PURPOSE: Mouse orthotopic single lung transplantation (LTx) is a vital scientific model to explore lung transplantation (LTx) immunology. Minor alloantigen-mismatched LTx using C57BL/10 (B10, H-2b) to C57BL/6 (B6, H-2b) has mild acute rejection and sometimes chronic fibrosis, mimicking human LTx where alloimmunity is dampened by immunosuppressants. We have observed variations in allograft histology depending on individual microsurgeons' experience. The purpose of this study was to compare pathological variations between individual surgeons and over time. METHODS: We performed a retrospective review of B10 to B6 LTx performed in our lab and sacrificed 28 days after LTx. LTx with an experimental intervention (e.g., usage of immunomodulatory agents or knock-out mice) were excluded. All pathological grading was performed in a blinded manner using H&E and Masson-Trichrome staining. Each surgeon's first 10, middle 10, and last 10 LTx in our lab were statistically compared using two-way ANOVA. RESULTS: Data from 120 LTx were available from four surgeons' records. Pathological scores were not uniform among surgeons and tended to decrease over time (Figure 1). Inter-surgeon differences were statistically significant for every parameter except for %parenchymal fibrosis (A grade, P=0.0033; B grade, P<0.0001; % parenchymal fibrosis, P=0.1164; peri-airway fibrosis, P<0.0001; obliterative airway fibrosis, P<0.0001). Intra-surgeon chronological changes in pathological scores were statistically significant for A grade, B grade, and % parenchymal fibrosis (P=0.0024, P=0.0416, P=0.0097, respectively). CONCLUSION: Mouse single lung transplantation is one of the most technically challenging animal models. It remains a powerful model to study underlying mechanisms of LTx biology. However, the significant learning curve and surgeon-dependent variability in histopathological findings need to be taken into account when designing experimental protocols.
|Journal||The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation|
|Publication status||Published - 2020 Apr 1|
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Cardiology and Cardiovascular Medicine