Utilizing Human Dermal Fibroblast Heterogeneity in Autologous Dermal Fibroblast Therapy: An Overcomplicated Strategy or a Promising Approach?

Abstract

Although human dermal fibroblast heterogeneity has been acknowledged for several decades and a large body of in vitro studies has been performed with zonal dermal fibroblast, current autologous dermal fibroblast therapies do not reflect human dermal fibroblast heterogeneity. To determine if the utilization of human dermal fibroblast heterogeneity in autologous dermal fibroblast therapy is more of a translational perspective that may thus be more likely to make it to the clinic, this article critically reviews the previous studies on dermal fibroblast heterogeneity performed to date. We found that in vitro studies of human dermal fibroblast heterogeneity have run nearly parallel to the in vivo study of autologous dermal fibroblast therapy. Although several human to nude mice xenotransplantation experiments have been performed in different layers of human dermal fibroblast, their clinical significance remains to be considered. We conclude that there is still a great gap between basic experiments and the clinical employment of human dermal fibroblast heterogeneity. To overcome this, it is necessary to conduct clinical trials, which might be restricted by ethical issues. Alternatively, it might be easier to conduct in vivo studies in animal models. Based on our previous study of dermal fibroblast heterogeneity in pigs, we propose the use of pigs as a good animal model for dermal fibroblast heterogeneity. Time will show whether the utilization of human dermal fibroblast heterogeneity in autologous dermal fibroblast therapy is an overcomplicated strategy or a promising approach. Anat Rec, 302:2126–2131, 2019. © 2019 American Association for Anatomy

Papillary and reticular fibroblasts generate distinct microenvironments that differentially impact angiogenesis

“…We and others suggested that papillary fibroblasts are more pro-angiogenic compared to reticular (Sorrell et al 2008a;Nauroy et al 2017). However, the lack of physiologically relevant in vivo models has limited the understanding of the molecular and cellular mechanisms underlying these processes (Philippeos et al 2018;Zuo et al 2019). In vitro models are being extensively used but mostly consist in 2D cell monolayers or 3D hydrogels made of exogenous proteins (Sorrell et al 2004;Mine et al 2008;Varkey et al 2013).…”