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微创处理的自体基质血管成分(SVF)局部应用可减轻炎症并改善胆-胆吻合口完整性。

Local Application of Minimally Manipulated Autologous Stromal Vascular Fraction (SVF) Reduces Inflammation and Improves Bilio-Biliary Anastomosis Integrity.

作者信息

Klabukov Ilya, Shatveryan Garnik, Bagmet Nikolay, Aleshina Olga, Ivanova Elena, Savina Victoria, Gilmutdinova Ilmira, Atiakshin Dmitry, Ignatyuk Michael, Baranovskii Denis, Shegay Peter, Kaprin Andrey, Eremin Ilya, Chardarov Nikita

机构信息

Department of Regenerative Medicine, National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, Koroleva st. 4, 249036 Obninsk, Russia.

Petrovsky National Research Centre of Surgery, Abrikosovsky per. 2, 119991 Moscow, Russia.

出版信息

Int J Mol Sci. 2024 Dec 30;26(1):222. doi: 10.3390/ijms26010222.

Abstract

Bilio-biliary anastomosis (BBA) is a critical surgical procedure that is performed with the objective of restoring bile duct continuity. This procedure is often required in cases where there has been an injury to the extrahepatic bile ducts or during liver transplantation. Despite advances in surgical techniques, the healing of BBA remains a significant challenge, with complications such as stricture formation and leakage affecting patient outcomes. The stromal vascular fraction (SVF), a heterogeneous cell population derived from adipose tissue, has demonstrated promise in regenerative medicine due to its rich content of stem cells, endothelial progenitor cells, and growth factors. The objective of this study was to evaluate the potential of locally administered autologous SVF to enhance the healing of BBAs. Bilio-biliary anastomosis was performed on a swine model (female Landrace pigs). Six swine were divided into two groups: the treatment group ( = 3) received a local application of autologous SVF around the anastomosis site immediately following BBA formation, while the control group ( = 3) received saline. The primary outcomes were assessed over an eight-week period post-surgery, and included anastomosis healing, stricture formation, and bile leakage. Histological analysis was performed to evaluate fibrosis, angiogenesis, and inflammation. Immunohistochemistry was conducted to assess healing-related markers (CD34, α-SMA) and the immunological microenvironment (CD3, CD10, tryptase). The SVF-treated group exhibited significantly enhanced healing of the BBA. Histological examination revealed increased angiogenesis and reduced fibrosis in the SVF group. Immunohistochemical staining demonstrated higher vascular density in the anastomosed area of the SVF-treated group (390 vs. 210 vessels per 1 mm, = 0.0027), as well as a decrease in wall thickness (1.9 vs. 1.0 mm, = 0.0014). There were no statistically significant differences in mast cell presence ( = 0.40). Immunohistochemical staining confirmed the overexpression of markers associated with tissue repair. Local injections of autologous SVF at the site of BBA have been demonstrated to significantly enhance healing and promote tissue regeneration. These findings suggest that SVF could be a valuable adjunctive therapy in BBA surgery, potentially improving surgical outcomes. However, further investigation is needed to explore the clinical applicability and long-term benefits of this novel approach in clinical practice as a minimally manipulated cell application.

摘要

胆管-胆管吻合术(BBA)是一种关键的外科手术,其目的是恢复胆管的连续性。在肝外胆管受损的情况下或肝移植过程中,通常需要进行此手术。尽管手术技术有所进步,但BBA的愈合仍然是一项重大挑战,诸如狭窄形成和渗漏等并发症会影响患者的治疗结果。基质血管成分(SVF)是一种源自脂肪组织的异质性细胞群,由于其富含干细胞、内皮祖细胞和生长因子,在再生医学中已显示出前景。本研究的目的是评估局部应用自体SVF增强BBA愈合的潜力。在猪模型(雌性长白猪)上进行胆管-胆管吻合术。将6头猪分为两组:治疗组(n = 3)在BBA形成后立即在吻合部位周围局部应用自体SVF,而对照组(n = 3)接受生理盐水。在术后八周内评估主要结局,包括吻合口愈合、狭窄形成和胆汁渗漏。进行组织学分析以评估纤维化、血管生成和炎症。进行免疫组织化学以评估愈合相关标志物(CD34、α-SMA)和免疫微环境(CD3、CD10、类胰蛋白酶)。SVF治疗组的BBA愈合明显增强。组织学检查显示SVF组的血管生成增加且纤维化减少。免疫组织化学染色显示SVF治疗组吻合区域的血管密度更高(每1mm有390个血管对210个血管,P = 0.0027),并且壁厚减小(1.9mm对1.0mm,P = 0.0014)。肥大细胞存在方面无统计学显著差异(P = 0.40)。免疫组织化学染色证实了与组织修复相关标志物的过表达。已证明在BBA部位局部注射自体SVF可显著增强愈合并促进组织再生。这些发现表明SVF可能是BBA手术中有价值的辅助治疗方法,有可能改善手术结果。然而,需要进一步研究以探索这种新方法作为一种微创细胞应用在临床实践中的临床适用性和长期益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b79/11720677/0fa6592c43b1/ijms-26-00222-g001.jpg

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