Allogeneic mesenchymal stromal cell therapy on primary graft dysfunction after lung transplantation.

Background: Primary graft dysfunction (PGD) is common in lung transplantation affecting 15-30% of recipients. It represents a multifactorial injury to the transplanted lung within the first 72 hours after transplantation.We aimed to investigate clinical safety and efficacy of allogeneic adipose tissue-derived stromal cells (ASCs), as an add-on therapy in patients undergoing double lung transplantation. Methods: Single center, double-blinded, investigator-initiated randomized phase I/II study with intravenous infusion of either ASCs or placebo within two hours after lung transplantation. A total of 31 patients were included and randomized 1:1:1 to either 200 million or 100 million ASCs, or placebo infusion.The primary endpoint was difference in PGD grade 72 hours after transplantation between groups. Results: No significant differences in PGD were seen between the 3 groups 72 hours after lung transplantation (P=0.426). Combined ASC groups compared to placebo group did not show any difference in PGD 72 hours after transplantation (P=0.252). A reduced progression in PGD from day 1 to day 3 and day 2 to day 3 was observed between the ASC treated patients and patients in the placebo group (P=0.034 and P=0.034, respectively). There were no significant differences in number of serious adverse events or in secondary endpoints such as kidney function, lung function, or quality-of-life between groups. Conclusions: Intravenous infusion of allogeneic ASCs in patients immediately after double lung transplantation was safe. The therapy did not show statistic difference in PGD between groups 72 hours after lung transplantation. Clinical trial registration information: EudraCT number 2019-004848-30 and NCT04714801.