Biodistribution and persistence of human umbilical cord-derived mesenchymal stem cells in NCG mice: a comparative study.

INTRODUCTION

This study aims to investigate the biodistribution and persistence of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in NCG mice post-intravenous injection, utilizing Zr-PET/CT, bioluminescence imaging, multiplex immunohistochemistry (mIHC), and quantitative polymerase chain reaction (qPCR).

METHODS

hUC-MSCs were labeled with Zr-oxine (Zr-MSCs) or transduced with luciferase gene (Luc-MSCs). Real-time tracking of Zr-MSCs lasted for 14-days followed by mIHC staining of hCD73. Real-time tracking of Luc-MSCs lasted for 7-days, followed by mIHC staining of hCD73 and human Alu-based qPCR. All methods adhered to ICH and other regulatory guidelines for development of cell-based drugs.

RESULTS

A biodistribution and persistence pattern was observed in the order of lung > liver > kidney > >spleen, although discrepancies were noted for the liver and kidney.

CONCLUSION

Each method exhibited strengths and weaknesses: Zr-PET/CT enabled long-term tracking but encountered issues with Zr shedding and dead cells; bioluminescence provided specific detection but was hampered by a rapid decline in signal; mIHC identified cells but relied on antigen abundance; qPCR detected minimal cell quantities but was unable to differentiate between live and dead cells. These limitations may obscure the true fate of cells , highlighting the need for more accurate and reliable assessment techniques.