Introduction. Safe closure of gastric luminal defects remains a big challenge for development of gastric endoscopic surgery. The aims of this thesis are to assess the effect and efficiency of Eagle Claw VIII (endoscopic suturing device)and adipose tissue-derived mesenchymal stem cells (ADMSCs) for closure and enhancing healing of gastric luminal defects. / Methods and Results. 1. Endoscopic suturing is superior to endoclips for closure of gastrotomy after NOTES. A 2cm linear incision on the body of porcine stomach was closed by hand suturing, Eagle Claw VIII or endoclips, respectively (n=17 for each group). The results indicated that all gastrotomies were successfully closed. Closure time was significantly longer in Eagle Claw VIII group. Bursting pressure of gastrotomies for Eagle Claw VIII was significantly higher than endoclips, but lower than hand suturing. Besides, both Eagle Claw VIII and endoclip closure encountered significantly technical challenges. This study suggested that Eagle Claw VIII had potential for endoscopic closure of gastrotomies, but need further refinement. / 2. ADMSCs for Acceleration of Healing of Sutured Gastric Perforation(SGP). ADMSCs were isolated and expanded in vitro, and characterized by stromal differentiations and cell surface markers. A 2cm SGP was produced on gastric body of rats. 5×10⁶ ADMSCs were transplanted into SGP by local injection (LI-ADMSCs) or topical spraying (TS-ADMSCs). Healing of SGP was assessed. LI-ADMCs significantly decreased peritoneal adhesion and wound dehiscence, and increased bursting pressure of SGP, when comparing to other experimental groups. Histologic analysis indicated that SGPs in LI-ADMSCs group had more re-epithelialization and collagen regeneration, and less inflammation. Expression of TGF-β1 was up-regulated, while IL-6 was down-regulated in LI-ADMSCs group, when comparing to fibrin and control groups. This study suggested that local injection of ADMSCs is an effective approach for accelerating the healing of SGP. / 3. Promoting Effect of ADMSCs on Healing of Gastric Ulcer is abrogated by NSAIDs. Gastric ulcer model in rats was successfully produced by using 70% acetic acid. A total of 1×10⁷ ADMSCs was locally injected into ulcer lesion. Ulcer area was measured at different time points. Therapeutic potentialof ADMSCs was assessed when NSAIDs was simultaneously administrated. The results demonstrated that ADMSCs significantly decreased ulcer area. Histologic assessment indicated that ADMSCs increased re-epithelialization, angiogenesis and collagen deposition, and suppressed inflammation. Transplanted ADMSCs homed into gastric ulcer lesion and differentiated into endothelial and smooth muscle cells. In addition, ADMSCs treatment increased the gene expressions for wound healing, and activated COX-2-PGE₂ and Erk1/2-MAPK signaling pathways. Repeated administration of Indomethacin reduced cell proliferation and angiogenesis, and eliminated ADMSCs-induced ulcer healing on day 10. The results suggested that ADMSCs promoted the healing of peptic ulcer, which is eliminated by NSAIDs. / Conclusions. Endoscopic suturing by Eagle Claw VIII is feasible for closure of gastrotomy, when comparing to endoclips. ADMSC promotes the healing of gastric luminal defects including SGP and ulcer. The promoting effect of ADMSC is PGE₂-dependent, and attenuated by NSAIDs. These evidences implied that combined use of endoscopic suturing and ADMSCs is a helpful approach for safe closure of gastrotomy and gastric perforation. / 引言：胃傷口癒合是胃消化內鏡手術發展的障礙之壹。本課題之目的是評價和探索Eagle Claw VIII和脂肪幹細胞(ADMSCs)縫合和促進胃內傷口癒合的效果和作用。 / 方法和結果：1. 內鏡縫合器Eagle Claw VIII閉合經胃自然腔道手術後傷口的效果評價體外豬胃體上造2cm的胃傷口模型，使用手工縫合、內鏡下Eagle Claw VIII縫合或內鏡夾閉合胃傷口；每組17個樣本。本研究提示所有胃傷口均成功閉合。Eagle Claw VIII縫合胃傷口時間顯著長於其他兩組的閉合時間。Eagle Claw VIII縫合的胃傷口破裂壓顯著高於內鏡夾閉組，但是明顯低於手工縫合組。此外，內鏡縫合和夾閉都面臨較大的技術難度。本研究提示Eagle Claw VIII有臨床運用的潛在價值，但需要進壹步改進。 / 2. 局部移植脂肪幹細胞促進胃穿孔癒合的實驗性研究：建立大鼠2cm胃體穿孔模型，局部註射或傷口表面塗抹法移植ADMSCs，觀察胃傷口癒合情況。局部註射移植ADMSCs顯著減輕胃傷口粘連和裂開發生率，增加胃傷口破裂壓。組織學分析提示ADMSCs治療促進傷口上皮和肉芽組織再生，抑制炎癥反應。此外，局部註射ADMSCs增加TGF-β1抑制IL-6表達。本研究提示局部註射移植ADMSCs是促進胃穿孔傷口癒合的有效方法。 / 3. 局部移植脂肪幹細胞促進胃饋瘍癒合的實驗性研究：使用70%醋酸建立大鼠胃體饋瘍模型；饋瘍病竈內局部註射移植1×107 ADMSCs。研究提示第10和15天ADMSCs顯著減小饋瘍面積。組織學研究提示ADMSCs增加饋瘍傷口上皮和血管再生，促進膠原蛋白分泌和抑制炎癥反應。移植的ADMSCs能夠在饋瘍病竈內成活，並分化成血管內皮細胞和平滑肌細胞。ADMSCs顯著提高促傷口癒合相關基因表達水準。此外，ADMSCs啟動COX-2-PGE2和Erk1/2-MAPK信號通路。第10天，和對照組相比，引哚美辛/ADMSCs組潰瘍病竈內細胞增殖和血管再生顯著降低、饋瘍癒合延遲。本研究提示脂ADMSCs促進胃饋瘍癒合；非甾體抗炎藥顯著減弱ADMSCs的促胃饋瘍癒合作用。 / 結論：與內鏡夾閉相比，Eagle Claw VIII內鏡縫合胃創口有可行性。ADMSCs促進胃穿孔和饋瘍癒合，且依賴於前列腺素E2；引哚美辛抑制前列腺素E2合成從而抑制ADMSCs促胃組織癒合之效能。本研究提示聯合使用內鏡縫合器和ADMSCs是促進胃傷口癒合的潛在有效方法。 / Thesis Ph.D. Chinese University of Hong Kong 2014. / Includes bibliographical references (leaves 152-162). / Abstracts also in Chinese. / Title from PDF title page (viewed on 11, October, 2016). / Liu, Liu. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_1291503 |
| Date | January 2014 |
| Contributors | Liu, Liu (author.), Lai, Bo San Paul (thesis advisor.), Chinese University of Hong Kong Graduate School. Division of Surgery. (degree granting institution.) |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, bibliography, text |
| Format | electronic resource], electronic resource, remote, 1 online resource (164 leaves) : illustrations, computer, online resource |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons "Attribution-NonCommercial-NoDerivatives 4.0 International" License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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