title: Immunomodulation effects of mesenchymal stromal cells on acute graft-versus-host disease after hematopoietic stem cell transplantation.
abstract: Refractory acute graft-versus-host disease (aGVHD) is a major cause of death after allogeneic hematopoietic stem cell transplantation. This study evaluated the immunomodulation effects of mesenchymal stromal cells (MSCs) from bone marrow of a third-party donor for refractory aGVHD. Forty-seven patients with refractory aGVHD were enrolled: 28 patients receiving MSC and 19 patients without MSC treatment. MSCs were given at a median dose of 1 × 10(6) cells/kg weekly until patients got complete response or received 8 doses of MSCs. After 125 doses of MSCs were administered, with a median of 4 doses (range, 2 to 8) per patient, overall response rate was 75% in the MSC group compared with 42.1% in the non-MSC group (P = .023). The incidence of cytomegalovirus, Epstein-Barr virus infections, and tumor relapse was not different between the 2 groups during aGVHD treatment and follow-up. The incidence and severity of chronic GVHD in the MSC group were lower than those in the non-MSC group (P = .045 and P = .005). The ratio of CD3(+)CD4(+)/CD3(+)CD8(+) T cells, the frequencies of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), and the levels of signal joint T cell-receptor excision DNA circles (sjTRECs) after MSCs treatment were higher than those pretreatment. MSC-treated patients exhibited higher Tregs frequencies and sjTRECs levels than those in the non-MSC group at 8 and 12 weeks after treatment. MSCs derived from bone marrow of a third-party donor are effective to refractory aGVHD. It might reduce the incidence and severity of chronic GVHD in aGVHD patients by improving thymic function and induction of Tregs but not increase the risks of infections and tumor relapse.
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Lou
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Huang
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Hematology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China.
authors.forename: Zujun
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Pediatrics, SUN Yat-Sen Memorial Hospital, SUN Yat-Sen University, Guangzhou, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Huang
authors.affiliation: Institute of Hematology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Can
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Hematology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Institute of Hematology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Yangqiu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xiang
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: liuqifa628@163.com.
authors.forename: Qifa
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D056747:Immunomodulation; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D008875:Middle Aged; D011446:Prospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents
keywords: Graft-versus-host disease; Hematopoietic stem cell transplantation; Immunomodulation; Mesenchymal stromal cell