In an attempt to modulate mesenchymal stem cells (MSCs) allograft rejection in vivo, the authors transduced MSCs with an interleukin-13 (IL13)-expressing lentiviral vector. Their data clearly indicate that prolonged survival of IL13-expressing allogeneic MSC grafts in muscle tissue coincided with the induction of an alternatively activated macrophage phenotype in vivo and a reduced number of alloantigen-reactive IFNγ- and/or IL2-producing CD8+ T cells compared to nonmodified allografts. Similarly, intracerebral IL13-expressing MSC allografts also exhibited prolonged survival and induction of an alternatively activated macrophage phenotype, although a peripheral T cell component was absent. In summary, this study demonstrates that both innate and adaptive immune responses are effectively modulated in vivo by locally secreted IL13, ultimately resulting in prolonged MSC allograft survival in both muscle and brain tissue.
Here, the authors describe the protocol of ex vivo delivery of growth factors such as GDNF or VEGF via lentiviral vector-mediated genetic modification of human mesenchymal stem cells (hMSCs) and hMSC transplantation into the skeletal muscle of a familial amyotrophic lateral sclerosis rat model.
The authors used a lentiviral vector to express basic fibroblast growth factor (bFGF) in order to investigate the influence of bFGF on osteogenic gene expression. Changes in osteogenic gene expression indicated that the bone marrow stem cells from the experimental group had better osteogenic ability, as compared with the control cells. Therefore, bFGF‑transduced cells may be useful seed cells for bone tissue engineering.
In this study, the authors used lentiviral vectors which express miR-214 or miR-214 sponge to investigate the effect of miR-214 on osteoblast differentiation of mesenchymal stem cells (MSCs)
They find that MiR-214 was up-regulated in MSCs of osteoporotic mice and down-regulated during osteoblast differentiation of MSCs. Furthermore, overexpression of miR-214 inhibited osteoblast differentiation of MSCs in vitro, whereas inhibition of miR-214 function promoted this process, evidenced by increased expression of osteoblast-specific genes, alkaline phosphatase (ALP) activity, and matrix mineralization.
These findings suggest that targeting miR-214 promises to be a potential therapy in treatment of postmenopausal osteoporosis.
In this study, the authors tested the ability of a lentiviral vector (LV) for the in vivo mesenchymal stem cell gene delivery.
They injected a LV expressing GFP into the mice cavity of the femoral bone. After two months, the transferred gene was found in more than 50% of adherent layers of bone marrow cultures formed by mesenchymal stem cells from the infected mice bone marrow. The data confirm the possibility of gene transfer with the lentiviral vectors into the mesenchymal stem cells in vivo.
The authors created genetic engineered mesenchymal stem cell mediating with lentiviral vectors for releasing IL-27 as a good vehicle ex-vivo gene therapy for reduction of inflammation and autoimmune diseases.
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In an attempt to modulate mesenchymal stem cells (MSCs) allograft rejection in vivo, the authors transduced MSCs with an interleukin-13 (IL13)-expressing lentiviral vector. Their data clearly indicate that prolonged survival of IL13-expressing allogeneic MSC grafts in muscle tissue coincided with the induction of an alternatively activated macrophage phenotype in vivo and a reduced number of alloantigen-reactive IFNγ- and/or IL2-producing CD8+ T cells compared to nonmodified allografts. Similarly, intracerebral IL13-expressing MSC allografts also exhibited prolonged survival and induction of an alternatively activated macrophage phenotype, although a peripheral T cell component was absent. In summary, this study demonstrates that both innate and adaptive immune responses are effectively modulated in vivo by locally secreted IL13, ultimately resulting in prolonged MSC allograft survival in both muscle and brain tissue.