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Tesi etd-07062011-140720

Thesis type
Tesi di specializzazione
Invadosomi e strutture di membrana sulle Mesodermal Progenitor Cells (MPCs): possibili implicazioni nella somministrazione di cellule multipotenti derivate da midollo osseo.
Corso di studi
relatore Prof. Petrini, Mario
Parole chiave
  • MSC
  • homing
  • MPC
  • CXCR4
  • invadosoma
Data inizio appello
Riassunto analitico
Any promising clinical study concerning the use of MSCs is affected by intrinsic data variability given by the heterogeneity of culture procedures, which often compromise a definitive conclusion and comparison between different studies. Many critical parameters have impact of the composition of the cell preparations as serum supplementation, biomaterials and surface coating, as well as passaging. We recently demonstrated that by substituting human pooled AB serum for fetal bovine serum in culture medium it is possible to isolate bone marrow-derived mesodermal progenitor cell (MPC). MPCs are long-telomere cells expressing pluripotency-associated genes and are able to differentiate in early MSCs and endothelial cells. MPCs are often co-isolated in MSC cultures in different percentage and could represent one of the most influencing causes of results variability between studies on clinical applicability of cultured MSCs. Although, in the last years, many studies reported interesting data on tissue regeneration after local administration of cultured MSCs, systemic delivering of these cells has been the focus of interest in new emerging therapeutical approaches. Controversial data were reported about homing and tissue engraftment ability of systemically administered expanded MSCs and this is probably due to heterogeneity of the cell preparations. However, current studies showed that MSC homing is low and this inefficient process is compromised by entrapment of delivered cells into the lungs or liver.
Here we present convincing data showing that MPC carry the cell surface machinery necessary to migrate toward the injured site or to the bone marrow and then engraft the tissue by trans-endothelial migration, similarly to leukocytes able of diapedesis. On the contrary MSCs don’t exhibit any morpho-funtional structure sustaining extravasation. Consequently, we hypothesize that reported low percentage of engrafted cells, after MSC systemic infusion is the expression of co-cultured MPC while MSCs were passively retained into filter organs as lungs, liver or spleen.