Modelling a Human Blood-Brain Barrier Co-Culture Using an Ultrathin Silicon Nitride Membrane-Based Microfluidic Device
, Molly C. McCloskey 2, Sandra Vergo 3, Søren Christensen 3, James L. McGrath 2 and Morten S. Nielsen 1,*Round 1
Reviewer 1 Report
This manuscript entitled “Modelling a human blood-brain barrier co-culture using an ultrathin silicon nitride membrane-based microfluidic device” by Diana Hudecz et al. describes the development of a stem cell based human in vitro blood-brain barrier model. The study looks interesting because delivering drug candidates to the brain is hindered by the blood brain barrier (BBB), which makes the treatment of neurological and neurodegenerative diseases particularly challenging. The study is comprehensive with solid in vitro cell line-based analysis. This model will be useful for high-resolution in situ imaging and for studying receptor mediated transport and transcytosis in a physiological barrier. All experiments to answer the relevant questions were undertaken. In summary, I recommend this manuscript for acceptance in International Journal of Molecular Sciences.
Author Response
Thank you for your kind and fast evaluation of our manuscript. We appreciated your words and comments. The new version of the manuscript addresses Reviewer 2's comments (changes are in Section 2.1)
Reviewer 2 Report
This manuscript “Modelling a human blood-brain barrier co-culture using an ultrathin silicon nitride membrane-based microfluidic device” describes an iBMECs and microdevice based blood-brain barrier model. The trafficking of two monoclonal antibodies were investigated to demonstrate the model. The experimental methods were sufficiently described. The manuscript is well written. I have a few minor comments.
1. What is the differentiation of the model used in this study compared to the other cell-based μSiM models described in previous literature ([27-30])?
2. It would be helpful to include a brief description of the five differentiation protocols in the main manuscript.
3. The antibodies mAb#52 and 15G11 hIgG1 do not cross the blood-brain barrier model used in this study. How can the model be potentially optimized to improve the permeability?
Author Response
Thank you for the kind and fast evaluation of our manuscript. We apricated your comments and have now amended the manuscript accordingly. We hope you find the new version acceptable for publication. The point-by-point response to your comments can be found in the attachment.
Author Response File: 
Author Response.pdf
