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Approaches to utilize mesenchymal progenitor cells as cellular vehicles
L Pereboeva1, S Komarova, G Mikheeva
1Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, 35294, USA. larisa.pereboeva@ccc.uab.edu
Stem Cells (Dayton, Ohio)
|July 2, 2003
Summary
Mesenchymal progenitor cells (MPCs) show promise as cellular vectors for cancer therapy. Enhanced adenoviral vectors significantly improved gene delivery into MPCs, enabling them to deliver therapeutic genes or oncolytic viruses to tumors.
Area of Science:
- Gene therapy and cellular vector development
- Oncolytic virotherapy and cancer treatment strategies
Background:
- Mammalian cells offer a novel vector approach for gene delivery, combining cell therapy with gene delivery.
- Mesenchymal progenitor cells (MPCs) possess advantageous properties for use as cellular vehicles in ex vivo gene therapy.
- The ideal cellular vector for ex vivo gene therapy remains to be identified, necessitating evaluation of various cell types.
Purpose of the Study:
- To evaluate the potential utility of mesenchymal progenitor cells (MPCs) as cellular vectors for cancer therapy.
- To enhance the transduction efficiency of MPCs using modified adenoviral vectors.
- To assess the therapeutic potential of gene-modified MPCs in vitro.
Main Methods:
- Transduction of MPCs using conventional adenoviral (Ad) vectors and Ad vectors with incorporated integrin-binding motifs (Ad5lucRGD).
- Evaluation of Ad primary and secondary receptor expression on MPCs.
- Assessment of bystander killing effect of thymidine kinase-expressing MPCs on SKOV3ip1 cancer cells.
- Investigation of Ad replication within MPCs.
Main Results:
- Conventional Ad vectors achieved only 40% transduction efficiency in MPCs due to low primary receptor expression.
- Ad5lucRGD vectors increased MPC transduction efficiency tenfold, enabling efficient genetic loading with reporter and anticancer genes.
- MPCs expressing thymidine kinase demonstrated a bystander killing effect on cancer cells in vitro.
- MPCs supported Ad replication, indicating their potential as vectors for oncolytic viruses.
Conclusions:
- Mesenchymal progenitor cells (MPCs) can be effectively genetically modified using integrin-targeting adenoviral vectors.
- MPCs can serve as cellular vehicles for delivering therapeutic genes (e.g., suicide genes) or oncolytic viruses for cancer treatment.
- MPCs possess key properties for employment as cellular vectors, capable of delivering therapeutic payloads to tumor sites.