Format

Send to

Choose Destination
See comment in PubMed Commons below
J Vasc Surg. 2008 Feb;47(2):432-40. doi: 10.1016/j.jvs.2007.10.039.

Blood-derived smooth muscle cells as a target for gene delivery.

Author information

1
Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33101, USA.

Abstract

OBJECTIVE:

To examine the feasibility of using blood-derived smooth muscle cells (BD-SMCs) as a target for to deliver therapeutic proteins.

MATERIALS AND METHODS:

Mononuclear cells (MNC) were isolated from peripheral blood. The outgrowth colonies from MNC culture were differentiated into BD-SMCs in media containing platelet-derived growth factor BB. Phenotypic characterization of BD-SMCs was assessed by immunocytochemistry. Cell proliferation, gene transfer efficiency with a retroviral vector, apoptosis, and the biological activity of the transduced gene product from the BD-SMCs were evaluated in vitro and in vivo in comparison with vascular derived SMC (VSMCs).

RESULTS:

BD-SMCs stained positive for SMC markers. No significant difference was observed between BD-SMCs and VSMCs in cell proliferation, migration, adhesiveness, and gene transfer efficiency. After BD-SMCs were transduced with a retroviral vector carrying the secreted alkaline phosphatase gene (SEAP), 174 +/- 50 mug biologically active SEAP was produced per 10(6) cells over 24 hours. After injecting 5 x 10(6) cells expressing SEAP intravenously into rabbits, SEAP concentration increased significantly in the circulation from 0.14 +/- 0.04 mug/ml to 2.34 +/- 0.16 mug/ml 3 days after cell injection (P < .01, n = 3). Circulating levels of SEAP decreased to 1.76 mug /ml 1 week later and remained at this level up to 8 weeks, then declined to pre-cell injection level at 12 weeks. VSMC in vivo gene expression data were equivalent.

CONCLUSION:

BD-SMCs have similar characteristics to mature VSMCs and can be used as a novel target for gene transfer to deliver a therapeutic protein.

PMID:
18241767
PMCID:
PMC2292120
DOI:
10.1016/j.jvs.2007.10.039
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center