Design of micro-structured scaffolds for in vitro expansion and differentiation of hematopoietic stem cells in dynamic culture systems


People involved: Monica Soncini, Gianfranco B. Fiore, Alberto Redaelli, Marco Cantini

Funding source: Cariplo Foundation

Grant number: CARIPLO-2006-0687

Funding period: 2007 - 2009

Partners: Laboratory of Biomaterials, Department of Bioengineering, Politecnico di Milano; Institute for Infectious and Tropical Diseases (IMIT), Luigi Sacco Hospital, Milan; Division of Infectious Diseases, San Gerardo Hospital, Monza, Milan.

Aim of the project is to identify and standardize the experimental procedures for the generation of autologous T lymphocytes in vitro through the co-cultivation of of heamatopoietic stem cells (HSC) and thymic stromal cells (TSC) isolated from the same donor. In particular, the research project has two objectives.The first one is to design and manufacture matrices able to reproduce a microenvironment similar to bone marrow compartment (micro-structured matrices optimized for the adhesion and culture of bone marrow stromal cells) aimed at the expansion of HSC through co-cultivation; the goal is to maintain their undifferentiated status thus obtaining an adequate number of cells for possible clinical applications.The second objective is to design and manufacture 3-dimensional scaffolds that can favour the growth of TSC allowing the in vitro regeneration of a tissue similar to the thymus; these substrates will be used for differentiation of HSC towards T lymphocytes reproducing in vitro the same pattern of molecular stimuli that allow T cell differentiation in vivo. Both the generation of cellularized microstructured supports and the co-cultivations aimed at the expansion and at the HSC differentiation towards T lymphocytes, will be carried out in advanced culture systems, optimized for the objectives of the study and endowed with monitoring systems.