Back to Journals » International Journal of Nanomedicine » Volume 7

Angiopoietin-1-expressing adipose stem cells genetically modified with baculovirus nanocomplex: investigation in rat heart with acute infarction

Authors Paul A, Nayan M, Khan AA, Shum-Tim D, Prakash S

Received 6 October 2011

Accepted for publication 30 October 2011

Published 8 February 2012 Volume 2012:7 Pages 663—682

DOI https://doi.org/10.2147/IJN.S26882

Review by Single-blind

Peer reviewer comments 2

Arghya Paul1, Madhur Nayan2, Afshan Afsar Khan1, Dominique Shum-Tim2, Satya Prakash1
1Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine, McGill University, 2Divisions of Cardiac Surgery and Surgical Research, The Montreal General Hospital, Montreal, QC, Canada

Abstract: The objective of this study was to develop angiopoietin-1 (Ang1)-expressing genetically modified human adipose tissue derived stem cells (hASCs) for myocardial therapy. For this, an efficient gene delivery system using recombinant baculovirus complexed with cell penetrating transactivating transcriptional activator TAT peptide/deoxyribonucleic acid nanoparticles (Bac-NP), through ionic interactions, was used. It was hypothesized that the hybrid Bac-NPAng1 system can efficiently transduce hASCs and induces favorable therapeutic effects when transplanted in vivo. To evaluate this hypothesis, a rat model with acute myocardial infarction and intramyocardially transplanted Ang1-expressing hASCs (hASC-Ang1), genetically modified by Bac-NPAng1, was used. Ang1 is a crucial pro-angiogenic factor for vascular maturation and neovasculogenesis. The released hAng1 from hASC-Ang1 demonstrated profound mitotic and anti-apoptotic activities on endothelial cells and cardiomyocytes. The transplanted hASC-Ang1 group showed higher cell retention compared to hASC and control groups. A significant increase in capillary density and reduction in infarct sizes were noted in the infarcted hearts with hASC-Ang1 treatment compared to infarcted hearts treated with hASC or the untreated group. Furthermore, the hASC-Ang1 group showed significantly higher cardiac performance in echocardiography (ejection fraction 46.28% ± 6.3%, P < 0.001 versus control, n = 8) than the hASC group (36.35% ± 5.7%, P < 0.01, n = 8), 28 days post-infarction. The study identified Bac-NP complex as an advanced gene delivery vehicle for stem cells and demonstrated its potential to treat ischemic heart disease with high therapeutic index for combined stem cell-gene therapy strategy.

Keywords: combined stem cell-gene therapy, baculovirus, nanoparticle, myocardial therapy, angiogenesis, tissue engineering

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Other articles by this author:

Development and characterization of chitosan-PEG-TAT nanoparticles for the intracellular delivery of siRNA

Malhotra M, Tomaro-Duchesneau C, Saha S, Kahouli I, Prakash S

International Journal of Nanomedicine 2013, 8:2041-2052

Published Date: 21 May 2013

Gut microbiota: next frontier in understanding human health and development of biotherapeutics

Prakash S, Rodes L, Coussa-Charley M, Tomaro-Duchesneau C

Biologics: Targets and Therapy 2011, 5:71-86

Published Date: 11 July 2011

Diet-induced metabolic hamster model of nonalcoholic fatty liver disease

Bhathena J, Kulamarva A, Martoni C, Urbanska A, Malhotra M,  Paul A, Prakash S

Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2011, 4:195-203

Published Date: 3 June 2011

A novel method for synthesizing PEGylated chitosan nanoparticles: strategy, preparation, and in vitro analysis

Meenakshi Malhotra, Ciaran Lane, Catherine Tomaro-Duchesneau, et al

International Journal of Nanomedicine 2011, 6:485-494

Published Date: 3 March 2011

Potentials and limitations of microorganisms as renal failure biotherapeutics

Poonam Jain, Sapna Shah, Razek Coussa, Satya Prakash

Biologics: Targets and Therapy 2009, 3:233-243

Published Date: 18 May 2009

Methods, potentials, and limitations of gene delivery to regenerate central nervous system cells

Arvind Kumar, Tryambak D Singh, Santosh K Singh, Satya Prakash

Biologics: Targets and Therapy 2009, 3:245-256

Published Date: 15 May 2009

Colon-targeted delivery of live bacterial cell biotherapeutics including microencapsulated live bacterial cells

Satya Prakash, Aleksandra Malgorzata Urbanska

Biologics: Targets and Therapy 2008, 2:355-378

Published Date: 12 September 2008

Readers of this article also read:

Emerging and future therapies for hemophilia

Carr ME, Tortella BJ

Journal of Blood Medicine 2015, 6:245-255

Published Date: 3 September 2015

Methacrylic-based nanogels for the pH-sensitive delivery of 5-Fluorouracil in the colon

Ashwanikumar N, Kumar NA, Nair SA, Kumar GS

International Journal of Nanomedicine 2012, 7:5769-5779

Published Date: 15 November 2012

Cross-linked acrylic hydrogel for the controlled delivery of hydrophobic drugs in cancer therapy

Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS

International Journal of Nanomedicine 2012, 7:4077-4088

Published Date: 27 July 2012

Crystallization after intravitreal ganciclovir injection

Pitipol Choopong, Nattaporn Tesavibul, Nattawut Rodanant

Clinical Ophthalmology 2010, 4:709-711

Published Date: 14 July 2010