



@article {2313,
	title = {Osteogenic differentiation of mesenchymal stem cells using PAMAM dendrimers as gene delivery vectors},
	journal = {Journal of Controlled ReleaseJ. Control. Release},
	volume = {134},
	year = {2009},
	note = {Cited By (since 1996): 29Export Date: 21 November 2012Source: ScopusCODEN: JCREEdoi: 10.1016/j.jconrel.2008.11.007PubMed ID: 19070635Language of Original Document: EnglishCorrespondence Address: Tom{\'a}s, H.; Centro de Qu{\'\i}mica da Madeira, Departamento de Qu{\'\i}mica, Universidade da Madeira, Campus Universitario da Penteada, 9000-390 Funchal, Portugal; email: lenat@uma.ptChemicals/CAS: alkaline phosphatase, 9001-78-9; calcium, 14092-94-5, 7440-70-2; osteocalcin, 136461-80-8; phosphate, 14066-19-4, 14265-44-2; BMP2 protein, human; Bone Morphogenetic Protein 2; Dendrimers; PAMAM Starburst; Polyamines; beta-Galactosidase, 3.2.1.23References: Dai, J., Rabie, A.B.M., Hagg, U., Xu, R.A., Alternative gene therapy strategies for the repair of craniofacial bone defects (2004) Curr. Gene Ther., 4 (4), pp. 469-485;Gersbach, C.A., Phillips, J.E., Garcia, A.J., Genetic engineering for skeletal regenerative medicine (2007) Annu. Rev. Biomed. Eng., 9, pp. 87-119; 
Kofron, M.D., Laurencin, C.T., Orthopaedic applications of gene therapy (2005) Curr. Gene Ther., 5 (1), pp. 37-61; 
Kofron, M.D., Laurencin, C.T., Bone tissue engineering by gene delivery (2006) Adv. Drug Deliv. Rev., 58 (4), pp. 555-576; 
Luo, J., Sun, M.H., Kang, Q., Peng, Y., Jiang, W., Luu, H.H., Luo, Q., He, T.C., Gene therapy for bone regeneration (2005) Curr. Gene Ther., 5 (2), pp. 167-179; 
Partridge, K.A., Oreffo, R.O., Gene delivery in bone tissue engineering: progress and prospects using viral and nonviral strategies (2004) Tissue Eng., 10 (1-2), pp. 295-307; 
Turgeman, G., Aslan, H., Gazit, Z., Gazit, D., Cell-mediated gene therapy for bone formation and regeneration (2002) Curr. Opin. Mol. Ther., 4 (4), pp. 390-394; 
Chen, Y., Cheung, K.M.C., Kung, H.F., Leong, J.C.Y., Lu, W.W., Luk, K.D.K., In vivo new bone formation by direct transfer of adenoviral-mediated bone morphogenetic protein-4 gene (2002) Biochem. Biophys. Res. Commun., 298 (1), pp. 121-127; 
Lieberman, J.R., Daluiski, A., Stevenson, S., Wu, L., McAllister, P., Lee, Y.P., Kabo, J.M., Witte, O.N., The effect of regional gene therapy with bone morphogenetic protein-2-producing bone-marrow cells on the repair of segmental femoral defects in rats (1999) J. Bone Joint Surg. Am., 81 (7), pp. 905-917; 
Park, J., Ries, J., Gelse, K., Kloss, F., von der Mark, K., Wiltfang, J., Neukam, F.W., Schneider, H., Bone regeneration in critical size defects by cell-mediated BMP-2 gene transfer: a comparison of adenoviral vectors and liposomes (2003) Gene Ther., 10 (13), pp. 1089-1098; 
Riew, K.D., Wright, N.M., Cheng, S.L., Avioli, L.V., Lou, J., Induction of bone formation using a recombinant adenoviral vector carrying the human BMP-2 gene in a rabbit spinal fusion model (1998) Calcif. Tissue Int., 63 (4), pp. 357-360; 
Tsuda, H., Wada, T., Ito, Y., Uchida, H., Dehari, H., Nakamura, K., Sasaki, K., Hamada, H., Efficient BMP2 gene transfer and bone formation of mesenchymal stem cells by a fiber-mutant adenoviral vector (2003) Mol. Ther., 7 (3), pp. 354-365; 
De Laporte, L., Cruz Rea, J., Shea, L.D., Design of modular non-viral gene therapy vectors (2006) Biomaterials, 27 (7), pp. 947-954; 
Eliyahu, H., Barenholz, Y., Domb, A.J., Polymers for DNA delivery (2005) Molecules, 10 (1), pp. 34-64; 
Roth, C.M., Sundaram, S., Engineering synthetic vectors for improved DNA delivery: insights from intracellular pathways (2004) Annu. Rev. Biomed. Eng., 6, pp. 397-426; 
Corsi, K., Chellat, F., Yahia, L., Fernandes, J.C., Mesenchymal stem cells, MG63 and HEK293 transfection using chitosan-DNA nanoparticles (2003) Biomaterials, 24 (7), pp. 1255-1264; 
Hamm, A., Krott, N., Breibach, I., Blindt, R., Bosserhoff, A.K., Efficient transfection method for primary cells (2002) Tissue Eng., 8 (2), pp. 235-245; 
Lakshmipathy, U., Pelacho, B., Sudo, K., Linehan, J.L., Coucouvanis, E., Kaufman, D.S., Verfaillie, C.M., Efficient transfection of embryonic and adult stem cells (2004) Stem Cells, 22 (4), pp. 531-543; 
Kim, S.W., Ogawa, T., Tabata, Y., Nishimura, I., Efficacy and cytotoxicity of cationic-agent-mediated nonviral gene transfer into osteoblasts (2004) J. Biomed. Mater. Res. A, 71 (2), pp. 308-315; 
Dufes, C., Uchegbu, I.F., Schatzlein, A.G., Dendrimers in gene delivery (2005) Adv. Drug Deliv. Rev., 57 (15), pp. 2177-2202; 
Guillot-Nieckowski, M., Eisler, S., Diederich, F., Dendritic vectors for gene transfection (2007) New J. Chem., 31 (7), pp. 1111-1127; 
Svenson, S., Tomalia, D.A., Dendrimers in biomedical applications-reflections on the field (2005) Adv. Drug Deliv. Rev., 57 (15), pp. 2106-2129; 
Haensler, J., Szoka, F.C., Polyamidoamine cascade polymers mediate efficient transfection of cells in culture (1993) Bioconjug. Chem., 4 (5), pp. 372-379; 
Choi, J.S., Nam, K., Park, J., Kim, J.B., Lee, J.K., Park, J., Enhanced transfection efficiency of PAMAM dendrimer by surface modification with l-arginine (2004) J. Control. Release, 99 (3), pp. 445-456; 
Kono, K., Akiyama, H., Takahashi, T., Takagishi, T., Harada, A., Transfection activity of polyamidoamine dendrimers having hydrophobic amino acid residues in the periphery (2005) Bioconjug. Chem., 16 (1), pp. 208-214; 
KukowskaLatallo, J.F., Bielinska, A.U., Johnson, J., Spindler, R., Tomalia, D.A., Baker, J.R., Efficient transfer of genetic material into mammalian cells using Starburst polyamidoamine dendrimers (1996) Proc. Natl. Acad. Sci. U. S. A., 93 (10), pp. 4897-4902; 
Gebhart, C.L., Kabanov, A.V., Evaluation of polyplexes as gene transfer agents (2001) J. Control. Release, 73 (2), pp. 401-416; 
Aubin, J.E., Osteoprogenitor cell frequency in rat bone marrow stromal populations: role for heterotypic cell-cell interactions in osteoblast differentiation (1999) J. Cell. Biochem., 72 (3), pp. 396-410; 
Lennon, D.P., Haynesworth, S.E., Young, R.G., Dennis, J.E., Caplan, A.I., A chemically-defined medium supports in-vitro proliferation and maintains the osteochondral potential of rat marrow-derived mesenchymal stem-cells (1995) Exp. Cell Res., 219 (1), pp. 211-222; 
Bielinska, A.U., Chen, C.L., Johnson, J., Baker, J.R., DNA complexing with polyamidoamine dendrimers: implications for transfection (1999) Bioconjug. Chem., 10 (5), pp. 843-850; 
Eichman, J.D., Bielinska, A.U., Kukowska-Latallo, J.F., Baker Jr., J.R., The use of PAMAM dendrimers in the efficient transfer of genetic material into cells (2000) Pharm. Sci. Technol. Today, 7, pp. 232-245; 
Haleem-Smith, H., Derfoul, A., Okafor, C., Tuli, R., Olsen, D., Hall, D.J., Tuan, R.S., Optimization of high-efficiency transfection of adult human mesenchymal stem cells in vitro (2005) Mol. Biotechnol., 30 (1), pp. 9-19; 
Fischer, D., Li, Y.X., Ahlemeyer, B., Krieglstein, J., Kissel, T., In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis (2003) Biomaterials, 24 (7), pp. 1121-1131; 
Jevprasesphant, R., Penny, J., Jalal, R., Attwood, D., McKeown, N.B., D{\textquoteright}Emanuele, A., The influence of surface modification on the cytotoxicity of PAMAM dendrimers (2003) Int. J. Pharm., 252 (1-2), pp. 263-266; 
Wilke, M., Fortunati, E., vandenBroek, M., Hoogeveen, A.T., Scholte, B.J., Efficacy of a peptide-based gene delivery system depends on mitotic activity (1996) Gene Ther., 3 (12), pp. 1133-1142; 
Xie, Y.B., Yang, S.T., Kniss, D.A., Three-dimensional cell-scaffold constructs promote efficient gene transfection: implications for cell-based gene therapy (2001) Tissue Eng., 7 (5), pp. 585-598; 
Yamagiwa, H., Endo, N., Tokunaga, K., Hayami, T., Hatano, H., Takahashi, H.E., In vivo bone-forming capacity of human bone marrow-derived stromal cells is stimulated by recombinant human bone morphogenetic protein-2 (2001) J. Bone Miner. Metab., 19 (1), pp. 20-28; 
Chaudhari, A., Ron, E., Rethman, M.P., Recombinant human bone morphogenetic protein-2 stimulates differentiation in primary cultures of fetal rat calvarial osteoblasts (1997) Mol. Cell. Biochem., 167 (1-2), pp. 31-39; 
Hay, E., Hott, M., Graulet, A.M., Lomri, A., Marie, P.J., Effects of bone morphogenetic protein-2 on human neonatal calvaria cell differentiation (1999) J. Cell. Biochem., 72 (1), pp. 81-93; 
Yamaguchi, A., Regulation of differentiation pathway of skeletal mesenchymal cells in cell-lines by transforming growth-factor-beta superfamily (1995) Semin. Cell Biol., 6 (3), pp. 165-173; 
Yamaguchi, A., Ishizuya, T., Kintou, N., Wada, Y., Katagiri, T., Wozney, J.M., Rosen, V., Yoshiki, S., Effects of BMP-2, BMP-4, and BMP-6 on osteoblastic differentiation of bone marrow-derived stromal cell lines, ST2 and MC3T3-G2/PA6 (1996) Biochem. Biophys. Res. Commun., 220 (2), pp. 366-371; 
Baltzer, A.W.A., Lattermann, C., Whalen, J.D., Wooley, P., Weiss, K., Grimm, M., Ghivizzani, S.C., Evans, C.H., Genetic enhancement of fracture repair: healing of an experimental segmental defect by adenoviral transfer of the BMP-2 gene (2000) Gene Ther., 7 (9), pp. 734-739; 
Wang, E.A., Rosen, V., Dalessandro, J.S., Bauduy, M., Cordes, P., Harada, T., Israel, D.I., Wozney, J.M., Recombinant human bone morphogenetic protein induces bone-formation (1990) Proc. Natl. Acad. Sci. U. S. A., 87 (6), pp. 2220-2224; 
Chuang, C.K., Sung, L.Y., Hwang, S.M., Lo, W.H., Chen, H.C., Hu, Y.C., Baculovirus as a new gene delivery vector for stem cell engineering and bone tissue engineering (2007) Gene Ther., 14 (19), pp. 1417-1424; 
