title: Plasmid-encapsulated polyethylene glycol-grafted polyethylenimine nanoparticles for gene delivery into rat mesenchymal stem cells.
abstract: BACKGROUND
  Mesenchymal stem cell transplantation is a promising method in regenerative medicine. Gene-modified mesenchymal stem cells possess superior characteristics of specific tissue differentiation, resistance to apoptosis, and directional migration. Viral vectors have the disadvantages of potential immunogenicity, carcinogenicity, and complicated synthetic procedures. Polyethylene glycol-grafted polyethylenimine (PEG-PEI) holds promise in gene delivery because of easy preparation and potentially targeting modification.
  
  
  METHODS
  A PEG8k-PEI25k graft copolymer was synthesized. Agarose gel retardation assay and dynamic light scattering were used to determine the properties of the nanoparticles. MTT reduction, wound and healing, and differentiation assays were used to test the cytobiological characteristics of rat mesenchymal stem cells, fluorescence microscopy and flow cytometry were used to determine transfection efficiency, and atomic force microscopy was used to evaluate the interaction between PEG-PEI/plasmid nanoparticles and mesenchymal stem cells.
  
  
  RESULTS
  After incubation with the copolymer, the bionomics of mesenchymal stem cells showed no significant change. The mesenchymal stem cells still maintained high viability, resettled the wound area, and differentiated into adipocytes and osteoblasts. The PEG-PEI completely packed plasmid and condensed plasmid into stable nanoparticles of 100-150 nm diameter. After optimizing the N/P ratio, the PEG-PEI/plasmid microcapsules delivered plasmid into mesenchymal stem cells and obtained an optimum transfection efficiency of 15%-21%, which was higher than for cationic liposomes.
  
  
  CONCLUSIONS
  These data indicate that PEG-PEI is a valid gene delivery agent and has better transfection efficiency than cationic liposomes in mesenchymal stem cells.
authors: Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors: Xiao-Ai
authors: XA
authors: Chen
authors: Li-Jun
authors: LJ
authors: Zhang
authors: Zhi-Jie
authors: ZJ
authors: He
authors: Wei-Wei
authors: WW
authors: Wang
authors: Bo
authors: B
authors: Xu
authors: Qian
authors: Q
authors: Zhong
authors: Xin-Tao
authors: XT
authors: Shuai
authors: Li-Qun
authors: LQ
authors: Yang
authors: Yu-Bin
authors: YB
authors: Deng
references: Proc Natl Acad Sci U S A. 1995 May 23;92(11):4857-61
references: 7761413
references: Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3908-13
references: 9520466
references: J Virol. 2000 Jun;74(12):5604-18
references: 10823868
references: Mol Ther. 2008 Mar;16(3):571-9
references: 18253156
references: Gene Ther. 2005 Jul;12(14):1119-25
references: 15815702
references: Am J Physiol Heart Circ Physiol. 2007 Mar;292(3):H1278-90
references: 17071732
references: Bioorg Med Chem Lett. 2006 Nov 1;16(21):5572-5
references: 16931009
references: Brain Res. 2008 Feb 21;1195:104-12
references: 18206136
references: Stroke. 2001 Apr;32(4):1005-11
references: 11283404
references: Gene Ther. 2003 Jul;10(13):1089-98
references: 12808439
references: Neurology. 2002 Aug 27;59(4):514-23
references: 12196642
references: Eur J Pharm Biopharm. 2007 Mar;65(3):388-97
references: 17240127
references: Biomaterials. 2008 May;29(15):2415-22
references: 18295879
references: Cytotherapy. 2003;5(6):485-9
references: 14660044
references: Gene Ther. 2000 Jan;7(2):126-38
references: 10673718
references: J Neurol Sci. 2001 Aug 15;189(1-2):49-57
references: 11535233
references: J Biomater Sci Polym Ed. 2010;21(8-9):1103-26
references: 20507711
references: Crit Rev Oral Biol Med. 1999;10(2):165-81
references: 10759420
references: Stem Cells. 2006 Feb;24(2):416-25
references: 16253984
references: J Control Release. 2005 Dec 5;109(1-3):299-316
references: 16298009
references: Bioconjug Chem. 2006 May-Jun;17(3):728-34
references: 16704211
references: Langmuir. 2007 Jan 30;23(3):975-8
references: 17240998
references: Biomaterials. 2007 Feb;28(4):632-40
references: 17049374
references: Int J Nanomedicine. 2010 Mar 09;5:129-36
references: 20309399
references: Biomaterials. 2006 Apr;27(10):2302-12
references: 16337267
references: J Gene Med. 2005 May;7(5):657-63
references: 15543529
references: Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):1972-7
references: 11842191
references: Bioconjug Chem. 2006 Jan-Feb;17(1):125-31
references: 16417260
references: Tissue Eng. 2006 Sep;12(9):2583-90
references: 16995791
references: Int J Pharm. 2006 Aug 31;320(1-2):143-9
references: 16730143
references: Blood. 2005 Feb 15;105(4):1815-22
references: 15494428
references: Tissue Eng. 2006 Jul;12(7):1971-84
references: 16889526
references: Adv Drug Deliv Rev. 2002 Sep 13;54(5):715-58
references: 12204600
references: Mol Cell. 2004 Apr 23;14(2):148-50
references: 15099513
references: Gene Ther. 1999 Apr;6(4):595-605
references: 10476219
references: Cells Tissues Organs. 2010;191(3):185-92
references: 19776549
references: J Biomed Mater Res A. 2006 Sep 15;78(4):702-8
references: 16739172
references: Adv Drug Deliv Rev. 2001 Dec 31;53(3):341-58
references: 11744176
references: J Clin Invest. 1996 Jan 1;97(1):162-71
references: 8550829