Efficacy of Pig-to-Rhesus Lamellar Corneal Xenotransplantation

被引:67
作者
Choi, Hyuk Jin [1 ,2 ,4 ]
Kim, Mee Kum [1 ,4 ]
Lee, Hyun Ju [4 ]
Ko, Jung Hwa [4 ]
Jeong, So Hee [4 ]
Lee, Jae-Il [3 ]
Oh, Byoung-Chol [3 ]
Kang, Hee Jung [5 ]
Wee, Won Ryang [1 ,4 ]
机构
[1] Seoul Natl Univ, Coll Med, Dept Ophthalmol, Seoul 110744, South Korea
[2] Seoul Natl Univ Hosp, Healthcare Syst Gangnam Ctr, Dept Ophthalmol, Seoul 110744, South Korea
[3] Seoul Natl Univ Hosp, Xenotransplantat Res Ctr, Seoul 110744, South Korea
[4] Seoul Natl Univ Hosp, Biomed Res Inst, Seoul Artificial Eye Ctr, Lab Corneal Regenerat Med & Ocular Immunol, Seoul 110744, South Korea
[5] Hallym Univ, Coll Med, Dept Lab Med, Anyang, South Korea
关键词
ASSOCIATION CONSENSUS STATEMENT; UNDERTAKING CLINICAL-TRIALS; TISSUE-ENGINEERED CORNEA; CELL-MEDIATED REJECTION; PORCINE ISLET PRODUCTS; HYPERACUTE REJECTION; RABBIT; DONORS; MATRIX; TRANSPLANTATION;
D O I
10.1167/iovs.11-7273
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
PURPOSE. To solve the shortage of donor corneas, a decellularizing method based on hypertonic saline treatment was introduced, and a favorable outcome was observed in pig-to-rabbit lamellar corneal transplantation. This study was an investigation of the efficacy of pig-to-nonhuman primate lamellar corneal transplantation, using both decellularized and fresh porcine corneas to assess feasibility as a substitute for human corneas. METHODS. Nine Chinese rhesus macaques underwent lamellar corneal transplantation using both decellularized (n = 5) and fresh (n = 4) porcine corneas. Clinically acceptable graft size (7.5 mm in diameter) and minimal immunosuppression based on topical and systemic corticosteroids were applied. Rejection signs, histology of porcine grafts, and serial changes in recipients' blood profile, including memory T-cell subset, anti-alpha-Gal and donor pig-specific antibodies, and complement were evaluated. Changes in aqueous complement concentration were also assessed at 4 weeks after transplantation. RESULTS. Of the decellularized porcine lamellar grafts, 80% remained transparent for more than 6 months, whereas half of the fresh porcine lamellar grafts developed chronic rejection. Rejected grafts showed extensive cellular infiltration, predominantly CD8(+) T lymphocytes and macrophages. Immunologic profiles of the recipients with rejected grafts showed a significant increase in the concentration of aqueous complement, an enhancement of memory T cells, and an abrupt increase in donor pig-specific antibodies. CONCLUSIONS. The findings suggested that decellularized porcine cornea could be a promising substitute for human corneal allograft. Fresh porcine cornea may be a feasible option for a substitute if combined with more potent immunosuppression or if obtained from transgenic pigs with complement-regulatory proteins. (Invest Ophthalmol Vis Sci. 2011; 52: 6643-6650) DOI: 10.1167/iovs.11-7273
引用
收藏
页码:6643 / 6650
页数:8
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