Incorporating Immune Cells into Organoid Models: Essential for Studying Human Disease
Round 1
Reviewer 1 Report
The manuscript by Bogoslowski et al. presents possible methods of incorporating immune cells into organoids. The authors discuss the immune microenvironment in organoid development by incorporating immune cells in an organoid model.
As the authors discuss in the manuscript, many groups have developed organoid tissue for functional assay.
In human disease, resident or migrated immune cells may also regulate cellular functions
—the authors briefly overview the current technique and incorporation of immune cells.
The reviewed manuscript is well structured and emphasizes the primary information of organoid models with immune cells. The references are appropriate, and figures are acceptable for publication.
Author Response
Thank you for your comments. Attached is the updated version.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
INCORPORATING IMMUNE CELLS INTO ORGANOID MODELS: ESSENTIAL FOR STUDYING HUMAN DISEASE
The authors discuss the current state of organoids and their potential in the biomedical field, while outlining the need for incorporation of immune cells in these backed by sufficient evidence. I congratulate the authors for the vision of their work as I think this is absolutely necessary for enhancing the rate of success in clinical trials.
While the content of their article is excellent – it needs to be checked and certain sentences need to be rephrased in scientific English to emphasise on their points of the need for addition of immune cells to organoids. Please get it edited by someone in the field who is fluent in scientific writing in English or by MDPI services – especially the abstract, introduction and conclusion section to make the article stronger. Rest of the sections need minor checking. It is not wrong English, it just needs to framed better so that the article has the impact you set out to achieve.
Once again, well done and all the best ?
Minor suggestions:
1. Please mention the type of manuscript (article/review/perspective etc) on top left corner as indicated in the format
2. Please indicate the corresponding author with an * against their name
3. For your entire text – please number the sections and sub-sections
4. In the introduction – near line 53 where you mention that most organoid studies do not consider immune cells, please add 2-3 lines as why that is the case? Does it complicate the already complicated organoids? Are they currently harder to culture/maintain with the rest of the cell populations? Etc.
5. Figure 1: ILC – has been abbreviated much later in the text, it needs to be done before or in the figure. Please add innate lymphoid cells before ILC to make it easier to read.
6. Figure 2 – please check the font size of the figure legend
7. For your section titled ‘Incorporating immune cells into organoids: Methods and discoveries’ – it will be very useful to have a table of the studies that have included immune cells in their organoids. You can do this with the following columns of a. Organoid system (target organ/scaffold), b. immune cells used c. method used for incorporating immune cells, d. outcome of adding immune cells and e. reference. You may also add studies from tumor section and add the table after the tumor section as a summary of the studies you have discussed in both the sections.
8. Please add relevant reference in your section titled ‘ sources of immune cells’ to back up your statement with evidence.
9. In future outlook when you talk about the limitations of organoids – please do not ignore factors like a. lack of uniformity of organoid fabrication for a tissue within the scientific community due to the absence of solid protocols, b. Challenges faced in adapting vascularity in organoids, especially for those associated with bone and bone marrow and c. donor variation in cells and thus in the organoids attempted with donor derived cells.
10. Line 463-464, reference number 72 – what was successful about this organoid? Currently unclear. Please add 2-3 line about it or remove it completely.
11. Please add references at the end of each sentence between lines 470-480. Currently it is just statements, need some references to make it solid.
12. Please add a few more lines (4-5 more lines) to the conclusion to tie in all of your thoughts for this work with a strong take home message.
13. For funding – please add the full form for CIHR
Grammatical and language suggestions:
14. English language check is needed; for eg line 14 – more ‘physiologically relevant models’ reads better than the current play of words, line 24 and 61 should be - ‘human diseases’
15. Line 39 – change limitations to ‘challenges’
16. Please rephrase ‘For millions of years, tissue physiology has therefore developed synergistic interactions with the immune system’ to the following sentence: ‘Thus, tissue physiology has developed closely synergistic interactions with the immune system’
17. Please add full forms of RANKL, MCS-F, TNFa, PPAR-g, IGF-1, IFN-g, SIRT, IL-6, TGFb before abbreviating them in the text
18. Please check the font of lines 205-207 and font colour of lines 349-353
19. Please check grammar over all
Moderate editing of English language required
Author Response
Please see attachment.
Author Response File: Author Response.pdf
