Est1 Task 2

Task 1: Write a letter to the editor

Dear Dr Holzapfel:

After reviewing the manuscript submitted by Pearson et al., I suggest the paper to be revised before the acceptance for publication is granted.

The paper hypothesised the predictive response of cell differentiation to be mathematically represented as a function of growth factors concentration in conjunction with shear stress level in a hollow fibre membrane bioreactor (HFMB). This is the first demonstration which specifies undifferentiated and differentiated cell population in a multiphase HFMB model. In addition, the decent scientific standard of the research is demonstrated through the reasonable assumptions of threshold cell differentiation for shear stress increase, and adequate analyses of expected and resulted graphs with notes to cell cycles and yielding number. The originality is thus classed as high and the priority for publication is high.

However, there exists several major doubts. Undisclosed experimental observations,

On pages 5-6, the diffusion coefficient of growth factor in water D is quoted from literature, whilst for growth factor concentration C*, duration of cells differentiation phase T, and the cell death rate Γwn were merely taken from personal communication with an independent laboratory. The rate of cell proliferation Γnw, cell differentiation Γud, solute uptake ΓR1 and Michaelis-Menten uptake K were selected to fit experimental observations received in the same manner. These data are proven [1, 2] to deviate between cell types and in response to culture environmental variations. Authors are advised to either publish detailed experimental data in the appendices, or consult reviewed articles, then assess the sensitivity of the model to different species and perfusion