Targeted gene therapy to antigen-presenting cells in the central nervous system using hematopoietic stem cells

Maciej S. Lesniak, Erin Kelleher, Drew Pardoll, Yan Cui

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Hematopoietic stem cells (HSC) have been previously used as vectors for gene therapy of systemic disease. The effectiveness of HSC-mediated gene therapy largely depends on efficient gene delivery into long-term repopulating progenitors and targeted transgene expression in an appropriate progeny of the transduced pluripotent HSCs. In the present study, we examined the feasibility of using HSC transduced with self-inactivating (SIN) lentiviral vectors for the delivery of gene therapy to the central nervous system (CNS). Material and methods: We constructed two SIN lentiviral vectors, EF.GFP and DR.GFP, to express the green fluorescent protein (GFP) gene controlled solely by the promoter of either a housekeeping gene EF-1α or the human HLA-DRα gene, which is selectively expressed in antigen-presenting cells. Results: We demonstrated that both vectors efficiently transduced human pluripotent CD34+ cells capable of engrafting NOD/SCID mice. Only the DR.GFP vector mediated transgene expression in the murine CNS containing human HLA-DR+ cells. These cells express surface markers characteristic of resident CNS microglia. Furthermore, human dendritic cells derived from transduced and engrafted human cells potently stimulated allogeneic T cell proliferation. Conclusions: The present study demonstrated successful targeting of transgene expression to CNS microglia after stable gene transduction of pluripotent HSC.

Original languageEnglish (US)
Pages (from-to)820-826
Number of pages7
JournalNeurological Research
Volume27
Issue number8
DOIs
StatePublished - Dec 1 2005

Fingerprint

Antigen-Presenting Cells
Hematopoietic Stem Cells
Genetic Therapy
Green Fluorescent Proteins
Central Nervous System
Transgenes
Microglia
HLA-DR Antigens
Genes
Peptide Elongation Factor 1
Pluripotent Stem Cells
Inbred NOD Mouse
SCID Mice
Essential Genes
Dendritic Cells
Cell Proliferation
T-Lymphocytes

Keywords

  • Central nervous system
  • Gene therapy
  • Hematopoietic stem cells
  • Microglia

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Targeted gene therapy to antigen-presenting cells in the central nervous system using hematopoietic stem cells. / Lesniak, Maciej S.; Kelleher, Erin; Pardoll, Drew; Cui, Yan.

In: Neurological Research, Vol. 27, No. 8, 01.12.2005, p. 820-826.

Research output: Contribution to journalArticle

Lesniak, Maciej S. ; Kelleher, Erin ; Pardoll, Drew ; Cui, Yan. / Targeted gene therapy to antigen-presenting cells in the central nervous system using hematopoietic stem cells. In: Neurological Research. 2005 ; Vol. 27, No. 8. pp. 820-826.
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