Abstract
BackgroundAirways repair is critical to lung function following transplantation. We hypothesised that the stem cell factor (SCF) could play a role in this setting.MethodsWe studied 9 lung transplant recipients (LTx recipients) during their first year postgraft, and evaluated SCF mRNA expression in bronchial biopsy specimens using on-line fluorescent PCR and SCF protein levels in bronchoalveolar lavage (BAL) and serum using ELISA. The expression of SCF receptor Kit was assessed using immunostaining of paraffin-embedded bronchial sections.ResultsSCF mRNA was highly expressed during the early postgraft period [Month (M)1-M3] (300% increase vs controls: 356 vs 1.2 pg SCF/μg GAPDH cDNA, p < 0.001) and decreased thereafter (M4-M12: 187 pg/μg), although remaining at all times 10–100 times higher than in controls. While SCF protein levels in BAL were similar in LTx recipients and in controls, the SCF serum levels were at all times higher in LTx recipients than in controls (p < 0.05), with no relationship between these levels and the acute complications of the graft. Finally, Kit was strongly expressed by the mast cells as well as by the bronchial epithelium of LTx recipients.ConclusionSCF and Kit are expressed in bronchial biopsies from lung transplant recipients irrespective of the clinical status of the graft. A role for these factors in tissue repair following lung transplantation is hypothesised.
Highlights
Airways repair is critical to lung function following transplantation
stem cell factor (SCF) mRNA High levels of SCF mRNA expression were observed in the airways of every lung transplant recipient
This expression was marked during the early post-transplant period (M1-M3), when it was 300% of the level in controls (356 pg SCF/μg GAPDH in patients and 1.2 pg SCF/μg GAPDH mRNA in controls, p < 0.001) (Figure 1)
Summary
Airways repair is critical to lung function following transplantation. We hypothesised that the stem cell factor (SCF) could play a role in this setting. Experimental studies in murine models provide evidence that bone marrow stem cells can differentiate into type I and type II pneumocytes and bronchial epithelial cells [5,7] The ability of such cells to engraft into the human lung is still controversial studies after hematopoietic stem cell transplantation in humans show evidence of donor-derived cells (chimerism) in the lung [8,9]. There is some evidence for the involvement of local progenitor cells in repair processes following tissue injury in murine models [11,12,13] as well as in human situations [14,15]. The SCF/Kit pathway has been shown to play a key role in these latter
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