Differential Contribution of Dermal Resident and Bone Marrow–Derived Cells to Collagen Production during Wound Healing and Fibrogenesis in Mice

Abstract

Recent studies show that bone marrow (BM)-derived cells migrating into a dermal wound promote healing by producing collagen type I. However, their contribution to the repair process has not been fully verified yet. It is also unclear whether BM-derived cells participate in dermal fibrogenesis. We have addressed these issues using transgenic mice that harbor tissue-specific enhancer/promoter sequences of α2(I) collagen gene linked to either enhanced green fluorescent protein (COL/EGFP) or the luciferase (COL/LUC) reporter gene. Following dermal excision or subcutaneous bleomycin administration, a large number of EGFP-positive collagen-producing cells appeared in the dermis of COL/EGFP reporter mice. When wild-type mice were transplanted with BM cells from transgenic COL/EGFP animals and subjected to dermal excision, no EGFP-positive BM-derived collagen-producing cells were detected throughout the repair process. Luciferase assays of dermal tissues from COL/LUC recipient mice also excluded collagen production by BM-derived cells during dermal excision healing. In contrast, a limited but significant number of CD45-positive collagen-producing cells migrated from BM following bleomycin injection. These results indicate that resident cells in the skin are the major source of de novo collagen deposition in both physiological and pathological conditions, whereas BM-derived cells participate, in part, in collagen production during dermal fibrogenesis.

Pharmacological activation of cannabinoid 2 receptor attenuates inflammation, fibrogenesis, and promotes re-epithelialization during skin wound healing

“…There is a controversy on whether or not fibrocytes participate in skin wound repair. A few experiments revealed that no fibrocyte was detected during skin wound healing (Barisic-Dujmovic et al, 2010;Higashiyama et al, 2011). However, many others certified the recruitment of fibrocytes after skin injury (Ishii et al, 2005;Mori et al, 2005;Ou et al, 2015;Suga et al, 2014).…”

Fibroblasts and myofibroblasts in wound healing

“…It is generally accepted that the major source of myofibroblasts are local connective tissue fibroblasts that are recruited into the wound 30. Dermal fibroblasts located at the edges of the wound can acquire a myofibroblastic phenotype and participate in tissue repair 31.…”

Fibroblast heterogeneity: implications for human disease

“…This population of fibroblasts have the capacity to differentiate into multiple lineages (23) and have been termed mesenchymal stem or stromal cells (MSCs). Initial reports suggested that MSCs can contribute to the dermis (24)(25)(26), but subsequent studies do not appear to support this finding (27)(28)(29). Interestingly, clinical trials have suggested that the infusion of MSCs into the blood may ameliorate several diseases, such as graft-versus-host disease (30,31).…”