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 217

Verification of BMSCs' Homing to Tumor
It has been reported that ubiquitous tissue distribution of adipose-derived stem
cells in normal mouse was observed when the cells were systematically adminis-
trated [20]. We are concerned about the existence of BMSCs in the metastases and
the surrounding tissues. To detect the tumor tropism of BMSCs after systemically
administration, fluorescent in situ hybridization of Y chromosome was performed
on frozen section of CT26 lung metastasis after BMSCs administration one week.
Positive signals were observed in the frozen section of lung metastases exclusively,
whereas the relatively normal area of lung tissue was totally negative for the fluo-
rescent signals (Figure 6). The tropism of BMSCs to the sites undergoing active
cell growth and differentiation makes them a smart delivery system of therapeutic
agents, especially in gene therapy of cancer and severe destruction of tissues.
Figure 6. Fluorescent in situ hybridization. Frozen sections of lung metastases were tested for the presence of Y
chromosome which is indication of male originated BMSCs by Cy3 labeled Y chromosome probe (STAR*FISH;
Cambio, Cambridge, England). Positive result could be seen in the tumor area obviously, whereas the relatively
normal parts of the sections were totally negative for fluorescent signals.
discussion and conclusion
BMSCs have been used in the therapy of myocardial infarction, osteogenesis im-
perfecta, syndrome of multiple organ failure and rebuilding of haematopoietic
function after chemotherapy of breast cancer in pre-clinical and clinical experi-
ments [2-5]. In this report, we demonstrated that systemically delivered BMSCs
loaded with sFlt-1 gene could preferentially home to tumor loci and induce anti-
angiogenesis as well as apoptosis of cancerous cells, resulting in the decrease of
lung metastases and prolongation of lifespan in mouse tumor model.
The BMSCs' capability of tissue repairing and homing has been attracted great
attention of scientists. Grove reported that up to 20% of lung epithelium could