The immunologic properties of undifferentiated and osteogenic differentiated mouse mesenchymal stem cells and its potential application in bone regeneration.
The concept of using mesenchymal stem cells (MSCs) in bone repair has progressively evolved, and the goal of cell-mediated therapy is to prolong the natural physiological abilities of healing, or substitute them, when these are lacking, failing, or progressing too slowly. The future application of MSCs in human therapies depends on the establishment of preclinical studies with other mammals, such as mouse. Surprisingly, the immunologic properties of murine MSCs remain poorly documented. In the present study, flow cytometry revealed that undifferentiated murine MSCs and osteogenic cells differentiated from MSCs (DOCs) express major histocompatibility complex (MHC) class I (H-2(b)), but not class II (I-A(b)). After exposure to interferon-gamma (IFN-gamma) for 48h, MHC class II and costimulatory molecules (B7-1 and B7-2) on the cell surface showed evident up-regulation. Undifferentiated MSCs and DOCs proved to be poor stimulators of T cell proliferation, eliciting alloreactive lymphocyte proliferative responses as low-allogenic stimulators. Initial results show that the expression of MHC class I, MHC class II, B7-1 and B7-2 was similar on human bone morphogenetic protein 2 (BMP2)-expressing recombinant adenoviral vector (AdBMP2) transduced MSCs (30 MOI) when compared with non-transduced cells. However, AdBMP2 gene transfected MSCs elicited significant stimulatory responses. The findings will be important for studying the in vivo behaviour and the fate of MSCs after grafting in mouse pathology models in bone regeneration.
Zhang
Xiaoling
X
Institute of Health Sciences and Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 225 South Chongqing Road, Shanghai, PR China.
Tang
Tingting
T
Shi
Qin
Q
Fernandes
Julio C
JC
Dai
Kerong
K
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001861:Bone Regeneration / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D006183:H-2 Antigens / Q000276:immunology; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010012:Osteogenesis / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015533:Transcriptional Activation / Q000276:immunology; D014161:Transduction, Genetic
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D006183:H-2 Antigens; D011994:Recombinant Proteins; D007371:Interferon-gamma