Transplantation Surgery Department, Institute for Clinical and Experimental Medicine (IKEM), Videnska 1958/9, 14021 Prague, Czech Republic.
Department of Biomaterials and Tissue Engineering, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic.
Int J Mol Sci. 2022 Mar 18;23(6):3310. doi: 10.3390/ijms23063310.
Background: Cardiovascular surgery is confronted by a lack of suitable materials for patch repair. Acellular animal tissues serve as an abundant source of promising biomaterials. The aim of our study was to explore the bio-integration of decellularized or recellularized pericardial matrices in vivo. Methods: Porcine (allograft) and ovine (heterograft, xenograft) pericardia were decellularized using 1% sodium dodecyl sulfate ((1) Allo-decel and (2) Xeno-decel). We used two cell types for pressure-stimulated recellularization in a bioreactor: autologous adipose tissue-derived stromal cells (ASCs) isolated from subcutaneous fat of pigs ((3) Allo-ASC and (4) Xeno-ASC) and allogeneic Wharton’s jelly mesenchymal stem cells (WJCs) ((5) Allo-WJC and (6) Xeno-WJC). These six experimental patches were implanted in porcine carotid arteries for one month. For comparison, we also implanted six types of control patches, namely, arterial or venous autografts, expanded polytetrafluoroethylene (ePTFE Propaten® Gore®), polyethylene terephthalate (PET Vascutek®), chemically stabilized bovine pericardium (XenoSure®), and detoxified porcine pericardium (BioIntegral® NoReact®). The grafts were evaluated through the use of flowmetry, angiography, and histological examination. Results: All grafts were well-integrated and patent with no signs of thrombosis, stenosis, or aneurysm. A histological analysis revealed that the arterial autograft resembled a native artery. All other control and experimental patches developed neo-adventitial inflammation (NAI) and neo-intimal hyperplasia (NIH), and the endothelial lining was present. NAI and NIH were most prominent on XenoSure® and Xeno-decel and least prominent on NoReact®. In xenografts, the degree of NIH developed in the following order: Xeno-decel > Xeno-ASC > Xeno-WJC. NAI and patch resorption increased in Allo-ASC and Xeno-ASC and decreased in Allo-WJC and Xeno-WJC. Conclusions: In our setting, pre-implant seeding with ASC or WJC had a modest impact on vascular patch remodeling. However, ASC increased the neo-adventitial inflammatory reaction and patch resorption, suggesting accelerated remodeling. WJC mitigated this response, as well as neo-intimal hyperplasia on xenografts, suggesting immunomodulatory properties.
心血管外科面临着缺乏合适的补丁修复材料的问题。去细胞动物组织是一种很有前途的生物材料的丰富来源。我们的研究目的是探索脱细胞或再细胞化的心包膜基质在体内的生物整合。
使用 1%十二烷基硫酸钠(1)同种异体脱细胞和(2)异种脱细胞)对猪(同种异体)和羊(异种,异种移植物)的心包膜进行脱细胞处理。我们在生物反应器中使用两种细胞类型进行压力刺激再细胞化:从猪的皮下脂肪中分离的自体脂肪组织来源的基质细胞(ASCs)(3)同种异体 ASC 和(4)异种 ASC)和同种异体 Wharton's 果冻间充质干细胞(WJCs)(5)同种异体 WJC 和(6)异种 WJC)。将这 6 个实验性补丁植入猪颈动脉 1 个月。作为对照,我们还植入了 6 种对照补丁,即动脉或静脉同种异体移植物、膨体聚四氟乙烯(ePTFE Propaten® Gore®)、聚对苯二甲酸乙二醇酯(PET Vascutek®)、化学稳定化牛心包(XenoSure®)和解毒猪心包(BioIntegral® NoReact®)。通过流量测定、血管造影和组织学检查评估移植物。
所有移植物均与宿主组织良好整合,无血栓、狭窄或动脉瘤形成的迹象。组织学分析显示,动脉同种异体移植物类似于天然动脉。所有其他对照和实验性补丁均发生新生内膜增生(NIH)和新生内膜增生(NIH),内皮衬里存在。XenoSure®和 Xeno-decel 上的 NAI 和 NIH 最为明显,NoReact®上的则最少。在异种移植物中,NIH 的发展程度如下:Xeno-decel > Xeno-ASC > Xeno-WJC。同种异体 ASC 和 Xeno-ASC 中的 NIH 和补丁吸收增加,而同种异体 WJC 和 Xeno-WJC 中的则减少。
在我们的研究中,植入前用 ASC 或 WJC 接种对血管补丁重塑有一定影响。然而,ASC 增加了新生内膜炎症反应和补丁吸收,提示加速了重塑。WJC 减轻了这种反应,以及异种移植物上的新生内膜增生,提示其具有免疫调节特性。