Breaking and Remaking: Using Organoids to Model Gastric Tissue Damage and Repair

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Summary

This paper reviews the use of gastroids as models to study damage and repair processes in the stomach and explore their applications and limitations in mimicking in vivo gastric tissue repair. Gastroids can be generated from adult stem cells (ASCs) or pluripotent stem cell (PSCs). They recapitulate cell-type diversity of the stomach and spatial organization, though limited by the lack of mesenchyme, nerves and immune cells. Applications of gastroids include modeling disease (e.g. H. pylori infection), drug screening (e.g. cancer therapy) and developmental studies. Current gastroids limitations include modeling inflammatory microenvironments and capturing regenerative cues seen in vivo. Improvements of gastroids may involve co-culture systems.

 

General comments

The review is informative and relevant to the nascent application of using gastroids to study damage and repair in the stomach. However, this review requires minor revisions to reach its purpose, as mentioned by the authors in the introduction section:

The manuscript would benefit from a reorganization of its sections. Indeed, sections 4, 5 and 6 present the basics of gastric biology and related terms that are necessary to understand gastric organoids in sections 3 and 4. Therefore, sections 4, 5 and 6 should arrive before sections 3 and 4.

The authors should expand their discussion on gastroid-based damage and repair to fully reach the aim of their work. Indeed, much of the content focuses on general characteristics of gastroids, development protocols, their ability to recapitulate cellular diversity and spatial organization. However, discussions specific to tissue damage and restitution/regeneration are sparse and scattered throughout the manuscript. Moreover, there’s limited discussion on regenerative signaling, in vivo relevance or long-term repair modeling.

Specific comments

Title

To better reflect the content, the authors could revise the title to clarify its stomach-specific scope. Indeed, the title suggests a broad focus on gastrointestinal organoids, but the review focuses on gastroids rather than the entire gastrointestinal tract.

Introduction

The manuscript would benefit from a short sentence defining organoids, gastroids, colonoids to improve clarity and to avoid confusion to newly introduced readers. 

The authors should clearly explain their rationale in reviewing specifically adult gastric organoids in tissue damage and repair.

Gastric organoids as an elevated model system

The authors can improve the clarity and flow of sentences from line 50 to 54.

This section would benefit from specific examples of applications on gastroids cultures that led to important discoveries in the gastric field.

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors The manuscript entitled “Breaking and Remaking: Using Organoids to Model Gastroin-2 testinal Tissue Damage and Repair” is an interesting topic. However, there are still several parts that need to be revised: 1. The article provides a detailed overview of the application of gastric organoids in simulating gastrointestinal tissue damage and repair, covering multiple aspects such as the construction of gastric organoids, stem cell dynamics, microenvironment regulation, and disease models. However, some of the content (such as the construction method of gastric organoids) has a high degree of similarity with existing literature. It is suggested to further highlight the innovative points of this article in the discussion, such as exploring the application of gastric organoids in radiation injury models or analyzing the prospects of multicellular organoids. 2. The overall structure of the article is clear, but some sections (such as the "Gastric Stem Cells" section) are quite lengthy. It is recommended to streamline or split them to improve readability. In addition, charts (such as Figure 1 and Table 1) are helpful for understanding the content, but some of the chart annotations are not detailed enough. It is recommended to supplement legend explanations or details of key experimental conditions. 3. The article cites a large number of literature to support the argument, but some key conclusions (such as the role of Troy+cells in injury repair) lack direct experimental data citations. It is recommended to supplement relevant research results or clearly label them as hypotheses. In addition, the latest research (such as literature published in 2024) has not been fully included, and it is recommended to update the references to reflect the progress in the field. The culture conditions for gastric organoids (such as growth factor combinations) are listed in Table 1, but there is a lack of specific concentration or supplier information, which may affect the reproducibility of the experiment. Suggest providing detailed parameters of key reagents or citing publicly available standardized protocols. The article emphasizes the application of gastric organoids in personalized medicine and drug screening, but lacks discussion on the challenges of practical clinical translation, such as large-scale cultivation of organoids and cost-benefit analysis. Suggest adding a section specifically discussing bottleneck issues and possible solutions from laboratory to clinical settings. 6. Some sentences are expressed in a lengthy manner, it is recommended to further streamline them. In addition, the format should be standardized with abbreviations (such as the full name of "Wnt" should be indicated when it first appears), and the completeness of the reference list should be checked (such as non-standard journal name abbreviations in some references).

Author Response

Please see the attachment

Author Response File: Author Response.pdf