Monitoring the Bystander Killing Effect of Human Multipotent Stem Cells for Treatment of Malignant Brain Tumors

Stem Cells International
Cindy LetenUwe Himmelreich

Abstract

Tumor infiltrating stem cells have been suggested as a vehicle for the delivery of a suicide gene towards otherwise difficult to treat tumors like glioma. We have used herpes simplex virus thymidine kinase expressing human multipotent adult progenitor cells in two brain tumor models (hU87 and Hs683) in immune-compromised mice. In order to determine the best time point for the administration of the codrug ganciclovir, the stem cell distribution and viability were monitored in vivo using bioluminescence (BLI) and magnetic resonance imaging (MRI). Treatment was assessed by in vivo BLI and MRI of the tumors. We were able to show that suicide gene therapy using HSV-tk expressing stem cells can be followed in vivo by MRI and BLI. This has the advantage that (1) outliers can be detected earlier, (2) GCV treatment can be initiated based on stem cell distribution rather than on empirical time points, and (3) a more thorough follow-up can be provided prior to and after treatment of these animals. In contrast to rodent stem cell and tumor models, treatment success was limited in our model using human cell lines. This was most likely due to the lack of immune components in the immune-compromised rodents.

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Citations

Jul 28, 2016·Stem Cells and Development·Adam NowakowskiBarbara Lukomska
Sep 29, 2017·Frontiers in Immunology·Prakash Gangadaran, Byeong-Cheol Ahn
Nov 30, 2019·Neurosurgical Review·Ryota TamuraMasahiro Toda

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Methods Mentioned

BETA
xenograft
bioluminescence imaging
transgenic
fluorescence microscopy
protein assay
fluorescence imaging

Software Mentioned

GraphPad PRISM
GraphPad
living
Paravision
ImageJ

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