Fibrin, Bone Marrow Cells and Macrophages Interactively Modulate Cardiomyoblast Fate

Round 1

Reviewer 1 Report

Manuscript describes the role of the components of extracellular matrix, bone marrow cells, and macrophages in modulation of the fate of cardiomyoblsts in the rat model. The study showed that the macrophages exposed to F-BMC (fibrin/bone marrow cells) secretome increase cardiomyoblast proliferation, decrease inflammation and infarction, reduce the fibrotic scar, and improve cardiac function.

The study is very important for developing novel therapies for cardiac repair after the myocardial infarction.

Although this is a very good paper, Figure 12 and figure 12 legend are very unclear and hard to understand. The majority of the symbols are not labeled so the reader does not know what is what, the figure and its legend have to be redone.

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

Borrego and colleagues in the original research manuscript entitled “Fibrin, Bone Marrow Cells and macrophages interactively modulate cardiomyoblast fate” investigated the effects of fibrin + BMC on macrophage phenotype switching, cardiomyoblast proliferation and infarct size. The authors concluded that BMC/fibrin-based treatment decreases infarct extent and improves cardiac function. The manuscript is well-written, the introduction is focused, and the methods are adequately detailed.  However, I have the following minor concern.

1. The abstract is very lengthy and needs to be shortened as per the journal’s guidelines (max 200 words).
2. There are some typographical errors, e.g. line 69: Deng et al, line 62: These cells, line 203: macrophages should be replaced with monocytes, line 361: RT-PCR was performed using RNA isolated from macrophages (not lysates), etc.
3. How did the authors perform the co-culture of BMC and macrophages (line 218)? Did they use transwell inserts to perform co-culture studies? Please elaborate.
4. What were the levels of pro-and anti-inflammatory cytokines in infarct and healthy heart areas?
5. It is advised to include the representative immunostaining images for Fig. S1. What are the levels of M1 macrophages in the heart tissue?
6. This reviewer does not agree with statement line 357 to 359. I do not see any differences between BMC vs F-BMC and Fibrin vs F-BMC. The observed effects could be because of fibrin only.
7. Most importantly, the authors need to include high-resolution images in all the figures. I was not able to read the figures and may need to re-review the manuscript with high-resolution figures.

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

The authors have addressed all my comments satisfactorily.