title: PAMAM dendrimer-baculovirus nanocomplex for microencapsulated adipose stem cell-gene therapy: in vitro and in vivo functional assessment.
abstract: The present study aims to develop a new stem cell based gene delivery system consisting of human adipose tissue derived stem cells (hASCs) genetically modified with self-assembled nanocomplex of recombinant baculovirus and PAMAM dendrimer (Bac-PAMAM) to overexpress the vascular endothelial growth factor (VEGF). Cells were enveloped into branched PEG surface functionalized polymeric microcapsules for efficient transplantation. In vitro analysis confirmed efficient transduction of hASCs expressing 7.65 ± 0.86 ng functionally active VEGF per 10(6) microencapsulated hASCs (ASC-VEGF). To determine the potential of the developed system, chronically infarcted rat hearts were treated with either empty microcapsules (MC), microencapsulated hASCs expressing MGFP reporter protein (MC+ASC-MGFP), or MC+ASC-VEGF, and analyzed for 10 weeks. Post-transplantation data confirmed higher myocardial VEGF expressions with significantly enhanced neovasculature in the MC+ASC-VEGF group. In addition, the cardiac performance, as measured by percentage ejection fraction, also improved significantly in the MC+ASC-VEGF group (48.6 ± 6.1%) compared to that in MC+ASC-MGFP (38.8 ± 5.3%) and MC groups (31.5 ± 3.3%). Collectively, these data demonstrate the feasibility of this system for improved stem cell therapy applications.
authors: Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine, McGill University, 3775 University Street, Montreal, Quebec, H3A 2B4, Canada.
authors: Arghya
authors: A
authors: Paul
authors: Wei
authors: W
authors: Shao
authors: Sana
authors: S
authors: Abbasi
authors: Dominique
authors: D
authors: Shum-Tim
authors: Satya
authors: S
authors: Prakash
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D016367:Baculoviridae / Q000235:genetics* / Q000378:metabolism; D002214:Capsules / Q000008:administration & dosage / Q000737:chemistry; D002478:Cells, Cultured; D050091:Dendrimers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004339:Drug Compounding / Q000379:methods; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009206:Myocardium / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D055672:Static Electricity; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D019076:Transgenes / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics
chemical_list: D002214:Capsules; D050091:Dendrimers; C104700:PAMAM Starburst; D042461:Vascular Endothelial Growth Factor A