California's Stem Cell Agency
California Institute for regenerative medicine
The State stem cell agency

Lentiviral vectors and protocols for creation of stable hESC lines for fluorescent tracking and drug resistance selection of cardiomyocytes.

Journal: 
PLoS One
Publication Year: 
2009
Authors: 
Hiroko Kita-Matsuo
Maria Barcova
Natalie Prigozhina
Nathan Salomonis
Karen Wei
Jeffrey G Jacot
Brandon Nelson
Sean Spiering
Rene Haverslag
Changsung Kim
Maria Talantova
Ruchi Bajpai
Diego Calzolari
Alexey Terskikh
Andrew D McCulloch
Jeffrey H Price
Bruce R Conklin
H S Vincent Chen
Mark Mercola
PubMed link: 
Read the abstract
Funding Grants: 
Chemical Genetic Approach to Production of hESC-derived Cardiomyocytes
Development of Neuro-Coupled Human Embryonic Stem Cell-Derived Cardiac Pacemaker Cells.
Burnham Institute CIRM Stem Cell Training Grant (Type II)
Public Summary: 
Scientific Abstract: 
BACKGROUND: Developmental, physiological and tissue engineering studies critical to the development of successful myocardial regeneration therapies require new ways to effectively visualize and isolate large numbers of fluorescently labeled, functional cardiomyocytes. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe methods for the clonal expansion of engineered hESCs and make available a suite of lentiviral vectors for that combine Blasticidin, Neomycin and Puromycin resistance based drug selection of pure populations of stem cells and cardiomyocytes with ubiquitous or lineage-specific promoters that direct expression of fluorescent proteins to visualize and track cardiomyocytes and their progenitors. The phospho-glycerate kinase (PGK) promoter was used to ubiquitously direct expression of histone-2B fused eGFP and mCherry proteins to the nucleus to monitor DNA content and enable tracking of cell migration and lineage. Vectors with T/Brachyury and alpha-myosin heavy chain (alphaMHC) promoters targeted fluorescent or drug-resistance proteins to early mesoderm and cardiomyocytes. The drug selection protocol yielded 96% pure cardiomyocytes that could be cultured for over 4 months. Puromycin-selected cardiomyocytes exhibited a gene expression profile similar to that of adult human cardiomyocytes and generated force and action potentials consistent with normal fetal cardiomyocytes, documenting these parameters in hESC-derived cardiomyocytes and validating that the selected cells retained normal differentiation and function. CONCLUSION/SIGNIFICANCE: The protocols, vectors and gene expression data comprise tools to enhance cardiomyocyte production for large-scale applications.