RGD Reference Report - Local myocardial insulin-like growth factor 1 (IGF-1) delivery with biotinylated peptide nanofibers improves cell therapy for myocardial infarction. - Rat Genome Database

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Local myocardial insulin-like growth factor 1 (IGF-1) delivery with biotinylated peptide nanofibers improves cell therapy for myocardial infarction.

Authors: Davis, ME  Hsieh, PC  Takahashi, T  Song, Q  Zhang, S  Kamm, RD  Grodzinsky, AJ  Anversa, P  Lee, RT 
Citation: Davis ME, etal., Proc Natl Acad Sci U S A. 2006 May 23;103(21):8155-60. Epub 2006 May 12.
RGD ID: 1598426
Pubmed: PMID:16698918   (View Abstract at PubMed)
PMCID: PMC1472445   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0602877103   (Journal Full-text)

Strategies for cardiac repair include injection of cells, but these approaches have been hampered by poor cell engraftment, survival, and differentiation. To address these shortcomings for the purpose of improving cardiac function after injury, we designed self-assembling peptide nanofibers for prolonged delivery of insulin-like growth factor 1 (IGF-1), a cardiomyocyte growth and differentiation factor, to the myocardium, using a "biotin sandwich" approach. Biotinylated IGF-1 was complexed with tetravalent streptavidin and then bound to biotinylated self-assembling peptides. This biotin sandwich strategy allowed binding of IGF-1 but did not prevent self-assembly of the peptides into nanofibers within the myocardium. IGF-1 that was bound to peptide nanofibers activated Akt, decreased activation of caspase-3, and increased expression of cardiac troponin I in cardiomyocytes. After injection into rat myocardium, biotinylated nanofibers provided sustained IGF-1 delivery for 28 days, and targeted delivery of IGF-1 in vivo increased activation of Akt in the myocardium. When combined with transplanted cardiomyocytes, IGF-1 delivery by biotinylated nanofibers decreased caspase-3 cleavage by 28% and increased the myocyte cross-sectional area by 25% compared with cells embedded within nanofibers alone or with untethered IGF-1. Finally, cell therapy with IGF-1 delivery by biotinylated nanofibers improved systolic function after experimental myocardial infarction, demonstrating how engineering the local cellular microenvironment can improve cell therapy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Myocardial Ischemia  ISOIgf1 (Rattus norvegicus)1598426; 1598426 RGD 
Myocardial Ischemia  IDA 1598426 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Igf1  (insulin-like growth factor 1)

Genes (Mus musculus)
Igf1  (insulin-like growth factor 1)

Genes (Homo sapiens)
IGF1  (insulin like growth factor 1)


Additional Information