(1®6) Glucopiranosil-Glucopiranósidos

2ndMaterials Line Meeting/CQM, January 26th 2007, Funchal, PORTUGAL
Gene Therapy for Bone Regeneration
J.L.Santos1, P.L. Granja2, H. Tomás1
1. Laboratório de Biomateriais e Engenharia de Tecidos, Centro de Química da Madeira,
Departamento de Química da Universidade da Madeira, Campus da Penteada, 9000-390 Funchal,
Portugal.
2. INEB-Instituto de Engenharia Biomédica, Univ. Porto, R. Campo Alegre 823, 4150-180 Porto,
Portugal.
In the past few years gene therapy has captured the scientific and public interest with the promise of
deliver genes and proteins to specific tissues or to replace deficient host cell populations. Genetic
modification is preferred over addition of growth factors since (i) the half-life of growth factors is short,
(ii) a single administration is usually insufficient to produce a biological effect and (iii) usually the
amounts required are very expensive.
In planning gene therapy strategies to promote bone regeneration, both non-viral and viral vectors have
been used to genetically modify cells for factor delivery. Mesenchymal stem cells (MSCs) derived from
bone marrow, muscle, and adipose tissue have been investigated for their ability to retain viability
through the transfection process, for their efficiency at over-expressing growth factors and transcription
factors, and for the quality and quantity of newly formed bone. Due to drawbacks of viral vectors
(immunological response and safety issues) the need to use or develop nonviral vector systems has
been increasingly magnified.
The main objective of our work is to explore the possibility of using cationic polyamidoamine (PAMAM)
dendrimers - nonviral polymeric systems - as vectors for gene delivery into Mesenchymal Stem Cells.
PAMAM dendrimers represent an exciting new class of macromolecular architecture with a high degree
of molecular uniformity, narrow molecular weight distribution, specific size and a well defined shape,
and a highly- functionalized terminal surface, characteristics that become them attractive to gene
delivery.
Hosseinkhani, H., Inatsugu, Y., Hiraoka, Y., Sachiko, I., Shimokawa, H., Tabata, Y., Impregnation of
Plasmid DNA into Three Dimensional Scaffolds and Medium Perfusion Enhance in Vitro DNA
Expression of Mesenchymal Stem Cells. Tissue Eng., 11, 1459, 2005.
Partridge, K. A., and Oreffo, R.O.C., Gene delivery in bone tissue engineering: progress and prospects
using viral and nonviral strategies. Tissue Eng., 10, 295, 2004.
José Luís Santos acknowledges the Portuguese Foundation for Science and Technology (FCT) for the
Ph. D. grant (ref. SFRH/BD/19450/2004).