Talk:WikiJournal of Medicine/Impact of xenogenic mesenchymal stem cells secretome on a humoral component of the immune system

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--Athikhun.suw (discuss • contribs) 00:26, 2 January 2023 (UTC)


 * Dear colleagues!
 * We finalized the manuscript of the article in accordance with the recommendations of the reviewers. All recommendations were taken into account (perhaps the reviewers will consider that we have not fully taken into account them, but we have carefully worked out all the issues). I am attaching a list of improvements made:
 * Refinement of the manuscript taking into account the review 1
 * Material and methods
 * 1) We have attached a photo of cells differentiated in three directions. We added information about the identification of mesenchymal stem cells.
 * 2) We have added information about experimental animals (including species, sex, age and body weight).
 * 3) We have clarified the methodology for modeling secondary immunodeficiency in mice, and corrected technical errors.
 * 4) We have clarified the methodology for calculating AFC.
 * Refinement of the manuscript taking into account the review 2
 * Introduction
 * 1)               We have added literature data on the immunobiological properties of the MSCs.
 * Material and methods
 * 2)               We have specified the FBS origin used in this study.
 * 3)               We have included speed and time for centrifugation.
 * 4)               We`ve attached a photo of cells differentiated in three directions. We added information about the identification of mesenchymal stem cells.
 * 5)               We have added information about cell density of MSCs seeded for secretome preparation.
 * 6)               We have clarified secretome preparation methods.
 * 7)               We have described a method for measuring the proteins in this study.
 * 8)               We have clarified the methodology for modeling secondary immunodeficiency in mice, and corrected technical errors.
 * Results
 * 9)               We have explained the results linking with figures
 * 10)             The sentence “As for the hemagglutinin (HA) titers, the control and reference drug were on the same level by this indicator.” was corrected.
 * 11)            The sentence "the intramuscular route of administration also turned out to be more effective than the subcutaneous one.” has been clarified with p-value; we have added a link on figure.
 * 12)            We have clarified dose dependence of the observed effects on the humoral arm of immunity with statistical analysis data.
 * 13)            We have explained why we had decided to test the survival rate, FCA count, and HA titer in mice with secondary immunodeficiency in the minimal concentration.
 * 15)            We have added revised illustrations.
 * Discussion
 * 14)            We have explained and discussed more about the recusing effect of the secretome in secondary immunodeficiency mice.
 * 16)            We have marked the most important parameters of humoral immunity in our opinion with justification.
 * 17)            We have discussed more references to support the effect of xenogeneic MSCs on the humoral immune response, but we have not found literature sources about such effects of secretome.
 * We ask you to forward the revised manuscript for final consideration
 * Sincerely, Vitalii Moskalov Vitalii moskalov (discuss • contribs) 04:18, 15 May 2023 (UTC)

Tech Editor Comment
I noticed that the spelling of "mesenchimal", while consistent with many published papers, is not consistent with the Wikipedia spelling, which is with a Y, mesenchymal. Should this be kept as the author stated it, or use the more common/Wikipedia standard spelling?

Additionally, consider adding redirects for both spellings. Treenxorr (discuss • contribs) 11:46, 8 February 2023 (UTC)


 * The authors do not object to writing the term "mesenchimal" through "Y" (as "mesenchymal"), but we don't know how to fix the title of the article in the "Wiki" system. Vitalii moskalov (discuss • contribs) 17:51, 27 April 2023 (UTC)

Peer review 3
--Athikhun.suw (discuss • contribs) 11:05, 28 June 2023 (UTC)


