Organoids as Miniature Twins—Challenges for Comparability and Need for Data Standardization and Access

Round 1

Reviewer 1 Report

This Concept Paper is very interesting for proposing an open data platform to address the issue of authenticity and persistent comparability of organoids, preserving their ethical information. The writing is very clear and well structured. Minor comments are as follows:

• The use of hPSCreg database for registering organoids has the advantage of using an existing platform. However, it might not be easy to find organoids among so many hPSC cell lines. An explanation about how this will be solved is necessary, such as promoting keywords or suggesting hPSCreg to include a separate line for organoids.
• Challenges for organoids to recapitulate the patient's response to drugs should be briefly reviewed.
• Examples of common protocols for growing and maintaining organoids should be briefly reviewed. 
• "Protocolls" in Figure 1 should be "protocols". 

Author Response

• The use of hPSCreg database for registering organoids has the advantage of using an existing platform. However, it might not be easy to find organoids among so many hPSC cell lines. An explanation about how this will be solved is necessary, such as promoting keywords or suggesting hPSCreg to include a separate line for organoids.

Thank you for this comment, and indeed this may be one of the main challenges for the proposed platform. We have included a relevant paragraph in the manuscript (page 10/11). 

• Challenges for organoids to recapitulate the patient's response to drugs should be briefly reviewed (page 7).

This is an interesting aspect, a paragraph was included in the manuscript. 

• Examples of common protocols for growing and maintaining organoids should be briefly reviewed.

While this point is extremely relevant and interesting for the community, a list of the various protocols would go beyond the scope of this review. We have instead included in the text that refers to the importance of making protocols available through the platform in a structured way (page 10/11).

• "Protocolls" in Figure 1 should be "protocols".

Corrected.

Reviewer 2 Report

Personalized organoid models have broad application prospects in the field of studying developmental or pathological processes, drug development or toxicity screening, tissue engineering, gene editing, personalized disease model. However, the widespread application of organoid models in future practice faces several barriers including reproducibility, comparability, and standardization. The authors proposed underlying reasons for these challenges and discuss whether the human pluripotent stem cell registry (hPSCreg), an open resource on stem cell data, will contribute to disentangling these complicated topics and standardizing organoid applications. The concepts presented by the authors are of great guiding significance as the application of organoids beyond the expected future prospects requires more careful foresight, including the management of specific applications and possible social and ethical challenges.

The authors proposed that the hPSCreg (https://hpscreg.eu) may act as an established proto-type for translation into the organoid field and listed data requirements for organoid standardization in Table 1. Among them, morphology metadata include Size, Structural elements, Histology, whether these data should be more specific and informative such as the specific number of days in organoid development, whether there are more objective measurable criteria in histology, if the author can add more specific supplements, then it will be more constructive.

Author Response

• The authors proposed that the hPSCreg (https://hpscreg.eu) may act as an established proto-type for translation into the organoid field and listed data requirements for organoid standardization in Table 1. Among them, morphology metadata include Size, Structural elements, Histology, whether these data should be more specific and informative such as the specific number of days in organoid development, whether there are more objective measurable criteria in histology, if the author can add more specific supplements, then it will be more constructive.

We thank the reviewer for the comments. While provision of more specific supplements for organoid data types would be extremely valuable, we believe it is a community task. We have therefore added a paragraph on how the stakeholder community should be involved to define standards and data needed for organoid assessment (page 6).