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Journal of Virology, February 2004, p. 1219-1229, Vol. 78, No. 3
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.3.1219-1229.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Transduction of Bone-Marrow-Derived Mesenchymal Stem Cells by Using Lentivirus Vectors Pseudotyped with Modified RD114 Envelope Glycoproteins

Xian-Yang Zhang,¹ Vincent F. La Russa,² and Jakob Reiser^1*

Gene Therapy Program, Department of Medicine, and Department of Microbiology, Immunology and Parasitology, LSU Health Sciences Center,¹ Bone Marrow Transplantation Laboratory, Tulane Cancer Center, New Orleans, Louisiana 70112²

Received 30 May 2003/ Accepted 8 October 2003

Bone-marrow-derived mesenchymal stem cells (MSCs) have attracted considerable attention as tools for the systemic delivery of therapeutic proteins in vivo, and the ability to efficiently transfer genes of interest into such cells would create a number of therapeutic opportunities. We have designed and tested a series of human immunodeficiency virus type 1 (HIV-1)-based vectors and vectors based on the oncogenic murine stem cell virus to deliver and express transgenes in human MSCs. These vectors were pseudotyped with either the vesicular stomatitis virus G (VSV-G) glycoprotein (GP) or the feline endogenous virus RD114 envelope GP. Transduction efficiencies and transgene expression levels in MSCs were analyzed by quantitative flow cytometry and quantitative real-time PCR. While transduction efficiencies with virus particles pseudotyped with the VSV-G GP were found to be high, RD114 pseudotypes revealed transduction efficiencies that were 1 to 2 orders of magnitude below those observed with VSV-G pseudotypes. However, chimeric RD114 GPs, with the transmembrane and extracellular domains fused to the cytoplasmic domain derived from the amphotropic Moloney murine leukemia virus 4070A GP, revealed about 15-fold higher titers relative to the unmodified RD114 GP. The transduction efficiencies in human MSCs of HIV-1-based vectors pseudotyped with the chimeric RD114 GP were similar to those obtained with HIV-1 vectors pseudotyped with the VSV-G GP. Our results also indicate that RD114 pseudotypes were less toxic than VSV-G pseudotypes in human MSC progenitor assays. Taken together, these results suggest that lentivirus pseudotypes bearing alternative Env GPs provide efficient tools for ex vivo modification of human MSCs.

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* Corresponding author. Mailing address: LSU Gene Therapy Program, LSU Health Sciences Center, CSRB 606, 533 Bolivar St., New Orleans, LA 70112. Phone: (504) 568-8005. Fax: (504) 568-8500. E-mail: jreise{at}lsuhsc.edu.

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Journal of Virology, February 2004, p. 1219-1229, Vol. 78, No. 3
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.3.1219-1229.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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