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Fibroblasts are the main cell type in the dermis. They are responsible for the synthesis and deposition of structural proteins such as collagen and elastin, which are integrated into the extracellular matrix (ECM). Mouse and human studies using flow cytometry, cell culture, skin reconstitution, and lineage tracing experiments have shown the existence of different subpopulations of fibroblasts, including papillary fibroblasts, reticular fibroblasts, and fibroblasts comprising the dermal papilla at the base of the hair follicle. In recent years, the technological advances in single-cell sequencing have allowed researchers to study the repertoire of cells present in full-thickness skin including the dermis. Multiple groups have confirmed that distinct fibroblast populations can be identified in mouse and human dermis on the basis of differences in the transcriptional profile. Here, we discuss the current state of knowledge regarding dermal fibroblast heterogeneity in healthy mouse and human skin, highlighting the similarities and differences between mouse and human fibroblast subpopulations. We also discuss how fibroblast heterogeneity may provide insights into physiological wound healing and its dysfunction in pathological states such as hypertrophic and keloid scars.

Preprints enable new forms of peer review that have the potential to be more thorough, inclusive, and collegial. In December 2022, 80 researchers and representatives of funders, institutions, preprint servers, journals, indexers, and review services were invited to gather online and at the Janelia Research Campus for a workshop on Recognizing Preprint Peer Review. Sponsored by HHMI, ASAPbio, and EMBO, this meeting aimed to catalyze community consensus and support for preprint peer review and to create model funder, institutional, and journal policies that recognize both preprints with reviews, and reviews of preprints. Here, we make a call to action to stakeholders in the community to help capture the growing momentum of preprint sharing and empower researchers to provide open and constructive peer review for preprints.

The angiotensin-converting enzyme 2 (ACE2) receptor mediates uptake of SARS-CoV-2, the virus responsible for COVID-19. Previous work analyzing publicly available bulk RNA-sequencing data sets has shown the expression of ACE2 in human keratinocytes. This finding is potentially relevant for the etiology of COVID-19-associated rashes and might also suggest a possible entry mechanism for the SARS-CoV-2 virus. In this study, the authors examined the spatial localization of ACE2 mRNA in vivo.The authors analyzed several publicly available single-cell RNA-sequencing data sets. They determined spatial localization of ACE2 mRNA using multiplex RNA in situ hybridization in human skin.Both analyses supported ACE2 expression in keratinocytes and skin vasculature, which could reflect a potential cutaneous entry point for SARS-CoV-2, particularly in damaged or broken skin. Moreover, ACE2 expression in vascular endothelial cells may support direct, virally mediated mechanisms in the etiology of the chilblain-like acral eruption that is seen in patients with COVID-19.

Scars caused by burns, chronic ulcers from diabetes, infections, skin cancer surgery, and other genetic or somatic disease could require effective treatment to avoid functional and psychological troubles and even mortality. Most of the current treatments aim to reduce local inflammation but not to prevent scarring. Herein, we discussed about emerging technologies in scar management using allogeneic cell therapy. The industrialised allogeneic cell therapy products and the clinical trials using keratinocytes, fibroblasts or MSCs demonstrated acceleration of skin cell migration and proliferation, control wound scarring, immunomodulatory properties and improved angiogenesis. In addition, allogeneic cell transplants offered the possibility of large pre-fabrication, cryo-preservation, for instantaneous use and repeated applications. Current research exploring allogeneic cell therapies for scar treatment are focusing on grafting of epidermal sheets, cellular dermal substitutes and reconstructed skin equivalent and cell intradermal injections. Advances in knowledge in therapeutic potentials of allogeneic injected cells give rise to new therapeutic approaches such as administration of allogeneic cell-derived extracellular vesicles.

The purpose of this chapter was to provide an overview and potential answers to the ethical considerations of the clinical scar management. Here, we focused on two main aspects. The first aspect was to discuss the need to invoke ethics when the clinician is faced to a patient’s scar. The second aspect was to discuss the clinicians dilemmas in their daily practice when they are managing a patient’s scar.

Patients with recessive dystrophic epidermolysis bullosa (RDEB) lack type VII collagen and therefore have severely impaired dermal-epidermal stability causing recurrent skin and mucosal blistering. There is currently no specific approved treatment for RDEB. We present preclinical data showing that intradermal injections of genetically corrected patient-derived RDEB fibroblasts using a Good Manufacturing Practices grade self-inactivating COL7A1 retroviral vector reverse the disease phenotype in a xenograft model in nude mice. We obtained 50% transduction efficiency in primary human RDEB fibroblasts with an average low copy number (range = 1–2) of integrated provirus. Transduced fibroblasts showed strong type VII collagen re-expression, improved adhesion properties, normal proliferative capabilities, and viability in vitro. We show that a single intradermal injection of 3 × 10 6 genetically corrected RDEB fibroblasts beneath RDEB skin equivalents grafted onto mice allows type VII collagen deposition, anchoring fibril formation at the dermal-epidermal junction, and improved dermal-epidermal adherence 2 months after treatment, supporting functional correction in vivo. Gene-corrected fibroblasts previously showed no tumorigenicity. These data show the efficacy and safety of gene-corrected fibroblast therapy using a self-inactivating vector that has now been good manufacturing grade-certified and pave the way for clinical translation to treat nonhealing wounds in RDEB patients.