



@article {2240,
	title = {Gene delivery into mesenchymal stem cells: A biomimetic approach using rgd nanoclusters based on poly(amidoamine) dendrimers},
	journal = {BiomacromoleculesBiomacromolecules},
	volume = {12},
	year = {2011},
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},
	month = {2011///},
	pages = {472 - 481},
	abstract = {Poly(amidoamine) dendrimers (generations 5 and 6) with amine termini were conjugated with peptides containing the arginine-glycine-aspartic acid (RGD) sequence having in view their application as gene delivery vectors. The idea behind the work was to take advantage of the cationic nature of dendrimers and of the integrin targeting capabilities of the RGD motif to improve gene delivery. Dendrimers were used as scaffolds for RGD clustering and, by controlling the number of peptides (4, 8, and 16) linked to each dendrimer, it was possible to evaluate the effect of RGD density on the gene delivery process. The new vectors were characterized in respect to their ability to neutralize and compact plasmid DNA (pDNA). The complexes formed by the vectors and pDNA were studied concerning their size, zeta potential, capacity of being internalized by cells and ability of transferring genes. Transfection efficiency was analyzed, first, by using a pDNA encoding for Enhanced Green Fluorescent Protein and Firefly Luciferase and, second, by using a pDNA encoding for Bone Morphogenetic Protein-2. Gene expression in mesenchymal stem cells was enhanced using the new vectors in comparison to native dendrimers and was shown to be dependent on the electrostatic interaction established between the dendrimer moiety and the cell surface, as well as on the RGD density of nanoclusters. The use of dendrimer scaffolds for RGD cluster formation is a new approach that can be extended beyond gene delivery applications, whenever RGD clustering is important for modulating cellular responses. {\textcopyright} 2011 American Chemical Society.},
	keywords = {Amino Acid Sequence, Amino acids, animal cell, animal experiment, Animals, Arginine-glycine-aspartic acids, arginylglycylaspartic acid, article, Biomimetics, bone morphogenetic protein 2, Bone morphogenetic protein-2, Cell culture, Cell membranes, cell surface, Cell surfaces, cell survival, Cellular response, Cluster formations, Complexation, controlled study, dendrimer, Dendrimers, Electrostatic interactions, electrostatic precipitation, Encoding (symbols), Enhanced green fluorescent protein, Firefly luciferase, Functional polymers, Gene delivery, Gene delivery vectors, gene expression, gene targeting, Gene therapy, Gene transfer, Gene Transfer Techniques, gene vector, integrin, Integrins, male, Mesenchymal stem cell, Mesenchymal Stem Cells, Molecular Structure, Nanoclusters, Nanostructures, New approaches, nonhuman, Oligopeptides, Organic acids, Peptides, plasmid DNA, Plasmid DNA (pDNA), polyamidoamine, Polyamidoamine dendrimers, Polyamines, priority journal, rat, Rats, Rats, Wistar, RGD motif, Scaffolds, Stem cells, Structure-Activity Relationship, Targeting capability, Transfection efficiency, Vectors, Zeta potential},
	isbn = {15257797 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-79951658350\&partnerID=40\&md5=a3ef0b57d12de8efb52ba2bf445be126},
	author = {Pandita, D. and Santos, J.L. and Rodrigues, J. and P{\^e}go, A.P. and Granja, P.L. and Tom{\'a}s, H.}
}
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	year = {2011},
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},
	month = {2011///},
	pages = {46 - 57},
	abstract = {Mesenchymal stem cells (MSCs) can be isolated from several tissues in the body, have the ability to selfrenewal, show immune suppressive properties and are multipotent, being able to generate various cell types. At present, due to their intrinsic characteristics, MSCs are considered very promising in the area of tissue engineering and regenerative medicine. In this context, genetic modification can be a powerful tool to control the behavior and fate of these cells and be used in the design of new cellular therapies. Viral systems are very effective in the introduction of exogenous genes inside MSCs. However, the