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

Svetlana Komarova1, Justin Roth, Ronald Alvarez

  • 1Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294- 2172, USA. lpereb@uab.edu.

Abstract

Insights

Engineered Mesenchymal Stem Cells (MSCs) with artificial receptors show enhanced tumor targeting. This improved homing increases the number of therapeutic cell carriers in tumors, boosting cell-based therapy efficacy.

Area of Science:

  • Biomedical Engineering
  • Cell Biology
  • Cancer Therapeutics

Background:

  • Mesenchymal Stem Cells (MSCs) are utilized for targeted therapeutic delivery to injury sites and tumors.
  • Current MSC tumor homing efficiency requires improvement for effective cancer treatment.
  • This study explores enhancing MSC tumor targeting by engineering artificial receptors onto their surface.

Purpose of the Study:

  • To investigate the feasibility of enhancing Mesenchymal Stem Cell (MSC) tumor targeting through the expression of artificial tumor-binding receptors.
  • To evaluate the in vitro and in vivo efficacy of engineered MSCs with enhanced tumor-homing capabilities.

Main Methods:

  • Human MSCs were genetically modified using adenoviral vectors to express an artificial receptor (MSC-AR) targeting the tumor marker erbB2.
  • In vitro cell binding assays and in vivo studies using erbB2-expressing transgenic mice and ovarian xenograft models were performed.
  • Luciferase-labeled MSCs were quantified in targeted sites using luciferase assays and imaging to assess homing efficiency.

Main Results:

  • Engineered MSC-AR demonstrated significantly enhanced binding to erbB2-expressing cells in vitro compared to unmodified MSCs.
  • In vivo studies showed increased retention of MSC-AR in erbB2-expressing lungs and a higher number of MSC-AR within ovarian tumors.
  • The kinetics of tumor targeting following intraperitoneal injection of MSCs were also analyzed.

Conclusions:

  • Introducing artificial receptors enhances the tumor-targeting abilities of Mesenchymal Stem Cells (MSCs).
  • This strategy holds potential for improving cell-based cancer therapy by increasing the number of therapeutic cell carriers within tumors.
  • Engineered MSCs represent a promising approach for more effective targeted cancer treatment.