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Bone marrow stromal cells as a vehicle for gene transfer

Gene Therapy volume 6, pages 1611–1616 (1999)Cite this article

Abstract

Adoptive transfer of genetically modified somatic cells is playing an increasingly important role in the management of a wide spectrum of human diseases. Hematopoietic stem cells and lymphocytes have been used to transfer a variety of genes, however, they have limitations. In this study, the feasibility of retroviral gene transduction of bone marrow stromal cells, and the engraftment characteristics of these cells following infusion, was investigated in a murine transplantation model. Stromal cells derived from Balb/c mouse bone marrow were transduced with a replication-defective retrovirus containing the LacZ gene. Following three rounds of transduction, between 5 and 40% of the cells were positive for the LacZ gene. A total of 2 × 106 cells were infused into the same mouse strain. After the infusion, the LacZ gene was detected by PCR in the bone marrow, spleen, liver, kidney and lung; however, only the spleen and bone marrow samples were strongly positive. Quantitative PCR demonstrated that between 3 and 5% of spleen and bone marrow cells, and 1% of liver cells contained the LacZ gene at 3 weeks after infusion; <0.2% transduced cells were found in other organs. no difference was noted in engraftment between mice with or without irradiation before transplantation, suggesting that engraftment occurred without myeloablation. the infused transduced cells persisted for up to 24 weeks. self-renewal of transplanted stromal cells was demonstrated in secondary transplant studies. ease of culture and gene transduction and tissue specificity to hematopoietic organs (bone marrow, spleen, liver) is demonstrated, indicating that stromal cells may be an ideal vehicle for gene transfer.

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Acknowledgements

This work was supported in part by a grant from American Cancer Society (DHP 153) and USPHS National Heart Blood and Lung Institute (HL-55695) and National Cancer Institute (CA71092) and the Phi Beta Psi Sorority to NCM. We thank the office of grants and Scientific publication at the Arkansas Cancer Research Center (Paula Card-Higginson and Mary Dornhoffer) for assistance with the manuscript.

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Authors and Affiliations

  1. Central Arkansas Veterans Healthcare System, Myeloma and Transplantation Research Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    L Ding, S Lu, R B Batchu & N C Munshi

  2. Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    R L Saylors III

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  1. L Ding
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  2. S Lu
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  3. R B Batchu
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  4. R L Saylors III
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Ding, L., Lu, S., Batchu, R. et al. Bone marrow stromal cells as a vehicle for gene transfer. Gene Ther 6, 1611–1616 (1999). https://doi.org/10.1038/sj.gt.3300973

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