK: anterior lamellar keratoplasty, CD: cluster of differentiation, CVF: cobra venom factor, D: days, HPF: high power field, GT-KO: α1,3-galactosyltransferase gene-knockout, IS: Immunosuppressant, IST: intrastromal transplantation, M: months, MSC: mesenchymal stem cells, MST: median survival time, N: number of animals experimented, NK: natural killer, NOG: NOD/SCID/γc^null, PLK: posterior lamellar keratoplasty, PMN: polymorphonuclear, SCID: severe combined immunodeficiency, SNU: Seoul National University, WT: wild-type.

^aVariable combinations of Immunosuppressant applied based on as follows; systemic cyclosporin A 1.25–10.0 mg/kg, dexamethasone 1.0–2.0 mg/kg, Mycophenolate mofetil 1.25 mg/kg.

^bMST is not available.

^cStatistically significant longer survival compared with that of control.

^dStatistically significant longer survival compared with that of control (B6 vs B6+CVF; SCID vs SCID + CVF).

^eStatistically significant longer survival of ALK compared with that of PKP.