Table 11.

Preclinical efficacies of decellularized porcine corneal xenotransplantation in rabbit or non-human primate studies^a.

References	Type	Decellularization method	Donor	Recipient	Graft size (mm)/Thickness (㎛)	Survival days of each recipient	Immunosuppression	Histology
Zhang et al. (2007)	ALK	Dispase/Triton X-100/Trypsin/DNase/RNase/Freeze-thaw	Domestic WT	Rabbit	4.0/NA	>224 (n = 20)b	None	•Few inflammatory cells •Partially degraded cornea
Amano et al. (2008)	ALK	N2	Domestic WT	Rabbit	5.0/100-200	>180 (n = 3)	None	•Few keratocytes infiltration
Lin et al. (2008)	ALK	Distilled water/Trypsin/freeze-thaw/NaOH/DNase/RNase	Domestic WT	Rabbit	6.5/200	Transparency maintained in 83% (10/12) of grafts	None	•Similar to the normal cornea
Xu et al. (2008)	ALK	Dispase/Triton X-100/Trypsin/EDTA/DNase/RNase	Domestic WT	Rabbit	4.0/NA	>28 (n = 15)b	None	•Similar normal rabbit stromal histological appearance
Oh et al. (2009d)	ALK	Freezing	SNU miniature WT	Rabbit	8.0/250	20, 20, 20, 24, 24, 28, 28	None	•CD3+ cells in rejected graft
		Freeze–thaw				43, 43, 47, 47, 60, 60, 60
		Hypertonic NaCl/Trypsin/EDTA				>30c, >60c, >180, >180, >180, >180, >180
		Trypsin/EDTA/Glycerol				16, 18, 18, 18, 20, 20, 20
		Trypsin/Dispase/SDS				All 0 (n = 7)
		NaOH/DNase/RNase				All 0 (n = 7)
Wu et al. (2009)	ALK	PLA2/sodium deoxycholate	Yorkshire WT	Rabbit	6.0/100	>10 (n = 2)c,> 50 (n = 2)c, >84 ± 11 (n = 10)c, >360 (n = 10)	Topical steroid	•No inflammatory cells and graft degradation
Sasaki et al. (2009)	IST	Hydrostatic pressure/DNase	Domestic WT	Rabbit	2.0/160	>56 (n = 11)	None	•Minimal inflammation around the donor tissue
Hashimoto et al. (2010)	IST	Hydrostatic pressure/DNase	Domestic WT	Rabbit	2.0/160	>360 (n = 6)	None	•No macrophage/monocytes
Pang et al. (2010)	IST	SDS	Domestic WT	Rabbit	6.0/150	>14 (n = 2)c, >28 (n = 2)c, >84 (n = 2)c, >168 (n = 4)	Subconjunctival steroid	•Well integrated within the host corneas, with some cell infiltrations
Lee et al. (2011)	ALK + substance-P	DNase/RNase/Distilled water/Freeze-thaw/Glycerol/Lyophilization	Domestic WT	Rabbit	4.0/300	>56 (n = 5)b	None	•Stromal cell infiltration
Zhou et al. (2011)	IST	SDS	Yorkshire WT	Rabbit	10.0/150	>330 (n = 30)b	Subconjunctival steroid	•Collagen diameters remained unchanged
Li et al. (2011)	ALK	Calcium chloride	WZS miniature WT	NHP	7.0/AHL	>180 (n = 5), >180 (n = 5)	None/Subconjunctival steroid	•Some inflammatory cells at graft junction
Choi et al. (2011b)	DALK	Hypertonic NaCl/Trypsin/EDTA	SNU miniature WT	NHP	7.5/312.5–375	>391, >265, >208, >195, 28	Topical, subconjunctival, and systemic steroid	•Mainly CD8+ T cells and macrophages in the rejected graft
Du and Wu (2011)	IST	SDS	Domestic WT	Rabbit	5.0/150	>14 (n = 4)c, >28 (n = 4)c, >56 (n = 4)c, >84 (n = 4)c, >168 (n = 4)	None	•No inflammation, recipient keratocytes migrated from 12 weeks after transplantation
Yoeruek et al. (2012b)	IST	EDTA/SDS/DNase/RNase	Domestic WT	Rabbit	3.0/100	>180 (n = 10)	Topical steroid	•Dense cellular infiltration
Luo et al. (2013)	ALK	Ultrapure water/Hypertonic saline/Triton X-100/Glycerol	Domestic WT	Rabbit (alkali burn)	NA/300	<15 (n = 6)	Topical steroid	•Immune cells in the corneal stroma •Irregular fibril distribution
Hashimoto et al. (2015)	DALK	Hydrostatic pressure/DNase	Domestic WT	Rabbit	6.0/300	>180 (n = 6)	Topical steroid	•No inflammatory cells
Shao et al. (2015)	IST, ALK	Human serum/electrophoresis	NA	Rabbit	6.0/300	>60 (n = 13)b	None	•Very few cell infiltrations
Hashimoto et al. (2016)	ALK	Hydrostatic pressure/DNase	Domestic WT	Rabbit	4.0/160	>180 (n = 6)	None	•No inflammatory cells
Li et al. (2017b)	ALK	Deionized water/Freeze–thaw/DNase/RNase/Ultrasound	Domestic WT	Rabbit	6.5/450	>84 (n = 3)	None	•Almost similar to those of a normal cornea
	ALK (cross-linked)	Glycerol, crosslinked with NHS and EDC		Rabbit (ulcer)	7.75/250	72.3% (8/11) >168	Topical tacrolimus	•No inflammatory cells •Stromal cell growth into the superficial stroma
Huang et al. (2017)	ALK	Ultrapure water/NaCl/SCCO2/Glycerol	Domestic WT	Rabbit	6.0/NA	>60 (n = 3)c, >180 (n = 3)	Topical steroid	•No macrophages, neutrophils
Zheng et al. (2018)	IST	SDS	Domestic WT	Rabbit	7.0/126	>168 (n = 8)	Topical steroid	•Intact corneal structure, no infiltrating cells

Abbreviations: AHL: anterior half lamella, ALK: anterior lamellar keratoplasty, CD: cluster of differentiation, DALK: deep anterior lamellar keratoplasty, EDC: 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, EDTA: ethylenediaminetetraacetic acid, IST: intrastromal transplantation, NA: not available, NHS: N-Hydroxysulfosuccinimide, SCCO₂: supercritical carbon dioxide, SDS: sodium dodecyl sulfate, SNU: Seoul National University, WT: wild-type, WZS: Wuzhishan.

^aStudies using tissue engineered decellularized porcine cornea are not included in this table.

^bSome recipients were sacrificed at specific time points for histologic examinations.

^cSacrificed for histology.