Source: Yu, D. et al. Intranasal Delivery of Therapeutic Stem Cells to Glioblastoma in a Mouse Model. J. Vis. Exp. (2017)
This video demonstrates the intranasal delivery of oncolytic virus loaded therapeutic neural stem cells into a brain-tumor bearing mouse model. The non-invasive intranasal administration of stem cells bypasses the blood brain barrier, facilitating their delivery to the tumor site in the brain for therapeutic applications.
All procedures involving animal models have been reviewed by the local institutional animal care committee and the JoVE veterinary review board.
1. Hypoxic Preconditioning of Human NSCs (Figure 1A)
2. Loading of Human NSCs with Oncolytic Virus (Figure 1B-1H)
3. Intranasal Delivery of Therapeutic NSCs (Figures 1D and Figure 2D)
Figure 1: A flow chart for general stem cell preparation procedures involved prior to intranasal delivery. (A–C) Hypoxic pretreatment or genetic modifications of stem cells to overexpress CXCR4. (B–D) Washing, enzymatic dissociation, cell collection, and counting steps are performed for subsequent loading of stem cells with therapeutic or diagnostic cargo. (E) Therapeutic reagents, such as oncolytic viruses, or diagnostic tracers, such as MPIO particles, can be loaded in collected stem cells in appropriate concentrations with periodic shaking and gentle agitation (F). (G–I) The loaded stem cells can then be washed and counted for intranasal delivery into mice.
Figure 2: Schematic flow chart of the general animal procedures involved. (A) Tumor models are created via xenograft of patient derived glioma cells. (B) Tumor growth is monitored via BLI. (C) Head-only irradiation therapy is delivered (D) Supine and head-tilt posture is maintained during the therapeutic intranasal stem cell delivery. (E) Post therapy survival monitoring, small animal imaging and histological analysis of tissue if necessary are followed up.
The authors have nothing to disclose.
Cell culture supplies (Plastics) | ThermoFisher Scientific | Varies | Replaceable with any source |
Legend Micro 21R Refrigerated Microcentrifuge | ThermoFisher Scientific | 75002490 | Replaceable with any source |
Bench centrifuge Sorvall ST16R | ThermoFisher Scientific | 75004240 | Replaceable with any source |