title: VEGF therapeutic gene delivery using dendrimer type bio-reducible polymer into human mesenchymal stem cells (hMSCs).
abstract: The therapeutic potential of mesenchymal stem cells (MSCs) has garnered great attention in the expansive diversity of biomedical research. Despite this broad interest in stem cells, limited incorporation and poor viability are major disadvantages for accomplishing therapeutic success in the field of hMSC-based cell therapy, and an optimal approach for hMSC-based cell therapy using non-viral vectors has not been established. Hence, we examined the possibility of performing gene therapy using the biodegradable polymeric non-viral vector Arginine-grafted poly (cystaminebisacrylamide-diaminohexane) (ABP)-conjugated poly (amidoamine) (PAMAM) dendrimer (PAM-ABP) in hMSCs. PAM-ABP formed compact nanosized polyplexes and showed low cytotoxicity compared to bPEI 25k and Lipofectamine® 2000 in hMSCs. Although the cellular uptake was similar, the transfection efficiency and VEGF expression of PAM-ABP using gWiz-Luc and pβ-VEGF were higher than those of the control groups. Although hMSCs were transfected, their stem cell characteristics were retained. Our results suggest that PAM-ABP has the ability to deliver a therapeutic gene in hMSCs.
authors.affiliation: Pharmicell Co., Ltd., Sungnam, Republic of Korea.
authors.forename: Hyojung
authors.initials: H
authors.lastname: Kim
authors.affiliation: Center for Controlled Chemical Delivery (CCCD), Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, USA.
authors.forename: Kihoon
authors.initials: K
authors.lastname: Nam
authors.affiliation: Center for Controlled Chemical Delivery (CCCD), Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, USA.
authors.forename: Joung-Pyo
authors.initials: JP
authors.lastname: Nam
authors.affiliation: Pharmicell Co., Ltd., Sungnam, Republic of Korea.
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Pharmicell Co., Ltd., Sungnam, Republic of Korea.
authors.forename: Yong Man
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Pharmicell Co., Ltd., Sungnam, Republic of Korea.
authors.forename: Wan Seok
authors.initials: WS
authors.lastname: Joo
authors.affiliation: Center for Controlled Chemical Delivery (CCCD), Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, USA. Electronic address: SW.Kim@pharm.utah.edu.
authors.forename: Sung Wan
authors.initials: SW
authors.lastname: Kim
mesh_terms: D002478:Cells, Cultured; D050091:Dendrimers / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008055:Lipids / Q000633:toxicity; D049409:Luciferases, Firefly / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008875:Middle Aged; D053758:Nanoparticles; D010641:Phenotype; D011094:Polyethyleneimine / Q000378:metabolism / Q000633:toxicity; D014162:Transfection / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D050091:Dendrimers; D008055:Lipids; C086724:Lipofectamine; C000611299:PAM-ABP dendrimer; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D011094:Polyethyleneimine; D049409:Luciferases, Firefly
keywords: Bio-reducible polymer; Mesenchymal stem cell; Non-viral vector; Therapeutic gene; VEGF