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脂肪组织来源的间充质干细胞与富血小板血浆混合用于炎症性肠吻合口愈合的有效性:大鼠的一项临床前研究

The Effectiveness of Adipose Tissue-Derived Mesenchymal Stem Cells Mixed with Platelet-Rich Plasma in the Healing of Inflammatory Bowel Anastomoses: A Pre-Clinical Study in Rats.

作者信息

Geropoulos Georgios, Psarras Kyriakos, Papaioannou Maria, Geropoulos Vasileios, Niti Argyri, Nikolaidou Christina, Koimtzis Georgios, Symeonidis Nikolaos, Pavlidis Efstathios T, Koliakos Georgios, Pavlidis Theodoros E, Galanis Ioannis

机构信息

2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece.

Laboratory of Biological Chemistry, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.

出版信息

J Pers Med. 2024 Jan 22;14(1):121. doi: 10.3390/jpm14010121.

Abstract

Multiple factors have been linked with increased risk of anastomotic leak in bowel surgery, including infections, inflammatory bowel disease, patient comorbidities and poor surgical technique. The aim of this study was to investigate the positive effect, if any, of adipose derived mesenchymal stem cells (MSCs) mixed with platelet-rich plasma (PRP) in the healing of bowel anastomoses, in an inflammatory environment after establishment of experimental colitis. Thirty-five male Wistar rats were divided into five groups of seven animals: normal controls, colitis controls, PRP, MSCs, and PRP+MSCs. All groups underwent laparotomy, one-cm segmental colectomy and anastomosis in situ. In the colitis group, colectomy was performed at the affected area. Colitis was previously established by transrectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) except for the normal controls. Post-mortem histopathological, tissue hydroxyproline and anastomotic bursting pressure (ABP) assessments were performed. The Mann-Whitney U test was used to assess statistical significance differences between groups. No perioperative mortality was noted. Tissue hydroxyproline and ABP were significantly increased in the group of PRP+MSCs compared to colitis controls ( = 0.0151 and = 0.0104, respectively). Inflammatory cell infiltration was lower and fibroblast activity higher in PRP+MSCs group, but not statistically significant ( > 0.05). Neoangiogenesis ( = 0.0073) and anastomotic area epithelialization ( = 0.0182) were significantly higher in PRP + MSCs group compared to colitis controls. The synergistic effect of the PRP and MSCs is apparently responsible for the improved healing markers in bowel anastomoses even on inflammatory bowel. This gives hope for primary anastomoses and stoma saving in many emergency and/or elective circumstances, especially in immunocompromised or malnourished patients, even in cases with inflammation or peritonitis. Clinical studies should follow in order to support the clinical application of PRP+MSCs in gastrointestinal anastomoses.

摘要

多种因素与肠道手术吻合口漏风险增加相关,包括感染、炎症性肠病、患者合并症及手术技术欠佳。本研究旨在探讨脂肪来源间充质干细胞(MSCs)与富血小板血浆(PRP)混合使用对实验性结肠炎形成后炎症环境中肠道吻合口愈合是否有积极作用。35只雄性Wistar大鼠被分为五组,每组7只:正常对照组、结肠炎对照组、PRP组、MSCs组和PRP + MSCs组。所有组均接受剖腹手术、1厘米节段性结肠切除术及原位吻合术。在结肠炎组,结肠切除术在病变部位进行。除正常对照组外,先前通过经直肠给予2,4,6 - 三硝基苯磺酸(TNBS)建立结肠炎模型。进行了尸检组织病理学、组织羟脯氨酸及吻合口破裂压力(ABP)评估。采用曼 - 惠特尼U检验评估组间统计学显著性差异。未观察到围手术期死亡。与结肠炎对照组相比,PRP + MSCs组的组织羟脯氨酸和ABP显著增加(分别为P = 0.0151和P = 0.0104)。PRP + MSCs组的炎症细胞浸润较低,成纤维细胞活性较高,但无统计学显著性(P > 0.05)。与结肠炎对照组相比,PRP + MSCs组的新生血管形成(P = 0.0073)和吻合口区上皮化(P = 0.0182)显著更高。PRP和MSCs的协同作用显然是肠道吻合口愈合标志物改善的原因,即使是在炎症性肠病中。这为许多急诊和/或择期情况下的一期吻合和避免造口带来了希望,特别是在免疫功能低下或营养不良的患者中,甚至在有炎症或腹膜炎的病例中。应开展临床研究以支持PRP + MSCs在胃肠道吻合术中的临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/debd/10817310/47e35a2f66e4/jpm-14-00121-g001.jpg

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