title: Mesenchymal stromal cell supported umbilical cord blood ex vivo expansion enhances regulatory T cells and reduces graft versus host disease.
abstract: OBJECTIVE
  Double cord blood transplantation (DCBT) may shorten neutrophil and platelet recovery times compared with standard umbilical cord blood transplantation. However, DCBT may be associated with a higher incidence of graft versus host disease (GVHD). In this study, we explored the effect of ex vivo expansion of a single cord blood unit (CBU) in a DCBT setting on GVHD and engraftment.
  
  
  METHODS
  Post-thaw cryopreserved CBUs from cord blood banks, hereinafter termed "banked" CBUs, were co-cultured with confluent bone marrow mesenchymal stromal cells (MSCs) supplemented with a cytokine cocktail comprising 100 ng/mL stem cell factor, 50 ng/mL flt3-ligand, 100 ng/mL thrombopoietin and 20 ng/mL insulin-like growth factor binding protein 2 for 12 days.
  
  
  RESULTS
  When DCBT of one unexpanded and one expanded CBU was performed in non-obese diabetic/severe combined immunodeficient-IL2Rgamma(null) (NOD/SCID-IL2γ(-/-), NSG) mice, the expanded CBU significantly boosted in vivo hematopoiesis of the unexpanded CBU. The median survival of NSG mice was significantly improved from 63.4% (range, 60.0-66.7%) for mice receiving only unexpanded units to 86.5% (range, 80.0-92.9%) for mice receiving an expanded unit (P < 0.001). The difference in survival appeared to be due to a lower incidence of GVHD in the mice receiving expanded cells. This effect on GVHD was mediated by a significant increase in regulatory T cells seen in the presence of MSC co-culture.
  
  
  CONCLUSIONS
  MSC-supported ex vivo expansion of "banked" CBU boosted unexpanded CBU hematopoiesis in vivo, increased regulatory T cell content and decreased the incidence of GVHD.
authors: Department of Clinical Research, Singapore General Hospital, Singapore, Singapore.
authors: Xiubo
authors: X
authors: Fan
authors: Florence Pik Hoon
authors: FP
authors: Gay
authors: Shin-Yeu
authors: SY
authors: Ong
authors: Justina May Lynn
authors: JM
authors: Ang
authors: Pat Pak Yan
authors: PP
authors: Chu
authors: Sudipto
authors: S
authors: Bari
authors: Tony Kiat Hon
authors: TK
authors: Lim
authors: William Ying Khee
authors: WY
authors: Hwang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D005312:Fetal Blood / Q000166:cytology / Q000637:transplantation*; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D006410:Hematopoiesis; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D014183:Transplantation, Heterologous