Novel Mesenchymal Stem Cell Delivery System as Targeted Therapy Against Neuroblastoma Using the TH-MYCN Mouse Model
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In brief
In brief
This preclinical study demonstrates that allogeneic mouse mesenchymal stem cells home to neuroblastoma tumors and persist for up to 14 days, functioning as targeted drug delivery vehicles. When engineered to express interferon-beta, these MSCs significantly improved survival in the TH-MYCN mouse model, suggesting a promising therapeutic approach for pediatric neuroblastoma.
Written by the GCMD Library team from the article.
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