Jagdale Abhijit, Iwase Hayato, Klein Edwin C, Cooper David Kc
Xenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
Department of Laboratory Animal Resources, University of Pittsburgh, Pittsburgh, Pennsylvania.
Comp Med. 2019 Apr 1;69(2):86-94. doi: 10.30802/AALAS-CM-18-000093. Epub 2019 Mar 25.
As clinical pig organ xenotransplantation draws closer, more attention is being paid to diseases that affect pigs and those that provide a potential risk to human recipients of pig organs. Neoplasia arising from the pig organ graft is one such concern. Various tumors and other neoplastic diseases are well known to show increased incidence in organ allotransplant recipients receiving immunosuppressive therapy. Whether this effect will prove to be the case after xenotransplantation has not yet been established. Malignant tumors in young pigs are rare, with lymphosarcoma, nephroblastoma, and melanoma being the most common. The combination of noninvasive techniques and intraoperative examination of the pig organ likely will readily confirm that a pig organ graft is tumor-free before xenotransplantation. Posttransplantion lymphoproliferative disorder (PTLD) is a concern after allotransplantation, but the incidence after solid organ allotransplantation is low when compared with hematopoietic cell allotransplantation (for example, bone marrow transplantation), unless immunosuppressive therapy is particularly intensive. Organ-source pigs used for clinical xenotransplantation will be bred and housed under designated pathogen-free conditions and will be free of the γ-herpesvirus that is a key factor in the development of PTLD in pigs. Therefore if a recipient of a pig xenograft develops PTLD, it will almost certainly be of recipient origin. The increasing availability of organs from pigs genetically-engineered to protect them from the human immune response likely will diminish the need for intensive immunosuppressive therapy. Considering the low incidence of malignant disease in young pigs, donor-derived malignancy is likely to be rare in patients who receive pig organ grafts. However, if the graft remains viable for many years, the incidence of graft malignancy may increase.
随着临床猪器官异种移植日益临近,人们越来越关注影响猪的疾病以及那些可能给猪器官人类接受者带来潜在风险的疾病。猪器官移植中出现的肿瘤就是这样一个令人担忧的问题。众所周知,各种肿瘤和其他肿瘤性疾病在接受免疫抑制治疗的器官同种异体移植受者中发病率会增加。异种移植后是否也会出现这种情况尚未确定。幼猪中的恶性肿瘤很少见,最常见的是淋巴肉瘤、肾母细胞瘤和黑色素瘤。在异种移植前,结合非侵入性技术和对猪器官的术中检查,很可能会很容易地确认猪器官移植没有肿瘤。移植后淋巴细胞增殖性疾病(PTLD)是同种异体移植后的一个问题,但与造血细胞同种异体移植(例如骨髓移植)相比,实体器官同种异体移植后的发病率较低,除非免疫抑制治疗特别强化。用于临床异种移植的器官源猪将在指定的无特定病原体条件下饲养,并且不会感染γ-疱疹病毒,而γ-疱疹病毒是猪PTLD发生的关键因素。因此,如果猪异种移植受者发生PTLD,几乎可以肯定是受者自身起源的。越来越多的经过基因工程改造以保护其免受人类免疫反应影响的猪器官,可能会减少对强化免疫抑制治疗的需求。考虑到幼猪中恶性疾病的发病率较低,供体来源的恶性肿瘤在接受猪器官移植的患者中可能很少见。然而,如果移植器官存活多年,移植器官恶性肿瘤的发病率可能会增加。