Consecutive intrabronchial administration of Wharton's jelly-derived mesenchymal stromal cells in ECMO-supported pediatric patients with end-stage interstitial lung disease: a safety and feasibility study (CIBA method).

Abstract

BACKGROUND: Patients ineligible for lung transplant with end-stage Interstitial Lung Disease (ILD) on Extra-Corporeal Membrane Oxygenation (ECMO) face an appalling prognosis with limited therapeutic options. Due to the beneficial effect of Mesenchymal Stromal Cells (MSC) on inflammatory, immunological and infectious diseases, cell therapy has been proposed as an option, but administration is hampered by the ECMO.

METHODS: Cryopreserved Wharton-jelly derived MSC (WJ-MSC) were conveniently diluted and directly applied consecutively on each lobule (5,1 ml = 10 cells) at a continuous slow rate infused over one hour via flexible bronchoscopy (Consecutive IntraBronchial Administration method, CIBA method).

RESULTS: Intrabronchial administration of MSC to a patient on ECMO was well tolerated by the patient even though it did not reverse the patient's ILD. This manuscript presents preliminary evidence from ongoing clinical trials program on Cell Therapy of Inflammatory, Immune and Infectious Diseases and, to our knowledge, is the first report of intrabronchial administration of MSC in a paediatric ECMO patient with ILD. Even more, MSC administered by this method do not reach the systemic circulation and do get blocked on ECMO membrane.

CONCLUSIONS: Direct intrabronchial administration of MSC in a patient on ECMO is feasible and safe, and may be a new avenue to be assayed in ECMO patients with inflammatory, immunological and infectious diseases of the lung.This method article describes the consecutive intrabronchial administration of cryopreserved Wharton’s jelly-derived mesenchymal stromal cells in an ECMO-supported pediatric patient with end-stage interstitial lung disease. Because intravenous MSC delivery is limited by ECMO circuit retention, obstruction risk and coagulation concerns, the authors developed the CIBA method, consisting of slow lobe-by-lobe intrabronchial infusion via flexible bronchoscopy. The procedure was feasible and well tolerated, although it did not reverse the underlying interstitial lung disease. The work provides a detailed protocol and preliminary safety evidence for local MSC delivery in ECMO-supported pediatric lung disease.