title: Human embryonic stem cell-derived mesenchymal stroma cells (hES-MSCs) engraft in vivo and support hematopoiesis without suppressing immune function: implications for off-the shelf ES-MSC therapies.
abstract: Mesenchymal stroma cells (MSCs) have a high potential for novel cell therapy approaches in clinical transplantation. Commonly used bone marrow-derived MSCs (BM-MSCs), however, have a restricted proliferative capacity and cultures are difficult to standardize. Recently developed human embryonic stem cell-derived mesenchymal stroma cells (hES-MSCs) might represent an alternative and unlimited source of hMSCs. We therefore compared human ES-cell-derived MSCs (hES-MP002.5 cells) to normal human bone marrow-derived MSCs (BM-MSCs). hES-MP002.5 cells had lower yet reasonable CFU-F capacity compared with BM-MSC (8±3 versus 29±13 CFU-F per 100 cells). Both cell types showed similar immunophenotypic properties, i.e. cells were positive for CD105, CD73, CD166, HLA-ABC, CD44, CD146, CD90, and negative for CD45, CD34, CD14, CD31, CD117, CD19, CD 271, SSEA-4 and HLA-DR. hES-MP002.5 cells, like BM-MSCs, could be differentiated into adipocytes, osteoblasts and chondrocytes in vitro. Neither hES-MP002.5 cells nor BM-MSCs homed to the bone marrow of immune-deficient NSG mice following intravenous transplantation, whereas intra-femoral transplantation into NSG mice resulted in engraftment for both cell types. In vitro long-term culture-initiating cell assays and in vivo co-transplantation experiments with cord blood CD34+ hematopoietic cells demonstrated furthermore that hES-MP002.5 cells, like BM-MSCs, possess potent stroma support function. In contrast to BM-MSCs, however, hES-MP002.5 cells showed no or only little activity in mixed lymphocyte cultures and phytohemagglutinin (PHA) lymphocyte stimulation assays. In summary, ES-cell derived MSCs might be an attractive unlimited source for stroma transplantation approaches without suppressing immune function.
authors: Lund Stem Cell Center, Lund University, Lund, Sweden.
authors: Ou
authors: O
authors: Li
authors: Ariane
authors: A
authors: Tormin
authors: Berit
authors: B
authors: Sundberg
authors: Johan
authors: J
authors: Hyllner
authors: Katarina
authors: K
authors: Le Blanc
authors: Stefan
authors: S
authors: Scheding
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D018929:Cell Culture Techniques; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology*; D005455:Fluorescent Antibody Technique; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods* / Q000639:trends; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D051379:Mice
chemical_list: D016207:Cytokines
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