In vivo contribution of murine mesenchymal stem cells into multiple cell-types under minimal damage conditions

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Abstract
Murine mesenchymal stem cells are capable of differentiating in vitro into different lineages under stimulation with certain cytokines, growth factors and chemicals. However, the true capacitiy of these cells to contribute to different cell-types in vivo is still unclear, especially under minimal injury conditions. In this study, we describe a method of purifying murine mesenchymal stem cells from bone marrow and efficiently transducing them using a lentivirus vector expressing the eGFP reporter gene. Lentivirus-transduced mesenchymal stem cells retained their in vitro ability to differentiate into adipocytes, osteocytes and chondrocytes as well as into myocyte- and astrocyte-like cells. eGFP-mesenchymal stem cells were delivered systemically into minimally injured syngeneic mice. Tracking and tissue-specific differentiation were determined by PCR and immunohistochemistry, respectively. We found donor-derived hepatocytes, lung epithelial cells, myofibroblasts, myofibers and renal tubular cells in some of the recipient mice. Our data indicate that even in the absence of substantial injury, phenotypically defined murine mesenchymal stem cells could acquire tissue specific morphology and antigen expression and thus contribute to different tissue cell-types in vivo.