Aslan, H., Zilberman, Y., Arbeli, V., Sheyn, D., Matan, Y., Liebergall, M., Li, J.Z., Gazit, Z., Nucleofection-based ex vivo nonviral gene delivery to human stem cells as a platform for tissue regeneration (2006) Tissue Eng., 12 (4), pp. 877-889; 
Noel, D., Gazit, D., Bouquet, C., Apparailly, F., Bony, C., Plence, P., Millet, V., Jorgensen, C., Short-term BMP-2 expression is sufficient for in vivo osteochondral differentiation of mesenchymal stem cells (2003) Stem Cells, 22 (1), pp. 74-85
},
	month = {2009///},
	pages = {141 - 148},
	abstract = {This paper reports the use of different generations of polyamidoamine (PAMAM) dendrimers for the in vitro transfection of mesenchymal stem cells (MSCs). A systematic study was carried out on the transfection efficiency achieved by the PAMAM dendrimers using a β-galactosidase reporter gene system. Transfection results were shown to be dependent upon the generation of dendrimers, the amine to phosphate group ratio and the cell passage number. In all cases, the transfection efficiency was very low. Nevertheless, it was hypothesized that a low transfection level could be sufficient to promote the in vitro differentiation of MSCs towards the osteoblastic lineage. To address this possibility, dendrimers carrying the human bone morphogenetic protein-2 (hBMP-2) gene-containing plasmid were used. All quantitative (alkaline phosphatase activity, osteocalcin secretion and calcium deposition) and qualitative (von Kossa staining) osteogenic markers were significantly stronger in transfected cells when compared to non-transfected ones. This study not only clearly demonstrates that a low transfection level can be sufficient for inducing in vitro differentiation of MSCs to the osteoblast phenotype but also highlights the importance of focusing research on the development of gene delivery vectors in the concrete application. {\textcopyright} 2008 Elsevier B.V. All rights reserved.},
	keywords = {alkaline phosphatase, amine, Amines, animal cell, Animals, article, beta galactosidase, beta-Galactosidase, Bone, Bone morphogenetic protein, bone morphogenetic protein 2, Bone Regeneration, Calcium, Cell culture, cell differentiation, Cell Line, cell lineage, cell survival, Cells, Cells, Cultured, controlled study, dendrimer, Dendrimers, embryo, enzyme activity, Flowcharting, gene expression, Gene transfer, Gene Transfer Techniques, gene vector, Genes, Reporter, genetic transfection, human, human cell, Humans, in vitro study, Kidney, male, Mesenchymal stem cell, Mesenchymal Stem Cells, nonhuman, Nonviral gene delivery, nonviral gene delivery system, Nucleic acids, osteoblast, osteocalcin, Osteogenesis, PAMAM dendrimers, phosphate, plasmid, Plasmids, polyamidoamine, Polyamines, priority journal, protein secretion, Proteins, qualitative analysis, quantitative analysis, rat, Rats, Rats, Wistar, reporter gene, staining},
	isbn = {01683659 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-60649096454\&partnerID=40\&md5=90df49394a581738b41bf29bad341ae8},
	author = {Santos, J.L. and Oramas, E. and P{\^e}go, A.P. and Granja, P.L. and Tom{\'a}s, H.}
}
