[CITATION][C] Fibroblasts of recipient origin contribute to airway fibrosis in murine tracheal transplantations

C Konoeda, J Nakajima, T Murakawa - Transplant International, 2015 - Wiley Online Library
C Konoeda, J Nakajima, T Murakawa
Transplant International, 2015Wiley Online Library
Dear Sirs, Bronchiolitis obliterans (BO) is a major limitation in the long-term success of lung
transplantation. BO is characterized as fibrotic obliterations in small airways [1]. Fibroblasts
are the key players in fibrosis. They produce extracellular matrix components, and those
deposition results in fibrosis. The source of fibroblasts in transplanted organs is an
unresolved question. Determining the origin of airway fibroblasts is considered to be a key
step in establishing ways to prevent fibrosis. According to previous reports [2–4], three …
Dear Sirs, Bronchiolitis obliterans (BO) is a major limitation in the long-term success of lung transplantation. BO is characterized as fibrotic obliterations in small airways [1]. Fibroblasts are the key players in fibrosis. They produce extracellular matrix components, and those deposition results in fibrosis. The source of fibroblasts in transplanted organs is an unresolved question. Determining the origin of airway fibroblasts is considered to be a key step in establishing ways to prevent fibrosis. According to previous reports [2–4], three possible sources of fibroblasts in transplanted organs are recipient bone marrow cells [2], regional fibroblasts in the grafts [3], or transitioned donor cells that had undergone epithelial to mesenchymal transition (EMT)[4]. In this study, we investigated whether fibroblasts in rejected airways originated from donor or recipient cells using orthotopic tracheal transplantation (OTT) and heterotopic tracheal transplantation (HTT) mouse models with transgenic C57Bl/6 mice that ubiquitously expressed green fluorescent protein (GFP)(B6-Tg (GFP)). Subepithelial fibrosis in OTT allografts [5] and intraluminal fibrosis in HTT allografts [6] are observed on or after the 28th day. All animals received humane care in compliance with the ‘Guide for Animal Experimentation, University of Tokyo, revised 2007’and the ‘Act on Welfare and Management of Animals’ published by Japanese ministry. All of the mice were purchased from Japan SLC, Inc. BALB/c and B6-Tg (GFP) female mice were used as donors or recipients. The heterotopic and orthotopic tracheal transplantations were performed under the operating microscope as previously reported [5, 6]. For HTT, the donor tracheas were placed into the subcutaneous space of the anterior neck area.
Wiley Online Library