Ross Edward A, Miller Madelyn H, Pacheco Allison, Willenberg Alicia R, Tigno-Aranjuez Justine T, Crawford Kaitlyn E
Department of Internal Medicine, College of Medicine, University of Central Florida, Orlando, FL, USA.
Immunity and Pathogenesis Division, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL, USA.
Clin Exp Gastroenterol. 2021 Nov 3;14:429-439. doi: 10.2147/CEG.S325945. eCollection 2021.
The pathophysiology of inflammatory bowel diseases remains poorly understood and treatment remains suboptimal for many patients. We hypothesize that the inflammatory milieu secondarily prolongs the injury and attenuates healing. We propose primary or adjuvant therapy with biocompatible adhesives to restore a barrier to protect submucosal structures, particularly stem cells.
We used the well-described mouse dextran sodium sulfate (DSS) model of colitis resembling human ulcerative colitis to test the therapeutic efficacy of intrarectal administration of the tamarind plant-derived xyloglucan (TXG) polymer adhesive which underwent extensive analytic characterization. Mice in control, DSS-only, TXG-only, and DSS + TXG groups were studied for gross (weight, blood in stool, length of colon) and multiple histologic parameters.
Compared to DSS-only mice, TXG prevented the weight loss, occurrence of blood in the stool and colon shortening, with all those parameters not being statistically different from treatment naïve animals. Histologically, there was dramatic and highly statistically significant reduction in the total inflammatory index and protection from goblet cell loss, cellular infiltration, crypt abscess formation, epithelial erosion, granulation tissue, epithelial hyperplasia crypt irregularity and crypt loss. The TXG purity and characterization were established by nuclear magnetic resonance, infrared spectroscopy, differential scanning calorimetry, and texture analysis.
The striking attenuation of disease severity by intrarectal TXG use warrants future investigations of natural bioadhesives with well-established high safety profiles, and which could potentially be derivatized to include therapeutically active moieties for local drug delivery.
炎症性肠病的病理生理学仍未被充分理解，许多患者的治疗效果仍不理想。我们假设炎症环境会继发地延长损伤并减弱愈合。我们提出使用生物相容性粘合剂进行主要或辅助治疗，以恢复屏障来保护粘膜下结构，特别是干细胞。
我们使用了已充分描述的类似于人类溃疡性结肠炎的小鼠葡聚糖硫酸钠（DSS）结肠炎模型，来测试经直肠给药的罗望子植物来源的木葡聚糖（TXG）聚合物粘合剂的治疗效果，该粘合剂经过了广泛的分析表征。对对照组、仅DSS组、仅TXG组和DSS + TXG组的小鼠进行了大体（体重、粪便带血、结肠长度）和多个组织学参数的研究。
与仅使用DSS的小鼠相比，TXG可防止体重减轻、粪便带血和结肠缩短，所有这些参数与未接受治疗的动物相比无统计学差异。在组织学上，总炎症指数显著且具有高度统计学意义的降低，并且可防止杯状细胞丢失、细胞浸润、隐窝脓肿形成、上皮糜烂、肉芽组织、上皮增生、隐窝不规则和隐窝丢失。通过核磁共振、红外光谱、差示扫描量热法和质地分析确定了TXG的纯度和特性。
经直肠使用TXG可显著减轻疾病严重程度，这值得对具有公认高安全性的天然生物粘合剂进行进一步研究，并且这些粘合剂可能被衍生化以包含用于局部药物递送的治疗活性部分。