risks associated with their use are leading to an increasing search for non-viral approaches to attain the same purpose, even if MSCs have been shown to be more difficult to transfect in this way. In the past few years, progress was made in the development of chemical and physical methods for non-viral gene delivery. Herein, an overview of the application of those methods specifically to MSCs is given and their use in tissue engineering and regenerative medicine therapeutic strategies highlighted using the example of bone tissue. Key issues and future directions in non-viral gene delivery to MSCs are also critically addressed. {\textcopyright} 2011 Bentham Science Publishers Ltd.},
	keywords = {Animals, article, artificial chromosome, Bone and Bones, Bone Regeneration, bone tissue, Bone tissue engineering, cell based gene therapy, dendrimer, ex vivo gene transfer, Gene delivery, gene targeting, Gene therapy, Gene Transfer Techniques, gene vector, genetic transfection, human, Humans, in vivo gene transfer, liposome, Mesenchymal stem cell, Mesenchymal Stem Cells, nanomedicine, nanoparticle, Non-viral vectors, nonhuman, nonviral gene delivery system, polymer, protein expression, Regeneration, Regenerative Medicine, Tissue engineering, Tissue regeneration},
	isbn = {15665232 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-79951686783\&partnerID=40\&md5=c9cc095fac56b04808553b19fd1f5f48},
	author = {Santos, J.L. and Pandita, D. and Rodrigues, J. and P{\^e}go, A.P. and Granja, P.L. and Tom{\'a}s, H.}
}
@article {2278,
	title = {Functionalization of poly(amidoamine) dendrimers with hydrophobic chains for improved gene delivery in mesenchymal stem cells},
	journal = {Journal of Controlled ReleaseJ. Control. Release},
	volume = {144},
	year = {2010},
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},
	month = {2010///},
	pages = {55 - 64},
	abstract = {A new family of gene delivery vectors is synthesized consisting of a medium-size generation PAMAM dendrimer (generation 5, with amine termini) core randomly linked at the periphery to hydrophobic chains that vary in length (12 to 16 carbon alkyl chains) and number (from 4.2 to 9.7 in average). The idea subjacent to the present work is to join the advantages of the cationic nature of the dendrimer with the capacity of lipids to interact with biological membranes. Unlike other amphiphilic systems designed for the same purpose, where the hydrophobic and hydrophilic moieties coexist in opposite sides, the present vectors have a hydrophilic interior and a hydrophobic corona. The vectors are characterized in respect to their ability to neutralize, bind and compact plasmid DNA (pDNA). The complexes formed between the vectors and pDNA are analyzed concerning their size, ζ-potential, resistance to serum nucleases, capacity of being internalized by cells and transfection efficiency. These new vectors show a remarkable capacity for mediating the internalization of pDNA with minimum cytotoxicity, being this effect positively correlated with the -CH                        2- content present in the hydrophobic corona. Gene expression in MSCs, a cell type with relevancy in the regenerative medicine clinical context, is also enhanced using the new vectors but, in this case, the higher efficiency is shown by the vectors containing the smallest hydrophobic chains. {\textcopyright} 2010 Elsevier B.V.
},
	keywords = {amphophile, animal cell, animal experiment, article, Biological membranes, Biomedical applications, cation, Cations, Cell culture, cell membrane transport, cell type, Cellular uptake, controlled study, Cytotoxicity, dendrimer, Dendrimers, DNA, DNA binding, Dyes, Functional polymers, Gene delivery, gene delivery system, gene expression, Gene therapy, Gene transfer, Gene Transfer Techniques, gene vector, Genes, genetic transfection, Genetic Vectors, Humans, Hydrocarbons, hydrophilicity, hydrophobicity, internalization, lipid, Lipids, male, Mesenchymal stem cell, Mesenchymal Stem Cells, nonhuman, nuclease, Nucleic acids, plasmid DNA, Plasmids, Poly(amidoamine) dendrimers, polyamidoamine, Polyamidoamine dendrimers, priority journal, rat, Regenerative Medicine, Stem cells, Transfection, Vectors, Zeta potential},