 * 1) What strain of mice were used (not specified).
 * The study was performed on outbred white adult mice, as indicated in the manuscript. Unfortunately, the researchers did not have the financial and logistical ability to purchase mice of certain strains. We can consider these mice as "wild type" or the supplier's own population of mice.
 * 2) What do the panels in Figure 1 indicate (no legend).
 * Figure 1 depicts a three-line differentiation of MSCs (in osteogenic, adipogenic, and chondrogenic directions) as a stage in cell culture identification. A detailed description of the figure is given in the corresponding section (Section "File description"):
 * The capacity of the mesenchymal stem cells (used in the study to obtain the secretome) to differentiate into three lines:
 * 1 - osteogenic differentiation (1a - control, undifferentiated cells (no differentiation inducer added); 1b - osteocytes, calcium deposits stained with Alizarin red dye, x100); 2 - adipogenic differentiation (2a - control, undifferentiated cells (no differentiation inducer added); 2b - adipocytes, fat deposits stained with Oil Red, x100); 3 - chondrogenic differentiation (3a - control, undifferentiated cells (no differentiation inducer added); 3b - chondrocytes, glycosaminoglycans stained with Alcian blue dye, x100)
 * Perhaps this legend should be placed elsewhere. Please indicate where this needs to be done.
 * 3) There is mention of randomization without a randomization procedure (classic mistake in these kinds of studies).
 * Randomization was done by urn design taking into account the body weight of the animals (the deviation in the initial weight of animals did not exceed 10%).
 * We have clarified this information to the "Materials and Methods" section.
 * 4) What number of animals were used in each experiment? (not specified).
 * ·      n = 6 (experiment in mice with normal immune status);
 * ·      n = 10 (experiment in mice with secondary immunodeficiency at the beginning of the experiment);
 * ·      Taking into account the survival rate in the groups, there were such an end-point number of animals: Positive control – 0 animals; Negative control – 10 animals; “Thymalin” – 4 animals; “10 µl i/m” – 5 animals; “10 µl s/c” – 5 animals.
 * We have added this information to the "Materials and Methods" section.
 * 5) Why was a Mann-Whitney test used as some kind of post-test on multigroup data and not ANOVA?
 * At the first stage, the Kruskal-Wallis test (ANOVA) was applied. At the significance level p≤0.001, the null hypothesis about the equality of the samples was rejected. However, this statistical method indicates the presence of a statistically significant difference between groups, but does not indicate between which groups this difference is significant. Therefore, at the second stage, the groups were compared in pairs using the Mann-Whitney (Wilcoxon) U test.
 * We have added this information to the manuscript.
 * 6) Why are there no statistics on the survival data, and at which time point was this gauged?
 * Samples were administered 5 days prior to the modeling of immunodeficiency and until the indicators were taken into account. Immunization with a 3% suspension of freshly washed ram erythrocytes was carried out for 4 days, starting from the next day after modeling the pathology. Accounting for survival was carried out before determining the amount of AFC and antibody titer on the next day after the completion of immunization (5th day after the administration of HCA) by taking into account the number of animals that had died by this time.
 * We have added this information to the manuscript.
 * Statistical analysis of survival was performed, as indicated in the manuscript, using the Fisher test for sample shares. A significant increase in survival compared to the positive control was found. Differences in this indicator between experimental groups and negative control, as well as between different experimental groups, are not significant (as indicated in the manuscript). Vitalii moskalov (discuss • contribs) 11:31, 28 June 2023 (UTC)

Editor comments
One of our board - Eric Youngsrtrom - says:

I have reviewed the author responses in more depth than the paper.

Two thoughts on the responses, both small: (a) it seems that characterizing the mice as “supplier's own population of mice” seems most precise, though I defer to others with more expertise whether “wild type” is appropriate.

(b) The statistical methods are both non-parametric alternatives to the ones asked about in Review 3 (ANOVA, t-test). Presumably there was a reason or advantage to using nonparametric methods (non-normal distribution of dependent variable, or outliers, are the two most likely). Kruskal Wallis and Mann-Whitney are good non-parametric options, so the choice is not a problem, but the *rationale* for the choice is still missing (and without a rationale, ANOVA would usually be preferable because of familiarity and a slight statistical power advantage).

I would recommend acceptance with minor revision that clarifies those two points. Rwatson1955 (discuss • contribs) 11:55, 20 July 2023 (UTC)

Editor comment
Eric A Youngstrom comments:

I commend the authors on a thorough and helpful response! The description of the mice is sufficiently detailed, and the logic for the selection of non-parametric tests is clear and appropriate. In fact, it follows best practices (the other good alternative would have been trying transformations to make the normality assumption tenable). One final point of clarification – I think that the authors used Fisher’s exact test for the proportions. Fisher developed multiple different statistical methods, so adding that one word ensures certainty about the choice of method.

Kudos on a strong piece of work! Rwatson1955 (discuss • contribs) 08:54, 28 July 2023 (UTC)