Brief description of the organization and its infrastructure
The Laboratory of Regenerative Medicine directed by Prof. Cancedda, part of both the Department of Experimental Medicine (DIMES) of the Genova University and the IRCCS AOU San Martino – IST National Institute for Cancer Research, Genova carries out highly specialised activities in the field of Tissue Engineering and Regenerative Medicine in compliance with the regional research and health planning in close connection with national and international research programmes and initiatives.
The Regenerative Medicine laboratory is located in Genova in the Advanced Biotechnology Center Building, within the area of the city/university S. Martino Hospital and extends over 500 square meters. It is fully equipped for experimental work in cell and molecular biology. Equipments and facilities include: Advanced tissue culture and histology facilities, Molecular biology equipments as well as Real time PCR and Microarrays set up, Cell/tissue morphological studies equipments as well as optical, fluorescence and deconvolution microscopes, Animal facilities
Since the mid 80’s culture conditions have been developed in the Laboratory of Regenerative Medicine of the DIMES (directed by prof. R. Cancedda) for the in vitro expansion of human keratinocytes and their employment for in vitro reconstruction of transplantable epithelia (epidermis, urethral mucosa, corneal epithelium). Within this research cultured epithelia have been used for the first time in the world to reconstruct a new urethra in patients affected by severe hypospadias (New England Journal of Medicine, 1990). Furthermore, cultured epithelia allowed the substitution of corneal epithelium in patients with dramatic alkali burns (Lancet, 1994). Since then, the Laboratory has been involved for several years in projects involving mesenchymal progenitors isolated from the marrow stroma on both basic science and applicative aspects. The main research projects carried out have regarded cell biology of the bone marrow stromal cells (differentiation potential, plasticity, senescence), molecular biology of the bone marrow stromal cells (identification of genes expressed by mesenchymal progenitors, identification of genes expressed and regulated during differentiation by mesenchymal progenitors), marrow stroma and its relationship with the hematopoiesis (marrow microenvironment, chemo-radiotherapy toxicity). Subsequently the attention of the Laboratory has moved towards the regeneration and repair of skeletal tissues: i.e. cartilage and bone, with the aid of cells expanded ex vivo derived respectively from a biopsy of articular cartilage and from bone marrow aspirate and the association of different reabsorbable biomaterials. Taking into consideration the experience built with pre-clinical investigations that showed the great applicability of this approach the laboratory began for the first time in the world a clinical trial to reconstruct bone in patients with critical bone segmental defects as a consequence of severe traumas. This research initiated in June 1998 and the results have been published in February 2001 on New England Journal of Medicine. Presently the Laboratory is trying to develop new protocols and procedures that will consider the mesenchymal stem cells derived from bone marrow, adipose or amniotic fluid as “medicinal” cells to reactivate endogenous mechanism of regeneration for the skeletal tissues. Mesenchymal stem cells, or culture medium conditioned by the mesenchymal stem cells, are presented to the damaged tissue associated to suitable scaffolds and in some cases together with platelet derived components.
Previous participation in R&D projects: In the past Unige has been coordinator or partner in several research projects funded by international and national agencies, including EU commission, National and European Space Agencies, Charities such as AIRC and Telethon, Government (University, Health and Industry ministries), University of Pittsburgh, Regione Liguria. In particular in the EU FP6 and FP7 Unige has been or still is partner in the Marie Curie project “JOIN(ed)T”, the Network of Excellence “EXPERTISSUES”, the “Purstem” project, the “Angioscaff” project and the “GAMBA” project.
Research projects presently carried on
The following is an outline of the main research projects presently carried on by the Laboratory:
1) Biology of mesenchymal stem/progenitor cells from bone marrow and other connective tissues including also amniotic fluid (differentiation, plasticity, senescence)
2) Molecular biology of mesenchymal and amniotic fluid derived stem/progenitor cells (identification of genes markers of the early differentiation stages and of genes expressed during cell differentiation)
3) Host response to allogeneic stem cell transplant in immunocompetent animals
4) Tissue engineering for cartilage and bone repair
- a. Active synthetic and natural polymers and co-polymers that can be colonized by chondrogenic cells and implanted. Injectable hydrogels seeded with chondrogenic cells and growth factors.
- b. Ceramic based scaffolds that can be colonized by osteogenic cells and implanted. Resorbable porous
bioceramics. 3D cocoltures of bone depositing and bone resorbing cells
- c. Repair and regeneration of cartilage and bone tissue: small and large animal models.
- d. Structural and biomechanical analysis of engineered tissues.
- e. Cartilage and bone regeneration: new indications for the employment of engineered tissues in phase I and phase II clinical trials.
5) The bone regenerative niche: inflammation, platelet activation, angiogenesis, endogenous cell recruitment
6) Tissue repair/regeneration by a Regenerative Medicine approach. Induction of endogenous regenerative
/repair mechanisms. Role of platelet components. Activation of the process by implantation of stem cells or treatment with stem cell conditioned medium. Adoption of bioactive scaffolds
Ranieri Cancedda, M.D. is a Professor of Cell Biology at the University of Genova, Italy. He also serves as Head of the Laboratory of Regenerative Medicine of the IRCCS AOU San Martino-IST National Cancer Research Institute, Genova. A 1969 magna cum laude graduate of the University of Genova Medical School. Prof. Cancedda went on to complete a postdoctoral training in Nigeria and in the USA. He was Associate Professor of General Biology and Chairman, Department of Cellular and Molecular Biochemistry, 2nd Faculty of Medicine, University of Naples, Italy. In the middle of the 80’s moved to Genova where he has been Professor of General Biology, Dental School, University of Genova and Vice.Scientific Director of the National Cancer Institute from 2001 to 2004. He is Affiliate Member of the Mc Gowan Institute for Regenerative Medicine, Pittsburgh University, USA
Professor Cancedda’s main research fields can be summarized as follows:
- Molecular and cell biology of cartilage and bone
- Tissue engineering and regenerative medicine of skeletal tissue
- Osteobiology in microgravity
Professor Cancedda has spent most of his professional career in studying and developing methods of tissue reconstruction using stem cells, biomaterials and active biomolecules such as growth factors and angiogenic molecules and is considered in academic circles as one of the forefathers of tissue engineering. He has been invited as keynote speaker and lecturer at many international congress and meetings, is the author of more than 270 publications in scientific journals and inventor in 7 patents.