Lentiviral vectors for sustained transgene expression in human bone marrow-derived stromal cells

Xian Yang Zhang, Vincent F. La Russa, Lili Bao, Jay Kolls, Paul Schwarzenberger, Jakob Reiser

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

Bone marrow-derived mesenchymal stromal cells (MSCs) have attracted attention as potential platforms for the systemic delivery of therapeutic proteins in vivo following gene transfer using oncogenic retroviruses. However, the major limitations of this strategy include low levels of gene transfer and a general lack of long-term transgene expression. We have investigated the expression of several transgenes in MSCs following HIV-1 lentiviral vector-mediated gene transfer. Vectors containing a variety of strong promoters driving enhanced green fluorescence protein (EGFP) and coral (Discosoma sp.)-derived red fluorescent protein (DsRed) reporter genes pseudotyped with the vesicular stomatitis virus-G (VSV-G) glycoprotein were able to transduce cultured MSCs with high efficiency. Transduction efficiencies and transgene expression levels in MSCs were found to be higher with lentiviral vectors than with a vector based on the murine stem cell virus pseudotyped with VSV-G. Transgene expression was maintained in culture for at least 5 months. HIV-1-based lentiviral vectors were able to transduce clonogenic mesenchymal progenitor cells, which were capable of maintaining transgene expression by their MSC progeny, over several cell divisions and during differentiation into adipocytes, indicating that terminal adipocyte cell differentiation was unaffected by lentivirus-mediated reporter gene transfer. Collectively these results suggest that lentivirus-mediated gene transfer strategies provide an efficient tool for ex vivo modification of MSCs that does not interfere with differentiation.

Original languageEnglish
Pages (from-to)555-565
Number of pages11
JournalMolecular Therapy
Volume5
Issue number5 I
DOIs
StatePublished - Jun 3 2002

Fingerprint

Mesenchymal Stromal Cells
Transgenes
Lentivirus
Reporter Genes
Adipocytes
Genes
HIV-1
Viruses
Anthozoa
Vesicular Stomatitis
Retroviridae
Cell Division
Cell Differentiation
Glycoproteins
Proteins
Stem Cells
Fluorescence
Bone Marrow

Keywords

  • Gene transfer
  • Lentiviral vectors
  • Long-term expression
  • Mesenchymal stronal cells

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Zhang, X. Y., La Russa, V. F., Bao, L., Kolls, J., Schwarzenberger, P., & Reiser, J. (2002). Lentiviral vectors for sustained transgene expression in human bone marrow-derived stromal cells. Molecular Therapy, 5(5 I), 555-565. https://doi.org/10.1006/mthe.2002.0585

Lentiviral vectors for sustained transgene expression in human bone marrow-derived stromal cells. / Zhang, Xian Yang; La Russa, Vincent F.; Bao, Lili; Kolls, Jay; Schwarzenberger, Paul; Reiser, Jakob.

In: Molecular Therapy, Vol. 5, No. 5 I, 03.06.2002, p. 555-565.

Research output: Contribution to journalArticle

Zhang, XY, La Russa, VF, Bao, L, Kolls, J, Schwarzenberger, P & Reiser, J 2002, 'Lentiviral vectors for sustained transgene expression in human bone marrow-derived stromal cells', Molecular Therapy, vol. 5, no. 5 I, pp. 555-565. https://doi.org/10.1006/mthe.2002.0585
Zhang, Xian Yang ; La Russa, Vincent F. ; Bao, Lili ; Kolls, Jay ; Schwarzenberger, Paul ; Reiser, Jakob. / Lentiviral vectors for sustained transgene expression in human bone marrow-derived stromal cells. In: Molecular Therapy. 2002 ; Vol. 5, No. 5 I. pp. 555-565.
@article{90c3b9e5ffa84b8f97786d94d3a34ab6,
title = "Lentiviral vectors for sustained transgene expression in human bone marrow-derived stromal cells",
abstract = "Bone marrow-derived mesenchymal stromal cells (MSCs) have attracted attention as potential platforms for the systemic delivery of therapeutic proteins in vivo following gene transfer using oncogenic retroviruses. However, the major limitations of this strategy include low levels of gene transfer and a general lack of long-term transgene expression. We have investigated the expression of several transgenes in MSCs following HIV-1 lentiviral vector-mediated gene transfer. Vectors containing a variety of strong promoters driving enhanced green fluorescence protein (EGFP) and coral (Discosoma sp.)-derived red fluorescent protein (DsRed) reporter genes pseudotyped with the vesicular stomatitis virus-G (VSV-G) glycoprotein were able to transduce cultured MSCs with high efficiency. Transduction efficiencies and transgene expression levels in MSCs were found to be higher with lentiviral vectors than with a vector based on the murine stem cell virus pseudotyped with VSV-G. Transgene expression was maintained in culture for at least 5 months. HIV-1-based lentiviral vectors were able to transduce clonogenic mesenchymal progenitor cells, which were capable of maintaining transgene expression by their MSC progeny, over several cell divisions and during differentiation into adipocytes, indicating that terminal adipocyte cell differentiation was unaffected by lentivirus-mediated reporter gene transfer. Collectively these results suggest that lentivirus-mediated gene transfer strategies provide an efficient tool for ex vivo modification of MSCs that does not interfere with differentiation.",
keywords = "Gene transfer, Lentiviral vectors, Long-term expression, Mesenchymal stronal cells",
author = "Zhang, {Xian Yang} and {La Russa}, {Vincent F.} and Lili Bao and Jay Kolls and Paul Schwarzenberger and Jakob Reiser",
year = "2002",
month = "6",
day = "3",
doi = "10.1006/mthe.2002.0585",
language = "English",
volume = "5",
pages = "555--565",
journal = "Molecular Therapy",
issn = "1525-0016",
publisher = "Nature Publishing Group",
number = "5 I",

