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A Novel Strategy to Improve Engraftment of Embryonic Stem Cell‐Derived Cardiomyocytes
Author(s) -
Karabekian Zara,
Gillum Nikki Danielle,
Bakunts Karina,
Wong Elisa,
Sarvazyan Narine
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb93-a
Subject(s) - transfection , embryonic stem cell , microbiology and biotechnology , downregulation and upregulation , progenitor cell , transplantation , stem cell , myocyte , western blot , biology , syncytium , cell culture , medicine , gene , genetics
OBJECTIVE: Studies suggest that transplantation of embryonic stem cells (ESC) following myocardial infarction is beneficial. Since cardiac muscle is a functional syncytium, it is essential to ensure electrical and mechanical engraftment between ESC‐derived cardiac progenitors and host myocardium. Incomplete or functionally impaired grafts exacerbate cardiac tissue heterogeneity, making it highly arrhythmogenic. We hypothesize that overexpression of N‐cadherin will enhance ESC‐derived cardiac progenitor engraftment through upregulation of mechanical and electrical junctions. METHODS: Mouse R1 ESC were transfected with a plasmid containing: N‐cadherin, GFP, and Zeocin resistance genes. Stably transfected ESC were established via Zeocin selection and used to generate embryoid bodies (EB). RESULTS: Immunohistochemistry, qPCR, and western blot analysis confirmed N‐cadherin overexpression in transfected cells. Beating areas of EBs were microdissected and engrafted with neonatal rat cardiomyocytes; engraftment efficiency was assessed using conduction velocity analysis. CONCLUSION: We established a new line of stably transfected ESC with upregulated levels of N‐cadherin. This cell line presents us with a unique in vitro model to study modified adhesion in cardiac engraftment and its possible impact on the substrate arrhythmogenicity. This research was supported by the NIH HL076722 award.