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一种用于猪模型血管化复合组织异体移植研究的创新性耳移植。

An innovative ear transplantation for vascularized composite allotransplantation research in porcine model.

作者信息

Holguín-Ruíz Jorge A, Rodríguez Laura, Ferreira-Galvao Flavio H, Muñoz-Botina Jaime, Bedoya Duque Maria Alejandra, Varela-Vásquez María Del Mar, Rodríguez-Galviz Henry, Zambrano-Galeano Rodrigo, Castaño-Valencia Santiago, Gutiérrez-Montes José Oscar

机构信息

Pharmacology Research Group, Universidad del Valle, Colombia, Cali, 760043.

School of Basic Sciences Department of Physiological Sciences, Universidad del Valle, Cali, Colombia, 760043.

出版信息

Sci Rep. 2024 Dec 28;14(1):30896. doi: 10.1038/s41598-024-81908-8.

DOI:10.1038/s41598-024-81908-8
PMID:39730666
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11680874/
Abstract

Vascularized composite allotransplantation (VCA) represents a clinical challenge for transplant therapy, as it involves different tissues with unique immunogenicity. Even when receiving immunosuppressive therapy, they are more vulnerable to severe hypoxia, microvascular damage, and ultimately the rejection or chronic graft dysfunction after transplantation. This study aimed to develop a surgical protocol for VCA of the ear in a porcine biomodel in the absence of immunosuppression, maintaining the in vitro co-culture of the allograft and assessing their relationship with allograft survival. We employed four crossbred pigs and four outbred mini pig biomodels (Sus scrofa), as donors and recipients, to perform four VCAs. Blood samples were taken from each biomodel for crossmatch testing and SLA haplotype identification. Bone marrow samples were taken from each recipient for subsequent co-culture. In vitro culture and co-culture conditions were maintained and assessed. Histological analysis using hematoxylin and eosin staining was performed on the allograft that lasted the longest time showing the smallest macroscopic signs of rejection. A surgical protocol for Vascularized Composite Allograft (VCA) ear transplantation in a porcine biomodel was developed, including the skin. The presence of SLA-DRB101:02 and SLA-DRB106:01 haplotypes in the recipient and donor, respectively, showed concordance with positive crossmatch tests. In the allograft with the highest survival time, no histological signs of hyperacute rejection were found ten days after transplantation in the anastomosis area. The results obtained from this protocol can provide valuable recommendations for translational applications in face transplantation and regenerative medicine.

摘要

血管化复合组织异体移植(VCA)对移植治疗而言是一项临床挑战,因为它涉及具有独特免疫原性的不同组织。即便接受免疫抑制治疗,它们仍更容易遭受严重缺氧、微血管损伤,最终在移植后出现排斥反应或慢性移植物功能障碍。本研究旨在制定一种在无免疫抑制情况下猪生物模型中耳部VCA的手术方案,维持同种异体移植物的体外共培养并评估它们与同种异体移植物存活的关系。我们使用四头杂交猪和四头远交小型猪生物模型(野猪)作为供体和受体,进行了四次VCA。从每个生物模型采集血样进行交叉配型检测和SLA单倍型鉴定。从每个受体采集骨髓样本用于后续共培养。维持并评估体外培养和共培养条件。对存活时间最长且排斥反应宏观迹象最小的同种异体移植物进行苏木精和伊红染色的组织学分析。制定了猪生物模型中包括皮肤的血管化复合异体移植(VCA)耳部移植的手术方案。受体和供体中分别存在SLA - DRB101:02和SLA - DRB106:01单倍型,与阳性交叉配型检测结果一致。在存活时间最长的同种异体移植物中,移植十天后在吻合区域未发现超急性排斥的组织学迹象。从该方案获得的结果可为面部移植和再生医学的转化应用提供有价值的建议。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb92/11680874/bcc2cca67c30/41598_2024_81908_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb92/11680874/5e706201baa1/41598_2024_81908_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb92/11680874/f3c57800ebef/41598_2024_81908_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb92/11680874/bcc2cca67c30/41598_2024_81908_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb92/11680874/5e706201baa1/41598_2024_81908_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb92/11680874/e16398ed94ee/41598_2024_81908_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb92/11680874/f44b2965e468/41598_2024_81908_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb92/11680874/f3c57800ebef/41598_2024_81908_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb92/11680874/bcc2cca67c30/41598_2024_81908_Fig5_HTML.jpg

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Evaluation of Early Markers of Ischemia-reperfusion Injury and Preservation Solutions in a Modified Hindlimb Model of Vascularized Composite Allotransplantation.在改良的血管化复合异体移植后肢模型中评估缺血再灌注损伤的早期标志物及保存液
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Clinical and preclinical tolerance protocols for vascularized composite allograft transplantation.
血管化复合组织异体移植的临床和临床前耐受方案。
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