Targeting of mesenchymal stem cells to ovarian tumors via an artificial receptor

doi:10.1186/1757-2215-3-12

Journal of Ovarian Research

Volume 3

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Komarova S
Roth J
Alvarez R
Curiel DT
Pereboeva L

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Roth J
Alvarez R
Curiel DT
Pereboeva L
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Research

Targeting of mesenchymal stem cells to ovarian tumors via an artificial receptor

Svetlana Komarova¹^,2^,3^,4 , Justin Roth¹^,2^,3^,4 , Ronald Alvarez⁵ , David T Curiel¹^,2^,3^,4 and Larisa Pereboeva¹^,2^,3^,4

¹Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294- 2172, USA

²Division of Human Gene Therapy, Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294- 2172, USA

³Division of Human Gene Therapy, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294- 2172, USA

⁴Division of Human Gene Therapy, the Gene Therapy Center, University of Alabama at Birmingham, Birmingham, Alabama 35294- 2172, USA

⁵The Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL 35213, USA

author email corresponding author email

Journal of Ovarian Research 2010, 3:12doi:10.1186/1757-2215-3-12


Published:	25 May 2010

Abstract

Background

Mesenchymal Progenitor/Stem Cells (MSC) respond to homing cues providing an important mechanism to deliver therapeutics to sites of injury and tumors. This property has been confirmed by many investigators, however, the efficiency of tumor homing needs to be improved for effective therapeutic delivery. We investigated the feasibility of enhancing MSC tumor targeting by expressing an artificial tumor-binding receptor on the MSC surface.

Methods

Human MSC expressing an artificial receptor that binds to erbB2, a tumor cell marker, were obtained by transduction with genetically modified adenoviral vectors encoding an artificial receptor (MSC-AR). MSC-AR properties were tested in vitro in cell binding assays and in vivo using two model systems: transient transgenic mice that express human erbB2 in the lungs and ovarian xenograft tumor model. The levels of luciferase-labeled MSCs in erbB2-expressing targeted sites were evaluated by measuring luciferase activity using luciferase assay and imaging.

Results

The expression of AR enhanced binding of MSC-AR to erbB2-expressing cells in vitro, compared to unmodified MSCs. Furthermore, we have tested the properties of erbB2-targeted MSCs in vivo and demonstrated an increased retention of MSC-AR in lungs expressing erbB2. We have also confirmed increased numbers of erbB2-targeted MSCs in ovarian tumors, compared to unmodified MSC. The kinetic of tumor targeting by ip injected MSC was also investigated.

Conclusion

These data demonstrate that targeting abilities of MSCs can be enhanced via introduction of artificial receptors. The application of this strategy for tumor cell-based delivery could increase a number of cell carriers in tumors and enhance efficacy of cell-based therapy.