dos Anjos Afonso, F.; (2005) A step towards identifying the true adult murine Mesenchymal Stem Cell. Doctoral thesis , University of London.

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Abstract

Research spanning over a few decades has contributed to the discovery and understanding of a population of cells that are precursors of connective tissue cell-types. These cells currently referred as Mesenchymal Stem Cells (MSCs), have also been shown by some researchers to have the capacity to give rise to neuron- and muscle-like cells in vitro, making them very attractive as cellular source for clinical application in regenerative medicine. Despite the intense focus on therapeutic research on going in the MSC field, the biology of these cells remains elusive, especially at its hierarchical organisation. Although some data suggest that MSCs are composed of different sub-populations of progenitors or cells that are prompted to differentiate preferentially into one or few different cell-types in vitro, there is no defined hierarchy proposed yet, especially at the most primitive level. The initial aim of this project was to characterise the adult murine MSC (muMSCs) compartment since most of the studies performed to date were conducted with human cells. During the process of such, a new cell type was found. Under a conventional isolation/culture system a minor sub-population of muMSCs was identified and then characterised (based on the expression of SSEA-1 antigen Stage Specific Embryonic Antigen-1). The data presented strongly suggest that this new sub-population is not only the founder of the MSC compartment but also they are multipotent both in vitro and in vivo. Moreover, this new cell-type can be directly identified from fresh bone marrow thus confirming its true existence in vivo. Detailed study on SSEA-1 pos-MSCs revealed that these cells present several common features with Embryonic Stem Cells (ES) and therefore suggests that a group of cells with embryonic features might persist throughout adult life. The identification/characterisation of these adult murine SSEA-1pos cells should facilitate the identification of a similar cell-type in the human MSC compartment. Furthermore, this study opens new questions on the developmental origin and importance of adult tissue-specific stem cells in the maintenance of tissue homeostasis.

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