Novel mesenchymal stem cell delivery system as targeted therapy against neuroblastoma using the TH-MYCN mouse model.

PURPOSE:Mesenchymal stem cells (MSCs) are reported to migrate toward damaged tissues or tumors. We previously reported the in vivo short-term (1 day) tumor-homing effect of xenogeneic human MSCs (hMSCs) using the TH-MYCN mouse neuroblastoma model (MYCN-TgM). In this study, we analyzed the long-term tumor-homing effect of allogeneic mouse MSCs (mMSCs) and explored the antitumor effect and drug delivery function of mMSCs. METHODS:mMSCs were administered intraperitoneally (i.p.) to MYCN-TgM and traced by an in vivo imaging system (IVIS). We administered green fluorescent protein (GFP)-transduced mMSCs into MYCN-TgM i.p. and examined the cell survival by immunohistochemistry. We also administered interferon beta-transduced mMSCs (mMSCs-IFN-β) to MYCN-TgM i.p. and measured the concentration of IFN-β in the tumor and organs by an enzyme-linked immunosorbent assay (ELISA). The survival curves of MYCN-TgM administered every week was analyzed. RESULTS:The IVIS revealed the accumulation of fluorescence was observed in the tumor both in vivo and after excision. Immunohistochemistry using anti-GFP antibody revealed that the mMSCs existed within the tumor until 14 days but not in the organs. The ELISA showed increased concentrations of IFN-β only in the tumors, with the values gradually diminishing over 14 days. The mMSCs-IFN-β group survived significantly longer than the control group (p < 0.03), while the mMSCs-alone group did not show a survival advantage. CONCLUSIONS:Allogeneic mMSCs showed a homing ability for mouse neuroblastoma and existed within the tumor for as long as two weeks. This may be a candidate drug delivery vehicle for antitumor agents against neuroblastoma. LEVEL OF EVIDENCE: