First‐in‐human high‐cumulative‐dose stem cell therapy in idiopathic pulmonary fibrosis with rapid lung function decline

Stem Cells Translational Medicine

Victor Lesnyak¹  Olesya Danilevskaya¹  Alexey Nikitin¹  Mikhail Konoplyannikov¹  Vladimir Baklaushev¹  Veronika Revkova¹  Alexander Averyanov¹  Irina Koroleva¹  Vladimir Kalsin¹  Anna Sotnikova¹  Svetlana Kotova² 

[1] Federal Research and Clinical Center of Federal Medical‐Biologic Agency Moscow Russia;Institute for Regenerative Medicine I. M.Sechenov First Moscow State Medical University Moscow Russia;

关键词: adult human bone marrow;    adult stem cells;    bone marrow stromal cells;    cellular therapy;    clinical trials;    lung;   

DOI  :  10.1002/sctm.19-0037

来源: DOAJ

【 摘 要 】

Abstract Previous phase I studies demonstrated safety and some beneficial effects of mesenchymal stem cells (MSCs) in patients with mild to moderate idiopathic pulmonary fibrosis (IPF). The aim of our study was to evaluate the safety, tolerability, and efficacy of a high cumulative dose of bone marrow MSCs in patients with rapid progressive course of severe to moderate IPF. Twenty patients with forced ventilation capacity (FVC) ≥40% and diffusing capacity of the lung for carbon monoxide (DLCO) ≥20% with a decline of both >10% over the previous 12 months were randomized into two groups: one group received two intravenous doses of allogeneic MSCs (2 × 108 cells) every 3 months, and the second group received a placebo. A total amount of 1.6 × 109 MSCs had been administered to each patient after the study completion. There were no significant adverse effects after administration of MSCs in any patients. In the group of MSC therapy, we observed significantly better improvement for the 6‐minute walk distance in 13 weeks, for DLCO in 26 weeks, and for FVC in 39 weeks compared with placebo. FVC for 12 months in the MSCs therapy group increased by 7.8% from baseline, whereas it declined by 5.9% in the placebo group. We did not find differences between the groups in mortality (two patients died in each group) or any changes in the high‐resolution computed tomography fibrosis score. In patients with IPF and a rapid pulmonary function decline, therapy with high doses of allogeneic MSCs is a safe and promising method to reduce disease progression.

【 授权许可】

Unknown