One of our main objects is to study possible strategies to enhance tissue regeneration.
We identified in the human adult kidney different populations of resident stem/progenitor cells. In particular we were the first to identify CD133+ progenitor cells in the tubular compartment (Bussolati et al., 2005) and in the medulla (Bussolati B et al., 2011) and a population of mesenchymal stem cells resident in glomeruli (Bruno S et al., 2009).
- to evaluate the role of different sources of stem/progenitor cells (bone marrow, adipose tissue, adult kidney) in different experimental models of acute and chronic renal injury;
- to evaluate the role of bioactive components produced by different stem cells, with particular attention to the extracellular vesicles, in different animal model of acute and chronic renal injury;
- to evaluate the effector shuttled by extracellular vesicles produced by different stem cells, responsible of tissue regeneration effect, with particular attention to the mRNA and microRNA.
We identified in the human liver the presence of a multipotent population of progenitor cells, with characteristic of mesenchymal stem cells, able to contribute to liver regeneration in an experimental model of liver failure (Herrera et al., 2006).
- to evaluate the possibility to utilize this kind of resident stem cells in animal model of fatal liver failure;
- to study the immunomodulatory properties of this stem cell population, in comparison with mesenchymal stem cells from bone marrow;
- to set up GMP conditions to obtain and to expand liver stem cells for possible clinical application.
The extracellular membrane vesicles (EVs) include shedding vesicles, formed by budding of the cell plasma membrane, together with exosomes/microvesicles (MVs) derived from the endosomal membrane compartment by exocytosis. Once released from a given cell type, EVs may interact through specific receptor-ligand with target cells and transfer various bioactive molecules including membrane receptors, proteins, and organelles. The discovery that exosomes and MVs also contain nucleic acids makes them an attractive vehicle for the intercellular trafficking of genetic material.
In our lab, we first found that MVs derived from human endothelial progenitor cells (EPC) contained selected patterns of mRNA that once transferred into quiescent endothelial cells, activate an angiogenic program (Deregibus et al., 2007). We also demonstrated the ability of MVs released from adult stem cells to induce dedifferentiation of cells survived to injury with a cell cycle re-entry and tissue self-repair. This was proved by administration of MVs released from mesenchymal stem cells (MSCs) and liver stem cells (HLSCs) ex vivo in different experimental models of renal and liver injury (Bruno et al., 2009; Gatti et al., 2011; Bruno et al., 2012; Herrera et al., 2010). MVs were found to be able to enter in the renal tubular epithelial cells and in the hepatocytes delivering their genetic content. We also demonstrated that MVs from adult stem cells are enriched of functional microRNAs (Collino et al, 2010). Recently the role of miRNAs shuttled by MVs was enlightened in an experimental model of ischemia-reperfusion injury (IRI) both in vitro and in vivo (Cantaluppi et al., 2012, Collino et al. J Am Soc Nephrol. 2015).
- to evaluate the role of different MVs in renal and liver tissue regeneration in different mice experimental models as well as in angiogenesis.
- to define the role of MVs released by renal cancer stem cells in modifying the tumor microenvironment and support tumor growth.
- acquire information on the mechanisms leading to MV release by adult stem cell.
- to study the genetic content of MV, focusing on their mRNA and miRNA composition and effects on different recipient cells.