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

Abstract

We recently read Zhao et al. [1] with great interest. In this report, the authors describe a unique and intriguing method to screen for cells with substantial collagenase activity, followed by extensive characterization of these cells' ability to degrade fibrotic extracellular matrix (ECM) in a murine model in vivo and in human samples ex vivo. We believe that the authors should be commended for the novelty and depth of the work presented here, and we are particularly excited about the potential for translation of this approach to other types of fibrosis.Fibrosis is a nonregenerative repair process by which damaged, formerly functional tissue is replaced with a collagenous, mechanically aberrant scar. As a pathophysiological outcome of myriad disease states of multiple tissues, fibrosis can lead to damage and loss-of-function in numerous organs including the liver, skin, lung, kidney, and heart. Due to the variety of clinical conditions that can manifest as development of tissue fibrosis, frequently cited statistics estimate that nearly half of deaths in the industrialized world may be attributed to fibrosis. [2] Therefore, the need for therapeutic modalities to prevent and treat fibrosis is paramount, though success in clinical translation of antifibrotic pharmacologic therapies has been disappointing. Another potential treatment strategy is to deliver therapeutic cells, but this is complicated by the challenge of selecting appropriate cells with the potential to prevent or reverse fibrosis, as well as to deliver these cells effectively and efficiently to the tissue of interest.In Zhao et al., [1] the authors aimed to select a source of cells with a high degree of collagenase activity to be used as a cellular therapy to degrade liver collagen in an advanced stage hepatic fibrosis model in vivo. The authors initially performed a high-throughput screen for collagenase activity by seeding various preparations of cells into a collagen matrix pretagged with rhodamine, such that fluorescence of the culture supernatant could be used as a proxy for collagenase activity. In their initial screen, the authors found notably elevated collagenase activ-