Official Sections CTRMS ISVCA IPITA IPTA ISODP IRTA IXA SPLIT TID

2013 - CTS 2013 Congress


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Oral Communications 12

26.3 - MSCs improve refractory chronic GVHD by inducing regulatory CD5+ B lymphocytes

Presenter: Xiaoyong, Chen, Guangzhou, People's Republic of China
Authors: Yanwen Peng1,2,3,4,5,6, Xiaoyong Chen1,2,3,4,5,6, Qifa Liu1,2,3,4,5,6, Ke Huang1,2,3,4,5,6, Longshan Liu1,2,3,4,5,6, Jing Sun1,2,3,4,5,6, Qiuli Liu1,2,3,4,5,6, Andy Peng Xiang1,2,3,4,5,6

MSCs improve refractory chronic GVHD by inducing regulatory CD5+ B lymphocytes

Yanwen Peng1,2,3,4,5,6, Xiaoyong Chen1,2,3,4,5,6, Qifa Liu1,2,3,4,5,6, Ke Huang1,2,3,4,5,6, Longshan Liu1,2,3,4,5,6, Jing Sun1,2,3,4,5,6, Qiuli Liu1,2,3,4,5,6, Andy Peng Xiang1,2,3,4,5,6

1Center for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, People's Republic of China; 2Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou , People's Republic of China; 3Department of Pediatrics, the Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China; 4Laboratory of General Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; 5Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou, People's Republic of China; 6Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China

Background: Refractory chronic graft-versus-host disease(cGVHD) is a significant complication resulting from allogeneic hematopoietic stem cell transplantation. Mesenchymal stromal cells (MSCs) have unique immunomodulatory properties and have shown promising results in the treatment of GVHD.

Method: 23 moderate or severe refractory cGVHD patients that enrolled in study received MSCs treatments as 1×106 cells/kg per infusion and 3 doses at 4-week intervals. Clinical manifestations, laboratory data and peripheral lymphocyte subsets were analyzed pre- and post- MSCs treatment.
Result: In this prospective study, we treated refractorycGVHD patients with MSCs and found that none of the MSCs recipients experienced immediate or long-term toxic side effects. At a 12-month follow-up, 20/23 patients showed complete response (CR) or a partial response (PR),2/23 patients died of fungal pneumonia, and 3 patients died of leukemia relapse.The most dramatic improvements in GVHD symptoms were observed in the skin, oral mucosa, and liver. Clinical improvement was accompanied by an increase in the absolute lymphocyte number;but no significant differences in the frequencies of CD3+ T cells among total lymphocytes, CD4+ T cells among total CD3+ T cells, CD8+ T cells among total CD3+ T cells, or Treg cells among CD4+ T cells were observed between either pre-treatment or post-treatment cGVHD patients and non-GVHD patients.In contrast, MSCs treatment decreased the frequency of B lymphocytes(from 14.92±14.10% to 6.40±4.70%, P<0.01) in the peripheral blood, but significantly increased the frequency of CD5+ regulatory B cells(from 17.60±13.05% to 28.72±20.24% of total B cells, P<0.01). Importantly, CD5+ B cells from cGVHD patients showed increased IL-10 expression after treatment (from 24.90±17.50% to 49.67±22.61% of CD5+B cells, P<0.01), and this was associated with reduced inflammatory cytokine production by T cells, but not  proliferation of T cells. Our data showed thatMSCs perform the immunosuppressive function by enhancing the frequency of CD5+B cells in cGVHD patients through multiple mechanisms, including increasing survival of CD5+ B cells (76.19±8.74% versus 19.94±6.03% without MSCs , P<0.01), promoting proliferation of CD5+ B cells (21.78±3.56% versus 3.91±1.11% without MSCs, P<0.01), and stimulating the production of the anti-inflammatory cytokine IL-10 by CD5+ B cells (9.53±2.91% versus 1.44±0.56% without MSCs, P<0.01). These effects required direct cell-cell interactions and were partially mediated by indoleamine 2, 3-dioxygenase (IDO).
Conclusion: MSCs might exert their immunomodulatory effects on CD5+ regulatory B cells to improve the clinical symptomsof refractory cGVHD. These findings suggest that MSCs represent an effective and novel cell-based therapeutic modality for cGVHD.


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