Adult Human Mesenchymal Stem Cells Added to Corticosteroid Therapy for the Treatment of Acute Graft-versus-Host Disease

Abstract

The unique immunomodulatory properties of mesenchymal stem cells (MSCs) make them a rationale agent to investigate for graft-versus-host disease (GVHD). Human MSCs were used to treat de novo acute GVHD (aGVHD). Patients with grades II-IV GVHD were randomized to receive 2 treatments of human MSCs (Prochymal(R)) at a dose of either 2 or 8 million MSCs/kg in combination with corticosteroids. Patients received GVHD prophylaxis with tacrolimus, cyclosporine, (CsA) or mycophenolate mofetil (MMF). Study endpoints included safety of Prochymal administration, induction of response to Prochymal, and overall response of aGVHD by day 28, and long-term safety. Thirty-two patients were enrolled, with 31 evaluable: 21 males, 10 females; median age 52 years (range: 34-67). Twenty-one patients had grade II, 8 had grade III, and 3 had grade IV aGVHD. Ninety-four percent of patients had an initial response to Prochymal (77% complete response [CR] and 16% partial response [PR]). No infusional toxicities or ectopic tissue formations were reported. There was no difference with respect to safety or efficacy between the low and high Prochymal dose. In conclusion, Prochymal can be infused safely into patients with aGVHD and induces response in a high proportion of GVHD patients.

Stromal cells–are they really useful for GVHD?

“…48 The results are more promising when used at an early stage of GVHD. 86 Bernardo et al 96 treated grade-II acute GVHD with MSCs and reported no deaths that were attributable to acute GVHD as compared with 26% in retrospective control patients. According to animal data, not only early treatment, but also repeated doses may be needed.…”

“…However, this treatment needs to be optimized, combining it with the right immunosuppressive therapies. We need to learn more about the therapeutic potential of stromal cells in order to understand their mechanistic functions Adipose tissue 83,88 Umbilical cord 83,89 Placenta-derived decidua 83,90 Exosomes from stromal cells 76 Expansion media FCS 8,9,[82][83][84][85][86][87] Platelet lysate medium 83,85 AB serum 84 Regulatory T cells CD4 þ in the clinical setting. We have learnt that they are immunosuppressive and that they have regenerative properties, but so far these traits have only been confirmed in vitro.…”

“…Osiris Therapeutics, Inc. used expanded MSCs, Prochymal, for acute GVHD of grades II-IV. 86 Initial response was 94%, with a complete response of 77%.…”

Cord-Blood-Derived Mesenchymal Stromal Cells Downmodulate CD4+T-Cell Activation by Inducing IL-10-Producing Th1 Cells

“…Although the mechanism of action of MSCs is not well understood, they have already entered into clinical trials and, given their low immunogenicity, few if any adverse events have emerged to date [2][3][4][5][6].…”

Human Mesenchymal Stem Cell Therapy for Acute Graft Versus Host Disease

“…The cells are thawed and diluted before administration. Kebriaei et al reported the first randomized, multicenter phase II trial of Prochymal for acute GVHD in 2009 [38]. In the study, Prochymal was administered at two different dose (2 or 8 × 106 cells/kg) with corticosteroid as the first line therapy to the patients with grade II-IV acute GVHD and the overall response rate was 93% (CR, 77%; PR, 16%).…”