The Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Xenotransplantation. 2010 Mar-Apr;17(2):147-52. doi: 10.1111/j.1399-3089.2010.00576.x.
Allogeneic skin is currently the best alternative to autologous skin as a temporary treatment for severe burns, but it has several drawbacks. As a potential alternative, we have evaluated GalT-KO swine skin, which lacks expression of the Gal epitope, to investigate the effect of eliminating this epitope on survival of pig-to-baboon skin grafts.
Two adult baboons that had fully recovered from previous T cell depletion received simultaneous skin grafts from: (i) GalT-KO swine, (ii) Gal-positive swine, (iii) a third-party baboon, and (iv) self (control skin). Recipients were treated with cyclosporin for 12 days and the survival, gross appearance, and histology of the grafts were compared.
In both baboons, the GalT-KO skin survived longer than either the Gal-positive swine skin or the allogeneic skin. Early rejection of the Gal-positive skin appeared to be mediated by cytotoxic preformed anti-Gal IgM antibodies, while the rejection of GalT-KO skin appeared to result from cellular mechanisms.
GalT-KO skin may have potential clinical benefits as an alternative to allogeneic skin as a temporary treatment for severe skin injuries.
同种异体皮肤目前是自体皮肤的最佳替代品,可作为严重烧伤的临时治疗方法,但存在一些缺点。作为一种潜在的替代方法,我们评估了缺乏 Gal 表位表达的 GalT-KO 猪皮,以研究消除该表位对猪到狒狒皮肤移植物存活的影响。
两只从先前 T 细胞耗竭中完全恢复的成年狒狒同时接受来自以下来源的皮肤移植:(i)GalT-KO 猪,(ii)Gal 阳性猪,(iii)第三方狒狒,和(iv)自身(对照皮肤)。受者接受环孢素治疗 12 天,并比较移植物的存活、大体外观和组织学。
在两只狒狒中,GalT-KO 皮肤的存活时间均长于 Gal 阳性猪皮肤或同种异体皮肤。Gal 阳性皮肤的早期排斥似乎是由细胞毒性预先形成的抗 Gal IgM 抗体介导的,而 GalT-KO 皮肤的排斥似乎是由细胞机制引起的。
GalT-KO 皮肤可能具有潜在的临床益处,可作为严重皮肤损伤的临时治疗方法,替代同种异体皮肤。