Clinical Use of Mesenchymal Stromal Cells in the Treatment of Acute Graft-versus-Host Disease

Abstract

Acute graft-versus-host disease (aGvHD) continues to impact morbidity and mortality after allogeneic stem cell transplantation (allo-SCT). First-line therapy for aGvHD still remains the use of high-dose corticosteroids. Unfortunately, 40–60% of patients with aGvHD exhibit steroid resistance, which is associated with a very poor prognosis. As no effective second-line therapy existed, in recent decades various treatment options were considered for the treatment of therapy-refractory GvHD. Based on their in vitro immunomodulatory properties, the use of mesenchymal stromal cells (MSCs) in the treatment of aGvHD has been introduced. However, most of the clinical data are generated from uncontrolled trials and case series, showing clinical responses to MSCs. Clinical results are more consistent in children despite the use of MSC preparations of various provenance and manufacturing protocols. While these data support the therapeutic principle, the great variability of outcomes strongly suggests that not all MSC preparations are equal and that the specific manufacturing protocols influence therapeutic success in vivo.

Mesenchymal stem cell treatment for refractory pediatric rheumatic diseases: A single center case series

“…Studies have shown that providers do not tightly adhere to recommended dosing of GVHD with an average dose of 1.4 × 10 6 MSCs/kg and three total doses administered (range is 1-10 doses administered) [16]. With such varying doses in MSC treatments, adverse events might be expected in the comparatively higher-dosed infusion; but overall, studies have not shown signi cant adverse events, which is consistent with our observations [15][16]. There has been…”

Mesenchymal Stem Cells Beyond Regenerative Medicine

“…The approval emanated from a Phase III trial reporting that Darvadstrocel led to 50% combined remission, which was maintained after 1 year of treatment, in comparison with 34% in the control arm (Panés et al, 2016(Panés et al, , 2018Panes et al, 2017). Interestingly, several "orphan designation" approvals were granted by the European commission according to certain guidelines for the use of human MSCs in the treatment of GvHD, thromboangiitis obliterans (Buerger disease), and ALS (Yu et al, 2018 According to their study, the effectiveness of MSC-FFM is due to donor selection in addition to strict collection and preparation processes (Bader et al, 2018), which yield adequate doses of MSCs with high batch-to-batch consistency (Elgaz et al, 2019). The distinguished data on MSC-FFM clearly elucidate the reasons behind the discrepancies (different survival rates and response levels to allogeneic MSC) and failures of other phase III clinical trials (Galipeau, 2013;Galipeau and Sensébé, 2018).…”

Alternative Immune-Mediated-Based Methods in the Aplastic Anemia Treatment

“…Isolated studies reported serum biomarkers of GVHD severity including IL-2, tumor necrosis factor receptor 1 (TNFR1), regenerating islet-derived protein 3 alpha (Reg3a), and levels of inflammatory cytokines, which not clearly correlate with the response in humans. More studies are needed to obtain correlative research data [94,95]. This outcome results in the first Food and Drug Administration (FDA) approved MSCs product in the United States [96,97].…”