Efficacy of Wharton Jelly Mesenchymal Stromal Cells infusions in moderate to severe SARS-Cov-2 related acute respiratory distress syndrome: a phase 2a double-blind randomized controlled trial

Frontiers in Medicine

Medicine

Hélène Rousseau¹  Nadine Petitpain²  Adéle Dhuyser³  Michael Peres³  Marcelo de Carvalho Bittencourt⁴  Cécile Pochon⁵  Jean-François Chabot⁶  Simon Valentin⁶  Sébastien Gibot⁷  Antoine Kimmoun⁸  Alice Aarnink⁹  Loic Reppel^1,10  Danièle Bensoussan^1,10  Caroline Laroye^1,10  Véronique Decot^1,10  Mélanie Gauthier^1,10 

[1] CHRU-Nancy, Département Méthodologie, Promotion, Investigation, Hôpitaux de Brabois, Nancy, France;CHRU-Nancy, Département de Pharmacovigilance, Hôpitaux de Brabois, Nancy, France;CHRU-Nancy, HLA and Histocompatibility Laboratory, Nancy, France;CHRU-Nancy, Laboratoire d’immunologie, Hôpitaux de Brabois, Nancy, France;CHRU-Nancy, Pediatric Onco-Hematology Department, Nancy, France;Team 6 IMoPA, UMR 7365 CNRS-UL, Université de Lorraine, Nancy, France;CHRU-Nancy, Pôle des Spécialités Médicales/Département de Pneumologie, Hôpitaux de Brabois, Nancy, France;CHRU-Nancy, Service de Médecine Intensive et Réanimation, Hôpital Central, Nancy, France;CHRU-Nancy, Service de Médecine Intensive et Réanimation, Hôpitaux de Brabois, Nancy, France;Université de Lorraine, Nancy, France;Team 6 IMoPA, UMR 7365 CNRS-UL, Université de Lorraine, Nancy, France;CHRU-Nancy, HLA and Histocompatibility Laboratory, Nancy, France;Team 6 IMoPA, UMR 7365 CNRS-UL, Université de Lorraine, Nancy, France;CHRU-Nancy, Unité de Thérapie Cellulaire et banque de tissus, Nancy, France;

关键词: ARDS;    COVID-19;    mesenchymal stromal cells;    intensive care;    oxygenation;   

DOI  :  10.3389/fmed.2023.1224865

 received in 2023-05-18, accepted in 2023-08-03,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundThe COVID-19 pandemic caused a wave of acute respiratory distress syndrome (ARDS) with a high in-hospital mortality, especially in patients requiring invasive mechanical ventilation. Wharton Jelly-derived Mesenchymal Stromal Cells (WJ-MSCs) may counteract the pulmonary damage induced by the SARS-CoV-2 infection through pro-angiogenic effects, lung epithelial cell protection, and immunomodulation.MethodsIn this randomized, double-blind, placebo-controlled phase 2a trial, adult patients receiving invasive mechanical ventilation for SARS-CoV-2 induced moderate or severe ARDS were assigned to receive 1 intravenous infusion of 1 × 106 WJ-MSCs/kg or placebo within 48 h of invasive ventilation followed by 2 infusions of 0.5 × 106 WJ-MSCs/kg or placebo over 5 days. The primary endpoint was the percentage of patients with a PaO2/FiO2 > 200 on day 10.ResultsThirty patients were included from November 2020 to May 2021, 15 in the WJ-MSC group and 15 in the placebo group. We did not find any significant difference in the PaO2/FiO2 ratio at day 10, with 18 and 15% of WJ-MSCs and placebo-treated patients reaching a ratio >200, respectively. Survival did not differ in the 2 groups with a 20% mortality rate at day 90. While we observed a higher number of ventilation-free days at 28 days in the WJ-MSC arm, this difference was not statistically significant (median of 11 (0–22) vs. 0 (0–18), p = 0.2). The infusions were well tolerated, with a low incidence of anti-HLA alloimmunization after 90 days.ConclusionWhile treatment with WJ-MSCs appeared safe and feasible in patients with SARS-CoV2 moderate or severe ARDS in this phase 2a trial, the treatment was not associated with an increased percentage of patients with P/F > 200 at 10d, nor did 90 day mortality improve in the treated group.Clinical trial registrationhttps://beta.clinicaltrials.gov/study/NCT04625738, identifier NCT04625738.

【 授权许可】

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Copyright © 2023 Pochon, Laroye, Kimmoun, Reppel, Dhuyser, Rousseau, Gauthier, Petitpain, Chabot, Valentin, de Carvalho Bittencourt, Peres, Aarnink, Decot, Bensoussan and Gibot.