Response to a Comment on “Scar‐Degrading Endothelial Cells as a Treatment for Advanced Liver Fibrosis”

Abstract

David Dolivo et al. recently shared their views regarding our study on in vitro primed endothelial cells, which were capable of degrading scars. The authors proposed that the current treatment strategy for fibrosis should be broadened to involve other cell types, stimuli, elements of the extracellular matrix (ECM) and targeted organ types. Transcriptomic profiles have been specified as an effective resource for predicting cells with the capability to degrade the ECM. The authors were also concerned if the ECMdegradation therapy for fibrosis would be accomplished in other organs (e.g., cardiac fibrosis), which did not possess the same regenerative capabilities as the liver. Overall, we found these comments quite inspiring for future endeavors in cell-degradation therapy in the treatment of fibrosis in multiple organs.As liver fibrosis advances, collagen I is the most prominent ECM component. [1] We centered our study on collagen I for construction of a cell-mediated ECM-degradation screening system (CEDSS), [2] whereas other ECM components such as fibronectin, elastin, and collagen III were absent. In the future, CEDSS needs to be further improved to tailor the concentration of collagen I, supplement with other ECM components, and include multiple ECM crosslinking schemes [3] (e.g., lysyl oxidases, transglutaminases, and advanced glycation end products) according to the characteristics of pathological ECM in different fibrotic organs. This would be more bionic and effective in screening fibrotic ECM degrading cells for specialized organs.Utilizing cell type-specific transcriptomic profiles to predict cells with the capacity to break down the extracellular matrix (ECM) is a noteworthy concept. For instance, by assessing the expression of proteases related to the ECM degradation of various cell types, we can identify potential ECM-degrading cells and related regulatory mechanisms. Nevertheless, omics data of transcriptomic profiles only reveal the expression of proteases at the gene level, thus the function of ECM degradation of the cells should still be determined and validated by functional assays based on CEDSS.