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利用干细胞衍生的肠道类器官打造肠道健康再生医学的未来。

Engineering the Future of Regenerative Medicines in Gut Health with Stem Cell-Derived Intestinal Organoids.

作者信息

Kumar Dinesh, Gupta Sonia, Gupta Vrinda, Tanwar Rajni, Chandel Anchal

机构信息

School of Pharmacy, Desh Bhagat University, Mandi Gobindgarh, Punjab, India.

Swami Devi Dyal Group of Professional Institute, Panchkula, India.

出版信息

Stem Cell Rev Rep. 2025 May 17. doi: 10.1007/s12015-025-10893-w.

Abstract

The advent of intestinal organoids, three-dimensional structures derived from stem cells, has significantly advanced the field of biology by providing robust in vitro models that closely mimic the architecture and functionality of the human intestine. These organoids, generated from induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs), or adult stem cells, possess remarkable capabilities for self-renewal, differentiation into diverse intestinal cell types, and functional recapitulation of physiological processes, including nutrient absorption, epithelial barrier integrity, and host-microbe interactions. The utility of intestinal organoids has been extensively demonstrated in disease modeling, drug screening, and personalized medicine. Notable examples include iPSC-derived organoids, which have been effectively employed to model enteric infections, and ESC-derived organoids, which have provided critical insights into fetal intestinal development. Patient-derived organoids have emerged as powerful tools for investigating personalized therapeutics and regenerative interventions for conditions such as inflammatory bowel disease (IBD), cystic fibrosis, and colorectal cancer. Preclinical studies involving transplantation of human intestinal organoids into murine models have shown promising outcomes, including functional integration, epithelial restoration, and immune system interactions. Despite these advancements, several challenges persist, particularly in achieving reproducibility, scalability, and maturation of organoids, which hinder their widespread clinical translation. Addressing these limitations requires the establishment of standardized protocols for organoid generation, culture, storage, and analysis to ensure reproducibility and comparability of findings across studies. Nevertheless, intestinal organoids hold immense promise for transforming our understanding of gastrointestinal pathophysiology, enhancing drug development pipelines, and advancing personalized medicine. By bridging the gap between preclinical research and clinical applications, these organoids represent a paradigm shift in the exploration of novel therapeutic strategies and the investigation of gut-associated diseases.

摘要

肠道类器官是由干细胞衍生而来的三维结构,它通过提供能够紧密模拟人类肠道结构和功能的强大体外模型,极大地推动了生物学领域的发展。这些类器官由诱导多能干细胞(iPSC)、胚胎干细胞(ESC)或成体干细胞生成,具有显著的自我更新能力、分化为多种肠道细胞类型的能力,以及对生理过程(包括营养吸收、上皮屏障完整性和宿主 - 微生物相互作用)进行功能重现的能力。肠道类器官的实用性已在疾病建模、药物筛选和个性化医疗中得到广泛证明。显著的例子包括iPSC衍生的类器官,已被有效地用于模拟肠道感染;以及ESC衍生的类器官,为胎儿肠道发育提供了关键见解。患者来源的类器官已成为研究针对炎症性肠病(IBD)、囊性纤维化和结直肠癌等疾病的个性化治疗和再生干预的有力工具。涉及将人类肠道类器官移植到小鼠模型中的临床前研究已显示出有前景的结果,包括功能整合、上皮修复和免疫系统相互作用。尽管取得了这些进展,但仍存在一些挑战,特别是在实现类器官的可重复性、可扩展性和成熟度方面,这阻碍了它们在临床上的广泛应用。解决这些限制需要建立类器官生成、培养、储存和分析的标准化方案,以确保研究结果的可重复性和可比性。尽管如此,肠道类器官在改变我们对胃肠道病理生理学的理解、加强药物开发流程和推进个性化医疗方面具有巨大潜力。通过弥合临床前研究与临床应用之间的差距,这些类器官代表了探索新型治疗策略和研究肠道相关疾病的范式转变。

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