The participation of mesenchymal stem cells in tumor stroma formation and their application as targeted-gene delivery vehicles.
Recent evidence suggests that mesenchymal stem cells (MSC) selectively proliferate to tumors and contribute to the formation of tumor-associated stroma. The biological rationale for tumor recruitment of MSC remains unclear but may represent an effort of the host to blunt tumor cell growth and improve survival. There is mounting experimental evidence that normal stromal cells can revert malignant cell behavior, and separate studies have demonstrated that stromal cells can enhance tumor progression after acquisition of tumor-like genetic lesions. Together, these observations support the rationale for modifying normal MSC to deliver therapeutic proteins directly into the tumor microenvironment. Modified MSC can produce high concentrations of antitumor proteins directly within the Tumor mass, which have been shown to blunt tumor growth kinetics in experimental animal model systems. In this chapter we will address the biological properties of MSC within the tumor microenvironment and discuss the potential use of MSC and other bone marrow-derived cell populations as delivery vehicles for antitumor proteins.
Hall
B
B
Center for Childhood Cancer, Columbus Children's Research Institute, 700 Children's Drive, Columbus, OH 43205, USA.
Andreeff
M
M
Marini
F
F
D000818:Animals; D018450:Disease Progression; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D017154:Stromal Cells / Q000502:physiology*; D014945:Wound Healing