Dziki Jenna L, Keane Timothy J, Shaffiey Shahab, Cognetti Dan, Turner Neill, Nagle Deborah, Hackam David, Badylak Stephen
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania.
Department of Materials, Imperial College London, London, UK.
J Surg Res. 2017 Oct;218:353-360. doi: 10.1016/j.jss.2017.06.066. Epub 2017 Jul 22.
Precancerous or cancerous lesions of the gastrointestinal tract often require surgical resection via endomucosal resection. Although excision of the colonic mucosa is an effective cancer treatment, removal of large lesions is associated with high morbidity and complications including bleeding, perforation, fistula formation, and/or stricture, contributing to high clinical and economic costs and negatively impacting patient quality of life. The present study investigates the use of a biologic scaffold derived from extracellular matrix (ECM) to promote restoration of the colonic mucosa following short segment mucosal resection. Six healthy dogs were assigned to ECM-treated (tubular ECM scaffold) and mucosectomy only control groups following transanal full circumferential mucosal resection (4 cm in length). The temporal remodeling response was monitored using colonoscopy and biopsy collection. Animals were sacrificed at 6 and 10 wk, and explants were stained with hematoxylin and eosin (H&E), Alcian blue, and proliferating cell nuclear antigen (PCNA) to determine the temporal remodeling response. Both control animals developed stricture and bowel obstruction with no signs of neomucosal coverage after resection. ECM-treated animals showed an early mononuclear cell infiltrate (2 weeks post-surgery) which progressed to columnar epithelium and complex crypt structures nearly indistinguishable from normal colonic architecture by 6 weeks after surgery. ECM scaffold treatment restored colonic mucosa with appropriately located PCNA+ cells and goblet cells. The study shows that ECM scaffolds may represent a viable clinical option to prevent complications associated with endomucosal resection of cancerous lesions in the colon.
胃肠道的癌前或癌性病变通常需要通过内镜黏膜切除术进行手术切除。尽管结肠黏膜切除术是一种有效的癌症治疗方法,但切除大的病变会导致高发病率和并发症,包括出血、穿孔、瘘管形成和/或狭窄,从而带来高昂的临床和经济成本,并对患者生活质量产生负面影响。本研究调查了一种源自细胞外基质(ECM)的生物支架在促进短节段黏膜切除术后结肠黏膜修复中的应用。6只健康犬经肛门进行全周黏膜切除(长度为4厘米)后,被分为ECM治疗组(管状ECM支架)和仅行黏膜切除术的对照组。通过结肠镜检查和活检采集来监测时间性重塑反应。在6周和10周时处死动物,将外植体用苏木精和伊红(H&E)、阿尔辛蓝和增殖细胞核抗原(PCNA)染色,以确定时间性重塑反应。对照组动物均出现狭窄和肠梗阻,切除后无新黏膜覆盖迹象。接受ECM治疗的动物术后2周出现早期单核细胞浸润,术后6周进展为柱状上皮和复杂的隐窝结构,与正常结肠结构几乎无法区分。ECM支架治疗使结肠黏膜得以修复,PCNA+细胞和杯状细胞定位恰当。该研究表明,ECM支架可能是预防结肠癌性病变内镜黏膜切除相关并发症的一种可行的临床选择。