Center for Transplantation Science (CTS), Massachusetts General Hospital, Boston, Massachusetts, USA.
XenoTherapeutics, Inc., Boston, Massachusetts, USA.
J Burn Care Res. 2020 Feb 19;41(2):306-316. doi: 10.1093/jbcr/irz145.
Vital, genetically engineered, porcine xenografts represent a promising alternative to human cadaveric allografts (HCA) in the treatment of severe burns. However, their clinical value would be significantly enhanced if preservation and long-term storage-without the loss of cellular viability-were feasible. The objective of this study was to examine the direct impact of cryopreservation and the length of storage on critical in vivo and in vitro parameters, necessary for a successful, potentially equivalent substitute to HCA. In this study, vital, porcine skin grafts, continuously cryopreserved for more than 7 years were compared side-by-side to otherwise identically prepared skin grafts stored for only 15 minutes. Two major histocompatibility complex (MHC)-controlled donor-recipient pairs received surgically created deep-partial wounds and subsequent grafting with split-thickness porcine skin grafts, differentiated only by the duration of storage. Clinical and histological outcomes, as well as quantification of cellular viability via a series of 3-4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) assays, were assessed. No statistically significant differences were observed between skin grafts cryopreserved for 15 minutes vs 7 years. Parametric distinctions between xenografts stored for short- vs long-term durations could not be ascertained across independent clinical, histological, or in vitro evaluative methods. The results of this study validate the ability to reliably preserve, store, and retain the essential metabolic activity of porcine tissues after cryopreservation. Plentiful, safe, and readily accessible inventories of vital xenografts represent an advantageous solution to numerous limitations associated with HCA, in the treatment of severe burns.
有生命力的、经过基因工程改造的猪异种移植物代表了一种有前途的替代人体尸体同种异体移植物(HCA)的方法,可用于治疗严重烧伤。然而,如果可以实现保存和长期储存而不丧失细胞活力,它们的临床价值将大大提高。本研究的目的是研究冷冻保存和储存时间对关键的体内和体外参数的直接影响,这些参数是成功替代 HCA 的必要条件。在这项研究中,连续冷冻保存超过 7 年的有生命力的猪皮移植物与仅储存 15 分钟的其他相同制备的皮移植物进行了并排比较。两个主要组织相容性复合体(MHC)控制的供体-受体对接受了手术造成的深部部分伤口,并随后用厚度为的猪皮移植物进行了移植,这些移植物的区别仅在于储存时间。通过一系列 3-4,5-二甲基噻唑-2-基]-2,5 二苯基四氮唑溴盐(MTT)测定评估了临床和组织学结果以及通过一系列 3-4,5-二甲基噻唑-2-基]-2,5 二苯基四氮唑溴盐(MTT)测定评估了细胞活力的定量。在冷冻保存 15 分钟与 7 年的皮移植物之间未观察到统计学上的显著差异。在独立的临床、组织学或体外评估方法中,无法确定短时间和长时间储存的异种移植物之间的参数差异。本研究的结果验证了在冷冻保存后可靠地保存、储存和保留猪组织基本代谢活性的能力。大量、安全且易于获得的有生命力的异种移植物库存为治疗严重烧伤时与 HCA 相关的许多限制提供了有利的解决方案。