Preclinical study reveals intra-arterial delivery of nanobody-secreting stem cells targets injured brain tissue, indicating therapeutic promise for post-injury neuroinflammation.
Key Points
To engineer mesenchymal stem cells to secrete a P2X7 receptor-blocking nanobody and evaluate their delivery, persistence, and safety in a mouse model of traumatic brain injury.
Transfected primary mesenchymal stem cells with bicistronic mRNA encoding a P2X7-blocking nanobody and labeled them with iron oxide nanoparticles.
Administered labeled stem cells via intra-arterial carotid injection in mice 24 hours after closed-head injury, tracking accumulation via dynamic 9.4 T susceptibility-weighted MRI over 3 days.
Assessed motor function using the beam walk test and confirmed cellular localization in brain tissue using immunofluorescence 4 days post-injury.
Achieved 38.9% in vitro transfection efficiency, yielding peak P2X7-blocking nanobody secretion of 17.29 ± 1.84 ng/mL.
MRI confirmed persistent accumulation of labeled stem cells in the injured brain, with hypointense signals covering 2.45% ± 2.93% to 0.77% ± 0.88% of the right hemisphere over 3 days.
Beam walk testing revealed no cell transplantation-related motor impairments, and histology confirmed the presence of engineered stem cells within injured brain tissue.
Cite This Study
Fadon‐Padilla et al. (2026) studied this question.