Efficacy of Cell-Based Therapies for Traumatic Brain Injuries
, Emily G. Fellows 1,†, Winston L. Guo 1, William J. Swanson 1, Andrew T. Crane 1, Maxim C. Cheeran 2, Walter C. Low 1,3 and Andrew W. Grande 1,3,*Round 1
Reviewer 1 Report
This is a nice, concise overview of the use of cellular therapies for TBI. It covers pre-clinical and early clinical applications of the approach. I would suggest adding a few sections for completeness:
There is a recent publication in J Neurotrauma on the use of B-Cell therapies by Sirbulescu et al. that supports previous work by Hearn and Offner on the reparative nature of B-cells in stroke and TBI. This area should be covered. There is a growing idea that T regulatory cells may be a useful adjunct in reducing neuroinflammation, and this could be part of the same added section. I think that the reference 12 is a critical one (Ramlackansingh et al.,) as I think it is driving the concept of targeting microglial activation and using this imaging modality - would add to this section publications: Savitz, et al., Stem Cells 34: 537-542, 2016; Cox et al., Transfusion, 59(S1) 858-868, 2019.Author Response
Reviewer 1:
We would like to thank the reviewer for taking the time to evaluate our manuscript.
Point 1: There is a recent publication in J Neurotrauma on the use of B-Cell therapies by Sirbulescu et al. that supports previous work by Hearn and Offner on the reparative nature of B-cells in stroke and TBI. This area should be covered. There is a growing idea that T regulatory cells may be a useful adjunct in reducing neuroinflammation, and this could be part of the same added section.
Response 2: A section on the role and use of immune cells, specifically B cells and regulatory T cells, in treatment of TBI has been added.
Point 2: I think that the reference 12 is a critical one (Ramlackansingh et al.,) as I think it is driving the concept of targeting microglial activation and using this imaging modality - would add to this section publications: Savitz, et al., Stem Cells 34: 537-542, 2016; Cox et al., Transfusion, 59(S1) 858-868, 2019.
Response 2: A line specifying microglia as a target for monitoring and modulating the neuroinflammatory response has been added as well as the recommended publications Savitz, et al., Stem Cells 34: 537-542, 2016 and Cox et al., Transfusion, 59(S1) 858-868, 2019.
Reviewer 2 Report
The authors have prepared an excellent brief review of the potential value of stem cell therapy of traumatic brain injury. Several minor comments follow:
The first sentence in the Introduction requires a citation -- presumably reference 1. The sentence on line 67 of page 2 should begin a new paragraph, which would then continue with the content of the paragraph that currently begins on line 70. The discussion of MSCs emphasizes bone-marrow-derived cells and umbilical-vein-derived cells, which could lead readers to conclude that those are the only sources. Although studied less, criculating human stem cells have demonstrated efficacy in a rodent model of TBI (Nichols JE et al. Stem Cell Res Ther 2013;4:3) and represent an autologous source for human treatment. Peripheral fat also represents a source of autologous stem cells.
Author Response
We would like to thank the reviewer for taking the time to evaluate our manuscript.
Point 1: The first sentence in the Introduction requires a citation -- presumably reference 1.
Response 1: The appropriate citation has been added to the first sentence.
Point 2: The sentence on line 67 of page 2 should begin a new paragraph, which would then continue with the content of the paragraph that currently begins on line 70.
Response 2: The sentence on line 67 of page two has been moved so that it now serves as the lead in for the following paragraph.
Point 3: The discussion of MSCs emphasizes bone-marrow-derived cells and umbilical-vein-derived cells, which could lead readers to conclude that those are the only sources. Although studied less, circulating human stem cells have demonstrated efficacy in a rodent model of TBI (Nichols JE et al. Stem Cell Res Ther 2013;4:3) and represent an autologous source for human treatment. Peripheral fat also represents a source of autologous stem cells.
Response 3: At the start of the “Mesenchymal Stem Therapies for TBI” section, material has been added noting that MSC are found in most tissues and can be isolated from an array of sources. At the end of the “Mesenchymal Stem Cell Therapies for TBI” section, details on peripheral blood-derived MSC and their use in treating TBI rat models has been added.
Reviewer 3 Report
None
Author Response
We would like to thank the reviewer for taking the time to evaluate our manuscript.
The reviewer had no comments or suggestions for the authors to address and so we have no additional responses to provide.
