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

Arghya Paul1, Madhur Nayan2, Afshan Afsar Khan1, Dominique Shum-Tim2, Satya Prakash11Biomedical 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 Hos...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Shum-Tim D, Khan AA, Nayan M, Paul A, Prakash S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/ac3a8cc8f3be48abb447ca3836caac0b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ac3a8cc8f3be48abb447ca3836caac0b
record_format	dspace
spelling	oai:doaj.org-article:ac3a8cc8f3be48abb447ca3836caac0b2021-12-02T05:17:41ZAngiopoietin-1-expressing adipose stem cells genetically modified with baculovirus nanocomplex: investigation in rat heart with acute infarction1176-91141178-2013https://doaj.org/article/ac3a8cc8f3be48abb447ca3836caac0b2012-02-01T00:00:00Zhttp://www.dovepress.com/angiopoietin-1-expressing-adipose-stem-cells-genetically-modified-with-a9223https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Arghya Paul1, Madhur Nayan2, Afshan Afsar Khan1, Dominique Shum-Tim2, Satya Prakash11Biomedical 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, CanadaAbstract: 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% &plusmn; 6.3%, P&nbsp;&lt; 0.001 versus control, n = 8) than the hASC group (36.35% &plusmn; 5.7%, P&nbsp;&lt; 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 engineeringShum-Tim DKhan AANayan MPaul APrakash SDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 663-682 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Shum-Tim D Khan AA Nayan M Paul A Prakash S Angiopoietin-1-expressing adipose stem cells genetically modified with baculovirus nanocomplex: investigation in rat heart with acute infarction
description	Arghya Paul1, Madhur Nayan2, Afshan Afsar Khan1, Dominique Shum-Tim2, Satya Prakash11Biomedical 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, CanadaAbstract: 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% &plusmn; 6.3%, P&nbsp;&lt; 0.001 versus control, n = 8) than the hASC group (36.35% &plusmn; 5.7%, P&nbsp;&lt; 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
format	article
author	Shum-Tim D Khan AA Nayan M Paul A Prakash S
author_facet	Shum-Tim D Khan AA Nayan M Paul A Prakash S
author_sort	Shum-Tim D
title	Angiopoietin-1-expressing adipose stem cells genetically modified with baculovirus nanocomplex: investigation in rat heart with acute infarction
title_short	Angiopoietin-1-expressing adipose stem cells genetically modified with baculovirus nanocomplex: investigation in rat heart with acute infarction
title_full	Angiopoietin-1-expressing adipose stem cells genetically modified with baculovirus nanocomplex: investigation in rat heart with acute infarction
title_fullStr	Angiopoietin-1-expressing adipose stem cells genetically modified with baculovirus nanocomplex: investigation in rat heart with acute infarction
title_full_unstemmed	Angiopoietin-1-expressing adipose stem cells genetically modified with baculovirus nanocomplex: investigation in rat heart with acute infarction
title_sort	angiopoietin-1-expressing adipose stem cells genetically modified with baculovirus nanocomplex: investigation in rat heart with acute infarction
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/ac3a8cc8f3be48abb447ca3836caac0b
work_keys_str_mv	AT shumtimd angiopoietin1expressingadiposestemcellsgeneticallymodifiedwithbaculovirusnanocomplexinvestigationinratheartwithacuteinfarction AT khanaa angiopoietin1expressingadiposestemcellsgeneticallymodifiedwithbaculovirusnanocomplexinvestigationinratheartwithacuteinfarction AT nayanm angiopoietin1expressingadiposestemcellsgeneticallymodifiedwithbaculovirusnanocomplexinvestigationinratheartwithacuteinfarction AT paula angiopoietin1expressingadiposestemcellsgeneticallymodifiedwithbaculovirusnanocomplexinvestigationinratheartwithacuteinfarction AT prakashs angiopoietin1expressingadiposestemcellsgeneticallymodifiedwithbaculovirusnanocomplexinvestigationinratheartwithacuteinfarction
_version_	1718400492288081920

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

Ejemplares similares