Qayyum Abbas Ali, Lund Thomas Kromann, Jensen Pia Bredahl, Jensen Kristine, Haack-Sørensen Mandana, Ekblond Annette, Nørgaard Morten Juhl, Møller-Sørensen Hasse, Mathiasen Anders Bruun, Møller Christian Holdflod, Rørvig Sara Bird, Kalhauge Anna, Bruunsgaard Helle, Litman Thomas, Johansen Ellen Mønsted, Højgaard Lisbeth Drozd, Kastrup Jens, Perch Michael
Cardiology Stem Cell Centre, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Department of Cardiology, Hvidovre hospital, University of Copenhagen, Copenhagen, Denmark.
JHLT Open. 2025 Mar 20;8:100254. doi: 10.1016/j.jhlto.2025.100254. eCollection 2025 May.
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.
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.
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.
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.
EudraCT number 2019-004848-30 and NCT04714801.
原发性移植肺功能障碍（PGD）在肺移植中很常见，影响15%至30%的受者。它代表移植后72小时内移植肺的多因素损伤。我们旨在研究异体脂肪组织来源的间充质干细胞（ASCs）作为双肺移植患者附加治疗的临床安全性和有效性。
单中心、双盲、研究者发起的随机I/II期研究，在肺移植后两小时内静脉输注ASCs或安慰剂。共纳入31例患者，按1:1:1随机分为2亿或1亿个ASCs组或安慰剂输注组。主要终点是移植后72小时各组间PGD分级的差异。
肺移植后72小时，3组间PGD无显著差异（P = 0.426）。与安慰剂组相比，联合ASCs组移植后72小时PGD无差异（P = 0.252）。观察到接受ASC治疗的患者与安慰剂组患者相比，从第1天到第3天以及从第2天到第3天PGD进展有所降低（分别为P = 0.034和P = 0.034）。各组间严重不良事件数量或肾功能、肺功能或生活质量等次要终点无显著差异。
双肺移植后立即给患者静脉输注异体ASCs是安全的。该治疗在肺移植后72小时各组间PGD上未显示出统计学差异。
欧洲药品管理局临床试验编号2019-004848-30和美国国立医学图书馆临床试验注册编号NCT04714801。
