Powell Ellis J, Charley Sara, Boettcher Adeline N, Varley Lisa, Brown Justin, Schroyen Martine, Adur Malavika K, Dekkers Susan, Isaacson Dean, Sauer Mary, Cunnick Joan, Ellinwood N Matthew, Ross Jason W, Dekkers Jack Cm, Tuggle Christopher K
1 Department of Animal Science, Iowa State University, USA.
2 Swine Medicine Education Center, Iowa State University, USA.
Lab Anim. 2018 Aug;52(4):402-412. doi: 10.1177/0023677217750691. Epub 2018 Jan 11.
Severe combined immunodeficiency (SCID) is defined by the lack of an adaptive immune system. Mutations causing SCID are found naturally in humans, mice, horses, dogs, and recently in pigs, with the serendipitous discovery of the Iowa State University SCID pigs. As research models, SCID animals are naturally tolerant of xenotransplantation and offer valuable insight into research areas such as regenerative medicine, cancer therapy, as well as immune cell signaling mechanisms. Large-animal biomedical models, particularly pigs, are increasingly essential to advance the efficacy and safety of novel regenerative therapies on human disease. Thus, there is a need to create practical approaches to maintain hygienic severe immunocompromised porcine models for exploratory medical research. Such research often requires stable genetic lines for replication and survival of healthy SCID animals for months post-treatment. A further hurdle in the development of the ISU SCID pig as a biomedical model involved the establishment of facilities and protocols necessary to obtain clean SPF piglets from the conventional pig farm on which they were discovered. A colony of homozygous SCID boars and SPF carrier sows has been created and maintained through selective breeding, bone marrow transplants, innovative husbandry techniques, and the development of biocontainment facilities.
严重联合免疫缺陷(SCID)的定义是缺乏适应性免疫系统。导致SCID的突变在人类、小鼠、马、狗中自然存在,最近在猪中也被发现,爱荷华州立大学的SCID猪就是意外发现的。作为研究模型,SCID动物对异种移植具有天然耐受性,并为再生医学、癌症治疗以及免疫细胞信号传导机制等研究领域提供了有价值的见解。大型动物生物医学模型,尤其是猪,对于提高新型再生疗法对人类疾病的疗效和安全性越来越重要。因此,需要创建实用的方法来维持用于探索性医学研究的卫生严重免疫受损猪模型。此类研究通常需要稳定的遗传品系,以便在治疗后数月内使健康的SCID动物进行繁殖和存活。将爱荷华州立大学的SCID猪开发为生物医学模型的另一个障碍涉及建立必要的设施和方案,以便从发现它们的传统养猪场获得清洁的无特定病原体(SPF)仔猪。通过选择性育种、骨髓移植、创新的饲养技术以及生物安全设施的开发,已经创建并维持了一个纯合SCID公猪和SPF携带母猪的群体。