Authors: T.S. Cheung, A. Galleu, M. von Bonin, M. Bornhäuser, F. Dazzi
Published: 2019-06-17
DOI: 10.1097/01.hs9.0000561852.27445.67
Source: Full article
Background:Human mesenchymal stromal cells (MSCs) therapy has demonstrated convincing efficacy in steroid‐resistant acute graft‐versus‐host disease (GvHD). Recently, it has been shown that MSC apoptosis and efferocytosis are essential to mediate MSC therapeutic effects in GvHD. However, there are currently no molecular markers for monitoring this process in patients.Aims:To identify the potential tools for this, we decided to interrogate the molecular and functional profile of human phagocytes exposed to apoptotic MSCs (ApoMSCs) and examined these molecules in GvHD patients.Methods:CD14+ monocytes were isolated from healthy donors’ blood whilst ApoMSCs were generated by treating MSCs with anti‐Fas antibody. Monocytes co‐cultured with ApoMSCs for 8 hours (ApoMSC‐Mono) were characterized using flow cytometry, ELISAs and CD3 T cell proliferation assay. Selective cyclooxygenase2 (COX2) inhibitor NS‐398 was added during the monocyte‐conditioning to assess the role of COX2/prostaglandin E2 (PGE2) in ApoMSC‐Mono. To validate our findings in GvHD patients, sera from 8 severe steroid‐resistant GvHD patients before and after MSC treatment were collected and analyzed. Patients’ clinical responses to MSCs, defined by at least 1 stage reduction in any GvHD organ after infusion, were assessed 1 week after the infusion. To compare the results across patients, we calculated the change in PGE2 levels before and after MSC infusion using the formula [PGE2