Mesenchymal stem cell as salvage treatment for refractory chronic GVHD

J Y Weng, X Du, S X Geng, Y W Peng, Z Wang, Z S Lu, S J Wu, C W Luo, R Guo, W Ling, C X Deng, P J Liao, A P Xiang, J Y Weng, X Du, S X Geng, Y W Peng, Z Wang, Z S Lu, S J Wu, C W Luo, R Guo, W Ling, C X Deng, P J Liao, A P Xiang

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 × 10(6) 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.

Figures

Figure1
Figure1
Characterization and differentiation of human MSCs. (a) Phase-contrast microscopy of human MSCs at passage 3. (b) Alizarin red S staining of osteogenic differentiated human MSCs. (c) Oil red O staining of adipogenic differentiated human MSCs. (d) Toluidine blue staining of chondrogenic differentiated human MSCs. (e) Flow-cytometric analysis of cell surface Ags of human MSCs. Bar=200 μm.

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Source: PubMed

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