Efficient lentiviral transduction and improved engraftment of human bone marrow mesenchymal cells

An Van Damme, Lieven Thorrez, Ling Ma, Herman Vandenburgh, Jeroen Eyckmans, Francesco Dell'Accio, Cosimo De Bari, Frank Luyten, David Lillicrap, Désiré Collen, Thierry VandenDriessche, Marinee K L Chuah

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Human bone marrow (BM) mesenchymal stem/progenitor cells are potentially attractive targets for ex vivo gene therapy. The potential of lentiviral vectors for transducing BM mesenchymal cells was examined using a self-inactivating vector that expressed the green fluorescent protein (GFP) from an internal cytomegalovirus (CMV) promoter. This vector was compared with oncoretroviral vectors expressing GFP from the CMV promoter or a modified long-terminal repeat that had been optimized for long-term expression in stem cells. The percentage of GFP-positive cells was consistently higher following lentiviral versus oncoretroviral transduction, consistent with increased GFP mRNA levels and increased gene transfer efficiency measured by polymerase chain reaction and Southern blot analysis. In vitro GFP and FVIII expression lasted for several months post-transduction, although expression slowly declined. The transduced cells retained their stem/progenitor cell properties since they were still capable of differentiating along adipogenic and osteogenic lineages in vitro while maintaining high GFP and FVIII expression levels. Implantation of lentivirally transduced human BM mesenchymal cells using collagen scaffolds into immunodeficient mice resulted in efficient engraftment of gene-engineered cells and long-term transgene expression in vivo. These biocompatible BM mesenchymal implants represent a reversible, safe, and versatile protein delivery approach because they can be retrieved in the event of an unexpected adverse reaction or when expression of the protein of interest is no longer required. In conclusion, efficient gene delivery with lentiviral vectors in conjunction with the use of bioengineered reversible scaffolds improves the therapeutic prospects of this novel approach for gene therapy, protein delivery, or tissue engineering.
Original languageEnglish
Pages (from-to)896-907
Number of pages12
JournalStem Cells
Volume24
Issue number4
Early online date9 Dec 2005
DOIs
Publication statusPublished - Apr 2006

Fingerprint

Green Fluorescent Proteins
Bone Marrow Cells
Stem Cells
Cytomegalovirus
Mesenchymal Stromal Cells
Genetic Therapy
Bone Marrow
Genes
Protein Engineering
Proteins
Terminal Repeat Sequences
Tissue Engineering
Southern Blotting
Transgenes
Collagen
Polymerase Chain Reaction
Messenger RNA

Keywords

  • Adipogenesis
  • Base Sequence
  • Biomedical Engineering
  • Cell Differentiation
  • Cells, Cultured
  • DNA
  • Factor VIII
  • Gene Therapy
  • Graft Survival
  • Green Fluorescent Proteins
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells
  • Humans
  • Lentivirus
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells
  • Osteogenesis
  • RNA, Messenger
  • Recombinant Proteins
  • Transduction, Genetic

Cite this

Van Damme, A., Thorrez, L., Ma, L., Vandenburgh, H., Eyckmans, J., Dell'Accio, F., ... Chuah, M. K. L. (2006). Efficient lentiviral transduction and improved engraftment of human bone marrow mesenchymal cells. Stem Cells, 24(4), 896-907. https://doi.org/10.1634/stemcells.2003-0106

Efficient lentiviral transduction and improved engraftment of human bone marrow mesenchymal cells. / Van Damme, An; Thorrez, Lieven; Ma, Ling; Vandenburgh, Herman; Eyckmans, Jeroen; Dell'Accio, Francesco; De Bari, Cosimo; Luyten, Frank; Lillicrap, David; Collen, Désiré; VandenDriessche, Thierry; Chuah, Marinee K L.

In: Stem Cells, Vol. 24, No. 4, 04.2006, p. 896-907.

Research output: Contribution to journalArticle

Van Damme, A, Thorrez, L, Ma, L, Vandenburgh, H, Eyckmans, J, Dell'Accio, F, De Bari, C, Luyten, F, Lillicrap, D, Collen, D, VandenDriessche, T & Chuah, MKL 2006, 'Efficient lentiviral transduction and improved engraftment of human bone marrow mesenchymal cells', Stem Cells, vol. 24, no. 4, pp. 896-907. https://doi.org/10.1634/stemcells.2003-0106
Van Damme A, Thorrez L, Ma L, Vandenburgh H, Eyckmans J, Dell'Accio F et al. Efficient lentiviral transduction and improved engraftment of human bone marrow mesenchymal cells. Stem Cells. 2006 Apr;24(4):896-907. https://doi.org/10.1634/stemcells.2003-0106
Van Damme, An ; Thorrez, Lieven ; Ma, Ling ; Vandenburgh, Herman ; Eyckmans, Jeroen ; Dell'Accio, Francesco ; De Bari, Cosimo ; Luyten, Frank ; Lillicrap, David ; Collen, Désiré ; VandenDriessche, Thierry ; Chuah, Marinee K L. / Efficient lentiviral transduction and improved engraftment of human bone marrow mesenchymal cells. In: Stem Cells. 2006 ; Vol. 24, No. 4. pp. 896-907.
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AU - Thorrez, Lieven

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AU - Dell'Accio, Francesco

AU - De Bari, Cosimo

AU - Luyten, Frank

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KW - Base Sequence

KW - Biomedical Engineering

KW - Cell Differentiation

KW - Cells, Cultured

KW - DNA

KW - Factor VIII

KW - Gene Therapy

KW - Graft Survival

KW - Green Fluorescent Proteins

KW - Hematopoietic Stem Cell Transplantation

KW - Hematopoietic Stem Cells

KW - Humans

KW - Lentivirus

KW - Mesenchymal Stem Cell Transplantation

KW - Mesenchymal Stem Cells

KW - Osteogenesis

KW - RNA, Messenger

KW - Recombinant Proteins

KW - Transduction, Genetic

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DO - 10.1634/stemcells.2003-0106

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JO - Stem Cells

JF - Stem Cells

SN - 1066-5099

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