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Related Experiment Videos

Human mesenchymal stem cells provide stromal support for efficient CD34+ transduction.

J S Reese1, O N Koç, S L Gerson

  • 1Division of Hematology/Oncology, Case Western Reserve University and University Hospitals, Ireland Cancer Center, Cleveland, OH 44106, USA.

Journal of Hematotherapy & Stem Cell Research
|May 3, 2000
PubMed
Summary

Human mesenchymal stem cells (hMSC) effectively support gene transfer in hematopoietic stem cells, enhancing drug resistance. These cells show promise for clinical gene therapy protocols and broad therapeutic applications.

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Area of Science:

  • Stem cell biology
  • Gene therapy
  • Hematopoiesis

Background:

  • Human mesenchymal stem cells (hMSC) support long-term hematopoiesis.
  • Direct cell contact enhances hematopoietic stem cell engraftment.
  • hMSC offer a homogeneous alternative to heterogeneous stroma in gene transfer.

Purpose of the Study:

  • To evaluate hMSC as support cells for retroviral gene transfer in human hematopoietic progenitors.
  • To assess the ability of hMSC to facilitate gene transfer of the MGMT (deltaMGMT) gene.
  • To determine if transduced cells gain resistance to alkylating agents.

Main Methods:

  • hMSC were used to support retroviral gene transfer of the deltaMGMT gene into human CD34+ cells.
  • Cytokines (IL-3, IL-6, SCF, LIF, Flt-3 ligand) were used to facilitate cell expansion and transduction.

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  • Drug resistance of transduced cells to BCNU and temozolomide (TMZ) was assessed.

    • Main Results:

    • hMSC facilitated expansion and retroviral transduction of CD34+ cells.
    • Transduced hematopoietic cells expressed alkyltransferase (AGT) in 29% of cells.
    • Transduced cells showed a 5-fold increase in resistance to BCNU and TMZ.
    • Simultaneously transduced hMSC expressed AGT in 26% of cells.

    Conclusions:

    • hMSC are effective support cells for retroviral gene transfer in hematopoietic progenitors.
    • hMSC can be transduced themselves, expressing AGT and conferring drug resistance.
    • The homogeneous nature and supportive capabilities of hMSC suggest their utility in clinical gene transfer protocols.