Reply to "Commentaries on the publication entitled: 'Structure and distribution of an unrecognized interstitium in human tissues' by Benias et al. (2018)

ABSTRACT

We appreciate the time and attention paid to our paper by Prof. Mestres-Ventura and similarly appreciate the opportunity to respond to his concerns. We would like to address what we believe are several fundamental misunderstandings in his commentary.1. Scale The most significant misunderstanding is one of scale. The schematic (Fig. 1) provided by Prof. Mestres-Ventura is (per personal communication) at the nano scale, while in vivo microscopy of extrahepatic bile duct and dermis shows that the collagen bundles we report are at the micron scale, each containing many individual fibrils at the nanometer scale. Indeed, examining the tissues described in our paper - submucosae, dermis and subcutaneous fascia - fresh in resected specimens or intraoperatively, we find that the structures we describe are visible at the macroscopic level (if one leans in closely enough). In other words, they are macroscopic, not microscopic. Prof. Mestres-Ventura, in summarizing the prior pCLE work of Wallace and Fockens, which he notes is similar to ours, states "the 'holes' shown under intravital microscopy and in cryofixed samples are huge (over 20 µm)" This is exactly our point - we were surprised as well at the scale of these structures, as this has not been well appreciated in the past

RESUMEN

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