title: Phenotypical and functional characterization of bone marrow mesenchymal stem cells in patients with chronic graft-versus-host disease.
abstract: Chronic graft-versus-host disease (cGVHD) is a critical complication after allogeneic hematopoietic stem cell transplantation. The conditioning therapy has been involved in the impairment of bone marrow (BM) mesenchymal stem/stromal cells (MSCs). However, the potential implication of MSCs in the pathophysiology of cGVHD has not been investigated. We analyzed expanded MSCs from patients with cGVHD and compared them with those from transplantation patients without cGVHD. The MSCs from both groups were of host origin and their reserves were comparable. They showed similar morphology, immunophenotype, population doubling times, self-renewal capacity, differentiation, and migration potential. The immunomodulatory potential of the 2 groups was also identical, they were both capable of inhibiting phytohemagglutinin-activated peripheral blood mononuclear cells (PBMCs) proliferation and inducing regulatory T cells after coculturing with CD4(+) T cells, and the immunosuppressive factors were secreted similarly in both MSCs whether in normal culture or coculture with PBMCs. No significant differences were observed in the cellular senescence and apoptosis between 2 groups. In addition, MSCs from patients with cGVHD displayed normal phenotype and function compared with their counterparts from healthy donors, although reduced frequency in BM mononuclear cell fraction was observed in these patients. Taken together, our results suggest that MSCs do not seem to contribute to the pathogenesis of cGVHD and indicate the feasibility of autologous cell therapy in patients who are not completely responding to standard immunosuppressive therapy for cGVHD.
authors.affiliation: Bone Marrow Transplantation Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Binsheng
authors.initials: B
authors.lastname: Wang
authors.affiliation: Bone Marrow Transplantation Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yongxian
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Bone Marrow Transplantation Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Lizhen
authors.initials: L
authors.lastname: Liu
authors.affiliation: Bone Marrow Transplantation Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Kaimin
authors.initials: K
authors.lastname: Hu
authors.affiliation: Bone Marrow Transplantation Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Ruxiu
authors.initials: R
authors.lastname: Tie
authors.affiliation: Bone Marrow Transplantation Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.affiliation: Bone Marrow Transplantation Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Fu
authors.affiliation: Bone Marrow Transplantation Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Zhu
authors.affiliation: Bone Marrow Transplantation Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Bone Marrow Transplantation Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yu
authors.affiliation: Bone Marrow Transplantation Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: hehuang.zju@gmail.com.
authors.forename: He
authors.initials: H
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D002908:Chronic Disease; D018920:Coculture Techniques; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000473:pathology / Q000628:therapy; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D061251:Primary Cell Culture; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D010835:Phytohemagglutinins
keywords: Bone marrow; Chronic graft-versus-host disease; Hematopoietic stem cell transplantation; Immunomodulation; Mesenchymal stem cells