}

TY - JOUR

T1 - Lentiviral vectors for sustained transgene expression in human bone marrow-derived stromal cells

AU - Zhang, Xian Yang

AU - La Russa, Vincent F.

AU - Bao, Lili

AU - Kolls, Jay

AU - Schwarzenberger, Paul

AU - Reiser, Jakob

PY - 2002/6/3

Y1 - 2002/6/3

N2 - Bone marrow-derived mesenchymal stromal cells (MSCs) have attracted attention as potential platforms for the systemic delivery of therapeutic proteins in vivo following gene transfer using oncogenic retroviruses. However, the major limitations of this strategy include low levels of gene transfer and a general lack of long-term transgene expression. We have investigated the expression of several transgenes in MSCs following HIV-1 lentiviral vector-mediated gene transfer. Vectors containing a variety of strong promoters driving enhanced green fluorescence protein (EGFP) and coral (Discosoma sp.)-derived red fluorescent protein (DsRed) reporter genes pseudotyped with the vesicular stomatitis virus-G (VSV-G) glycoprotein were able to transduce cultured MSCs with high efficiency. Transduction efficiencies and transgene expression levels in MSCs were found to be higher with lentiviral vectors than with a vector based on the murine stem cell virus pseudotyped with VSV-G. Transgene expression was maintained in culture for at least 5 months. HIV-1-based lentiviral vectors were able to transduce clonogenic mesenchymal progenitor cells, which were capable of maintaining transgene expression by their MSC progeny, over several cell divisions and during differentiation into adipocytes, indicating that terminal adipocyte cell differentiation was unaffected by lentivirus-mediated reporter gene transfer. Collectively these results suggest that lentivirus-mediated gene transfer strategies provide an efficient tool for ex vivo modification of MSCs that does not interfere with differentiation.

AB - Bone marrow-derived mesenchymal stromal cells (MSCs) have attracted attention as potential platforms for the systemic delivery of therapeutic proteins in vivo following gene transfer using oncogenic retroviruses. However, the major limitations of this strategy include low levels of gene transfer and a general lack of long-term transgene expression. We have investigated the expression of several transgenes in MSCs following HIV-1 lentiviral vector-mediated gene transfer. Vectors containing a variety of strong promoters driving enhanced green fluorescence protein (EGFP) and coral (Discosoma sp.)-derived red fluorescent protein (DsRed) reporter genes pseudotyped with the vesicular stomatitis virus-G (VSV-G) glycoprotein were able to transduce cultured MSCs with high efficiency. Transduction efficiencies and transgene expression levels in MSCs were found to be higher with lentiviral vectors than with a vector based on the murine stem cell virus pseudotyped with VSV-G. Transgene expression was maintained in culture for at least 5 months. HIV-1-based lentiviral vectors were able to transduce clonogenic mesenchymal progenitor cells, which were capable of maintaining transgene expression by their MSC progeny, over several cell divisions and during differentiation into adipocytes, indicating that terminal adipocyte cell differentiation was unaffected by lentivirus-mediated reporter gene transfer. Collectively these results suggest that lentivirus-mediated gene transfer strategies provide an efficient tool for ex vivo modification of MSCs that does not interfere with differentiation.

KW - Gene transfer

KW - Lentiviral vectors

KW - Long-term expression

KW - Mesenchymal stronal cells

UR - http://www.scopus.com/inward/record.url?scp=0036099109&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036099109&partnerID=8YFLogxK

U2 - 10.1006/mthe.2002.0585

DO - 10.1006/mthe.2002.0585

M3 - Article

VL - 5

SP - 555

EP - 565

JO - Molecular Therapy

JF - Molecular Therapy

SN - 1525-0016

IS - 5 I

ER -