
上海交通大学学报(医学版) ›› 2026, Vol. 46 ›› Issue (8): 997-1006.doi: 10.3969/j.issn.1674-8115.2026.08.001
• 前沿述评 • 下一篇
收稿日期:2026-01-09
接受日期:2026-04-08
出版日期:2026-08-28
发布日期:2026-08-28
通讯作者:
于颖彦,教授,博士;电子信箱:ruijinhospitalyyy@163.com。作者简介:第一联系人:杨蕊馨撰写并修改论文,于颖彦审阅论文。所有作者均阅读并同意最终稿件的提交。
基金资助:Received:2026-01-09
Accepted:2026-04-08
Online:2026-08-28
Published:2026-08-28
Contact:
Yu Yingyan, E-mail: ruijinhospitalyyy@163.com.About author:First author contact:The manuscript was drafted and revised by Yang Ruixin, and reviewed by Yu Yingyan. Both authors have read the final version of paper and consented to its submission.
Supported by:摘要:
类器官作为新型体外三维培养模型,凭借其高度自组织能力,可以很好地还原其来源组织的形态结构、病理生理功能、基因变异谱系以及药物治疗反应性。与传统的动物模型相比,类器官具有制备周期短、成本低、伦理争议小和通量高等特点,目前被广泛应用于生物医药研究。患者源性类器官模型保留了其来源组织的异质性,可以体外长期扩增传代培养,且低温冻存复苏后依然保持细胞活力,这为人类疾病建模提供了宝贵的平台,并在发病机制探索、新型药物筛选及药物敏感性预测中展现出重要的应用价值。而人工智能(artificial intelligence,AI)的介入加速了类器官构建与应用的自动化与标准化进程。该文系统总结了消化系统良恶性疾病相关类器官研究进展,尤其是不同器官组织源性类器官构建的优化方案,并就消化系统肿瘤样本采集方法、新辅助治疗对类器官构建的影响等进行分析。此外,文章还概述了AI算法在类器官构建及应用中的进展,包括AI辅助的类器官形态表征、细胞活力评估、药物敏感性预测,以及整合AI的自动化类器官平台建设现状。展望未来,AI将在消化系统疾病类器官构建与多种应用场景中发挥重要作用,为疾病建模、分子靶点发现、药物筛选、耐药机制解析等转化应用提供强有力的支撑。
中图分类号:
杨蕊馨, 于颖彦. 消化系统疾病类器官的构建应用及其与人工智能整合的研究进展[J]. 上海交通大学学报(医学版), 2026, 46(8): 997-1006.
Yang Ruixin, Yu Yingyan. Research progress in the construction and application of digestive system disease organoids and their integration with artificial intelligence[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026,(8): 997-1006.
| Site | Biomarker | Differential diagnosis |
|---|---|---|
| Esophagus | KRT5, KRT14 | Squamous epithelium: KRT5 Glandular epithelium (such as Barrett esophagus): CDX2, MUC2, KRT20 |
| Stomach | TFF1, MUC5AC, MUC6, MUC2, KRT8 | Surface epithelium: TFF1 Fundic and corpus gland: MUC6, PGC, ATP4A Basal stem cell: LGR5 Endocrine cell: CHGA, CHGB, SCG5 |
| Intestine | EPCAM, KRT20, CDX2 | Duodenum: SLC5A1, CYP3A4 Jejunum: SLC6A19, LCT Ileum: IL22RA1, SLC10A2 Colon: CA2, MUC4 |
| Liver and bile duct | KRT7, KRT19 | Liver: ALB, AAT, TTR, APOA2 Bile duct: KRT7, KRT19, SOX9 |
| Pancreas | Endocrine and exocrine glands have different marker genes | Exocrine gland: PRSS1, CPA1, KRT19 Endocrine gland: CHGA, INS, GCG |
表1 消化系统不同部位上皮组织类器官的细胞鉴定标志物
Tab 1 Cell identification markers for organoids derived from different sites of the digestive system
| Site | Biomarker | Differential diagnosis |
|---|---|---|
| Esophagus | KRT5, KRT14 | Squamous epithelium: KRT5 Glandular epithelium (such as Barrett esophagus): CDX2, MUC2, KRT20 |
| Stomach | TFF1, MUC5AC, MUC6, MUC2, KRT8 | Surface epithelium: TFF1 Fundic and corpus gland: MUC6, PGC, ATP4A Basal stem cell: LGR5 Endocrine cell: CHGA, CHGB, SCG5 |
| Intestine | EPCAM, KRT20, CDX2 | Duodenum: SLC5A1, CYP3A4 Jejunum: SLC6A19, LCT Ileum: IL22RA1, SLC10A2 Colon: CA2, MUC4 |
| Liver and bile duct | KRT7, KRT19 | Liver: ALB, AAT, TTR, APOA2 Bile duct: KRT7, KRT19, SOX9 |
| Pancreas | Endocrine and exocrine glands have different marker genes | Exocrine gland: PRSS1, CPA1, KRT19 Endocrine gland: CHGA, INS, GCG |
| Sample origin | Sample size | Sample collection requirement | Note |
|---|---|---|---|
| Surgical resection | 200 mg (approximately the size of 2 soybeans) | Selecting vascular-rich, soft tissue; avoiding central necrotic areas tissues with marked fibrosis, large adipose aggregates, hard consistency, electrocoagulation artifacts, or yellowish-gray discoloration | Optimizing enzymatic digestion time for pancreatic cancer organoids to suppress excessive stromal cell growth |
| Needle biopsy | 3 pieces | Maximizing cell retention and minimizing cell damage during sample processing and digestion | Magnifying endoscopy can be employed for sample collection to ensure high tumor purity and avoid necrotic areas in specimens |
| Malignant ascites | 50‒100 mL | Collecting sufficient ascites, harvesting cells via centrifugation, and preparing a single-cell suspension after red blood cell lysis | Excess immunocytes can be removed by Ficoll gradient centrifugation |
表2 消化系统肿瘤类器官构建中肿瘤样本采集注意事项
Tab 2 Precautions for tumor sample collection in the organoid construction of digestive system tumor
| Sample origin | Sample size | Sample collection requirement | Note |
|---|---|---|---|
| Surgical resection | 200 mg (approximately the size of 2 soybeans) | Selecting vascular-rich, soft tissue; avoiding central necrotic areas tissues with marked fibrosis, large adipose aggregates, hard consistency, electrocoagulation artifacts, or yellowish-gray discoloration | Optimizing enzymatic digestion time for pancreatic cancer organoids to suppress excessive stromal cell growth |
| Needle biopsy | 3 pieces | Maximizing cell retention and minimizing cell damage during sample processing and digestion | Magnifying endoscopy can be employed for sample collection to ensure high tumor purity and avoid necrotic areas in specimens |
| Malignant ascites | 50‒100 mL | Collecting sufficient ascites, harvesting cells via centrifugation, and preparing a single-cell suspension after red blood cell lysis | Excess immunocytes can be removed by Ficoll gradient centrifugation |
图1 消化系统疾病类器官构建中AI应用示意图Note: Both benign and malignant tissues of the digestive system can be used for organoid construction and research. Malignant tumor samples have diverse origins. AI algorithms can assist in organoid viability evaluation, drug sensitivity prediction, and phenotypic classification.
Fig 1 Schematic diagram of AI applications in organoid construction for digestive system diseases
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