Anti-Angiogenesis Therapy Based on the Bone Marrow- Derived Stromal Cells Genetically Engineered to Express Sflt-1 in Mouse Tumor Model - Genetic Engineering: Recent Developments in Applications - page 208

process of cell proliferation, such as wound and tumor, suggesting that BM-
SCs may be used as a vehicle for gene therapy of tumor.
Methods
Mouse BMSCs were loaded with recombinant adenoviruses which express
soluble Vascular Endothelial Growth Factor Receptor-1 (sFlt-1). The anti-
angiogenesis of sFlt-1 in BMSCs was determined using endothelial cells pro-
liferation inhibition assay and alginate encapsulation assay. The anti-tumor
effects of BMSCs expressing sFlt-1 through tail-vein infusion were evaluated
in two mouse tumor metastases models.
Results
BMSCs genetically modified with Adv-GFP-sFlt-1 could effectively express
and secret sFlt-1. BMSCs loaded with sFlt-1 gene could preferentially home
to tumor loci and decrease lung metastases and prolong lifespan in mouse tu-
mor model through inducing anti-angiogenesis and apoptosis in tumors.
Conclusion
We demonstrated that BMSCs might be employed as a promising vehicle for
tumor gene therapy which can effectively not only improve the concentration
of anticancer therapeutics in tumors, but also modify the tumor microenvi-
ronment.
background
Bone marrow-derived stromal cells (BMSCs), also known as mesenchymal stem
cells or nonhematopoietic progenitor cells, are precursors that can be differenti-
ated into chondrocytes, osteoblasts, adipocytes, neurons and other cell types [1].
They are important for development and cell replenishment of active proliferating
tissues in physiological conditions, such as blood, skin and gut. In pathological
conditions, they are involved in the process of wound healing and tissue regenera-
tion. In animal and clinical experiments, BMSCs have been used for tissue dam-
age repair and functional reconstruction of organs, such as myocardial infarction,
osteogenesis imperfecta, syndrome of multiple organ failure and rebuilding of
hematopoietic system after chemotherapy of breast cancer [2-5].
It has been reported that the conditions featured by enhanced cell proliferation
and tissue remodeling, such as bone fractures, embryo growth and tumorigenesis,
offer an appropriate microenvironment for migration, proliferation and differen-
tiation of stem cells delivered systemically [3,6-9]. The formation of tumor stroma
is similar to that of wound healing and results in a microenvironment which is