[Allogenic transplantation of human mesenchymal stem cells for tissue engineering purposes: an in vitro study].
Due to their plasticity and high proliferation capacity in vitro, human mesenchymal stem cells (MSC) are promising candidates for tissue engineering approaches of mesenchymal tissues like bone, cartilage, or tendon. Undifferentiated MSC do not express immunologically relevant cell surface markers. They inhibit the proliferation of allogeneic T-cells in vitro and elicit no immune response after allogeneic or xenogenic transplantation. Thus, MSC ought to be seen as immunoprivileged or immunomodulating cells. Here, we characterize the immune status and -behavior of MSC and MSC-derived osteogenic precursors in order to evaluate the usefulness of allogeneic MSC for tissue engineering of bone. Human MSC were isolated from bone marrow of hematologically normal voluntary donors. Osteogenic differentiation was induced by adding dexamethasone, ascorbic acid and beta-glycerophosphate. After 0, 8, 16 and 24 days, MSC were co-cultivated with allogeneic mononuclear cells. In parallel, the expression of immunologically relevant cell surface markers was monitored by flow cytometry. Undifferentiated and differentiated MSC did not stimulate allogeneic lymphocytes. MSC were negative for MHC-II, CD40, CD40L, CD80 (B7-1) and CD86 (B7-2), positive for MHC-I, and kept this expression pattern during osteogenic differentiation. Our results support the hypothesis that MSC are immunoprivileged cells which are potentially at disposal for HLA-incompatible cell replacement therapies.
Niemeyer
P
P
Department für Orthopädie und Traumatologie, Klinik für Traumatologie, Universitätsklinikum Freiburg. PhNiemeyer@aol.com
Seckinger
A
A
Simank
H G
HG
Kasten
P
P
Südkamp
N
N
Krause
U
U
D001861:Bone Regeneration / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology*; D008856:Microscopy, Fluorescence; D010006:Osteoblasts / Q000166:cytology* / Q000276:immunology*; D023822:Tissue Engineering / Q000379:methods*; D014184:Transplantation, Homologous