title: The role of human umbilical cord tissue-derived mesenchymal stromal cells (UCX®) in the treatment of inflammatory arthritis.
abstract: BACKGROUND
  ECBio has developed proprietary technology to consistently isolate, expand and cryopreserve a well-characterized population of stromal cells from human umbilical cord tissue (UCX® cells). The technology has recently been optimized in order to become compliant with Advanced Medicine Therapeutic Products. In this work we report the immunosuppressive capacity of UCX® cells for treating induced autoimmune inflammatory arthritis.
  
  
  METHODS
  UCX® cells were isolated using a proprietary method (PCT/IB2008/054067) that yields a well-defined number of cells using a precise proportion between tissue digestion enzyme activity units, tissue mass, digestion solution volume and void volume. The procedure includes three recovery steps to avoid non-conformities related to cell recovery. UCX® surface markers were characterized by flow cytometry and UCX® capacity to expand in vitro and to differentiate into adipocyte, chondrocyte and osteoblast-like cells was evaluated. Mixed Lymphocyte Reaction (MLR) assays were performed to evaluate the effect of UCX® cells on T-cell activation and Treg conversion assays were also performed in vitro. Furthermore, UCX® cells were administered in vivo in both a rat acute carrageenan-induced arthritis model and rat chronic adjuvant induced arthritis model for arthritic inflammation. UCX® anti-inflammatory activity was then monitored over time.
  
  
  RESULTS
  UCX® cells stained positive for CD44, CD73, CD90 and CD105; and negative for CD14, CD19 CD31, CD34, CD45 and HLA-DR; and were capable to differentiate into adipocyte, chondrocyte and osteoblast-like cells. UCX® cells were shown to repress T-cell activation and promote the expansion of Tregs better than bone marrow mesenchymal stem cells (BM-MSCs). Accordingly, xenogeneic UCX® administration in an acute carrageenan-induced arthritis model showed that human UCX® cells can reduce paw edema in vivo more efficiently than BM-MSCs. Finally, in a chronic adjuvant induced arthritis model, animals treated with intra-articular (i.a.) and intra-peritoneal (i.p.) infusions of UCX® cells showed faster remission of local and systemic arthritic manifestations.
  
  
  CONCLUSIONS
  The results suggest that UCX® cells may be an effective and promising new approach for treating both local and systemic manifestations of inflammatory arthritis.
authors: ECBio - Investigação e Desenvolvimento em Biotecnologia, Amadora, 2700-451, Portugal. miguel.santos@ecbio.com
authors: Jorge M
authors: JM
authors: Santos
authors: Rita N
authors: RN
authors: Bárcia
authors: Sandra I
authors: SI
authors: Simões
authors: Manuela M
authors: MM
authors: Gaspar
authors: Susana
authors: S
authors: Calado
authors: Ana
authors: A
authors: Agua-Doce
authors: Sílvia C P
authors: SC
authors: Almeida
authors: Joana
authors: J
authors: Almeida
authors: Mariana
authors: M
authors: Filipe
authors: Mariana
authors: M
authors: Teixeira
authors: José P
authors: JP
authors: Martins
authors: Luís
authors: L
authors: Graça
authors: Maria E M
authors: ME
authors: Cruz
authors: Pedro
authors: P
authors: Cruz
authors: Helder
authors: H
authors: Cruz
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D001168:Arthritis / Q000628:therapy*; D001169:Arthritis, Experimental / Q000276:immunology / Q000628:therapy*; D002454:Cell Differentiation; D049109:Cell Proliferation; D005434:Flow Cytometry; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D014470:Umbilical Cord / Q000166:cytology* / Q000276:immunology
chemical_list: D015703:Antigens, CD