Mesenchymal stem cell as salvage treatment for refractory chronic GVHD

Abstract

Refractory chronic GVHD (cGVHD) is an important complication after allogeneic hematopoietic SCT and is prognostic of poor outcome. MSCs are involved in tissue repair and modulating immune responses in vitro and in vivo. From April 2005 to October 2008, 19 patients with refractory cGVHD were treated with MSCs derived from the BM of volunteers. The median dose of MSCs was 0.6 × 106 cells per kg body weight. Fourteen of 19 patients (73.7%) responded well to MSCs, achieving a CR (n=4) or a PR (n=10). The immunosuppressive agent could be tapered to less than 50% of the starting dose in 5 of 14 surviving patients, and five patients could discontinue immunosuppressive agents. The median duration between MSC administration and immunosuppressive therapy discontinuation was 324 days (range, 200–550 days). No patients experienced adverse events during or immediately after MSC infusion. The 2-year survival rate was 77.7% in this study. Clinical improvement was accompanied by the increasing ratio of CD5+CD19+/CD5−CD19+ B cells and CD8+CD28−/CD8+CD28+ T cells. In conclusion, transfusion of MSCs expanded in vitro, irrespective of the donor, might be a safe and effective salvage therapy for patients with steroid-resistant, cGVHD.

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

“…These cells are clinically attractive, as they show very low immunogenicity, and they can induce immunosuppression in vitro and in vivo [15], and available data from clinical trials indicate that they are safe and have shown some efficacy in ameliorating GvHD and autoimmune disease outcome in patients [2,[4][5][6][26][27][28][29][30]. However, their mechanism of action is still poorly understood.…”

“…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].…”

Stromal cells–are they really useful for GVHD?

“…In the first patient treated, we saw a partial response. 9 The largest study was from Weng et al 94 who reported on 19 patients with refractory chronic GVHD. These patients were treated with 1-5 doses.…”

Gene Markers Representing Stem Cells and Cancer Cells for Quality Control

“…MSCs are often used for treating graft-versus-host disease (GVHD) (Weng et al, 2010;Le Blanc et al, 2008), suggesting that an infusion of MSCs may be an effective therapy for patients with steroid-resistant acute GVHD. The necdin homologue (mouse) (NDN), EPH receptor A5 (EPHA5), nephroblastoma overexpressed gene (NOV) and runt-related transcription factor 2 (RUNX2) are possible markers to describe culture status, including growth capacity and differentiation (Tanabe et al, 2008).…”