	isbn = {01683659 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-77953239685\&partnerID=40\&md5=51dd40fc4a666fd362b5eaa2447703dd},
	author = {Santos, J.L. and Oliveira, H. and Pandita, D. and Rodrigues, J. and P{\^e}go, A.P. and Granja, P.L. and Tom{\'a}s, H.}
}
@article {2272,
	title = {Receptor-mediated gene delivery using PAMAM dendrimers conjugated with peptides recognized by mesenchymal stem cells},
	journal = {Molecular PharmaceuticsMol. Pharm.},
	volume = {7},
	year = {2010},
	note = {Cited By (since 1996): 17Export Date: 21 November 2012Source: Scopusdoi: 10.1021/mp9002877PubMed ID: 20230026Language of Original Document: EnglishCorrespondence Address: Balian, G.; Orthopaedic Research Laboratories, Department of Orthopaedics and Biochemistry and Molecular Genetics, University of Virginia Health System, Charlottesville, VA 22908, United States; email: lenat@uma.ptChemicals/CAS: Dendrimers; Green Fluorescent Proteins, 147336-22-9; PAMAM Starburst; Peptides; enhanced green fluorescent proteinReferences: V{\"a}{\"a}n{\"a}nen, H.K., Mesenchymal stem cells (2005) Ann. Med., 37, pp. 469-479;Caplan, A.I., Adult mesenchymal stem cells for tissue engineering versus regenerative medicine (2007) J. Cell Physiol., 213, pp. 341-347; 
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Hamm, A., Krott, N., Breibach, I., Blindt, R., Bosserhoff, A.K., Efficient transfection method for primary cells (2002) Tissue Eng., 8, pp. 235-245; 
McMahon, J.M., Conroy, S., Lyons, M., Greiser, U., O{\textquoteright}Shea, C., Strappe, P., Howard, L., O{\textquoteright}Brien, T., Gene transfer into rat mesenchymal stem cells: A comparative study of viral and nonviral vectors (2006) Stem Cells Dev., 15, pp. 87-96; 
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},
	month = {2010///},
	pages = {763 - 774},
	abstract = {As mesenchymal stem cells (MSCs) can differentiate into multiple cell types, the delivery of exogenous genes to this type of cell can be an important tool in tissue regeneration and engineering. However transfection of MSCs using nonviral gene delivery vectors is difficult, the development of more efficient and safe DNA vehicles being necessary. Moreover, specific transfection of MSCs may be required to avoid unwanted side effects in other tissues. In this study, a novel family of gene delivery vectors based on poly(amidoamine) (PAMAM) dendrimers functionalized with peptides displaying high affinity toward MSCs was prepared. The vectors were characterized with respect to their ability to neutralize, bind and compact plasmid DNA (pDNA). The complexes formed between the vectors and pDNA were analyzed concerning their size, -potential, capacity of being internalized by cells and transfection efficiency. These new vectors exhibited low cytotoxicity, receptor-mediated gene delivery into MSCs and transfection efficiencies superior to those presented by native dendrimers and by partially degraded dendrimers. {\textcopyright} 2010 American Chemical Society.},
	keywords = {animal cell, animal experiment, animal tissue, Animals, article, asparaginylserylmethionylisoleucylalanylhistidylasparaginyllysylthreonylarginylmethionylhistidylglycylglycylglycylserylcysteine, Cell recognition, cell survival, Cells, Cultured, controlled study, Cytotoxicity, dendrimer, Dendrimers, DNA, DNA binding, Electrophoresis, Agar Gel, flow cytometry, Gene delivery, gene targeting, Gene Transfer Techniques, gene vector, genetic transfection, Genetic Vectors, Green Fluorescent Proteins, male, Mesenchymal stem cell, Mesenchymal Stem Cells, Models, Theoretical, multigene family, nonhuman, PAMAM dendrimers, peptide, Peptides, plasmid DNA, polyamidoamine, priority journal, rat, Rats, Rats, Wistar, serylglycylhistidylglutaminylleucylleucylleucylasparaginyllysylmethionylprolylasparaginylglycylglycylglycylserylcysteine, unclassified drug, Zeta potential},
	isbn = {15438384 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-77953253240\&partnerID=40\&md5=e06048334c689e2faa61e7b6b8ad9bf1},
	author = {Santos, J.L. and Pandita, D. and Rodrigues, J. and P{\^e}go, A.P. and Granja, P.L. and Balian, G. and Tom{\'a}s, H.}
}
