Satellite cells are defined by their position beneath the basal lamina of myofibres, and are a source of new myonuclei in adult skeletal muscles. However, other phenotypes also contribute to muscle regeneration, and the relative importance of satellite cells is not known. This work aimed to analyse the stem cell potential of satellite cells by formally investigating their contribution to muscle regeneration. Myofibres isolated from extensor digitorum longus, soleus, and tibialis anterior muscles were found to have respective means of 7,22 and 10 associated satellite cells. When a single myofibre was grafted into an irradiated dystrophic mouse muscle, the associated satellite cells underwent extensive, stem cell-like proliferation, generating progeny which sometimes gave rise to a cluster of more than 100 new myofibres. Cluster size varied according to the muscle group from which the graft was derived, but was not proportional to satellite cell number. Primary myoblasts derived from equivalent muscle groups did not undergo such extensive proliferation, or show inter-muscle variability, suggesting that stem cell activity is critically dependent on a component of the satellite cell niche. Single myofibres isolated from irradiated muscles were non-myogenic after grafting. Satellite cells associated with single myofibres were found to generate new satellite cells in engrafted muscles, demonstrating that satellite cell compartment is maintained by self-renewal. When single myofibre-engrafted muscles were damaged with myotoxin, graft-derived cells underwent rapid clonal expansion to regenerate compact clusters of donor-derived myofibres. The percentage of engrafted muscles containing identifiable donor-derived nuclei was increased after damage, showing that previously inactive cells had been recruited into an active myogenic program. Without experimentally-induced damage, frequency of muscle formation and cluster size were spontaneously augmented over time. These findings demonstrate that satellite cells have several stem cell-like qualities, and thus constitute a self-sufficient and sustainable source of regeneration in adult muscles.

No description available.

No description available.

No description available.

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.

No description available.

No description available.

No description available.

No description available.

No description available.