Lecture 8: Delivery Technology Flashcards
How can we deliver stem cells to the brain?
-Direct stereotactic injection (device allows you to target specific regions).
-Intravenous (May get trapped in lungs and may cause a pulmonary embolism).
-Intrarterial (IV injection with cells, hard to cross blood brain barrier).
-Intranasal
Describe why the intrarterial method may have issues/be difficult to perform.
-The blood brain barrier restricts the movement of many proteins and cells into the brain.
- So cells that could be beneficial following injury or disease may not reach the brain when administered peripherally
Blockage of arterial supply to brain tissue by cells: aka stroke
Describe why the intranasal method may have issues/be difficult to perform.
This is because they didn’t have enough data to support this. It did not provide much info. Results weren’t as reliable because genetically tagged mice were not used. Cells were dyed and contaminated so it was hard to tell which cell got the benefits.
Describe why the intravenous method may have issues/be difficult to perform.
May get trapped in lungs and may cause a pulmonary embolism.
Describe the experiment with the lipophilic dye
Took stem cells and incubated them with dye which makes cells green.
Put it in mouse nose and wait t2 weeks.
Section brain and observe
Based on morphology it is likely that the dye spread to other cells.
What they should have done instead: genetically tag with GFP that way it won’t spread to other cells.
How does intravenous delivery work?
Depends on the mechanisms involved: if the cells work primarily by modulating the immune response or other peripheral effects then IV delivery may well work.
Intrarterial delivery may work better for stem cells but not others
Ex. Mesenchymal stem cells may migrate across the blood brain barrier better than NCs
Describe stereotactic delivery
Surgery where stem cells are delivered through a needle.
Why is stereotactic delivery in rodents easier?
This is because adult inbred mice have very similar brain anatomy and thus stereotactic coordinates
Why is stereotactic delivery in humans more difficult?
This is because skull and brain anatomy in people can differ considerably so individual MRI-based coordinates are used.
Stereotactic injections/surgery is routinely performed in humans. Describe uses of stereotactic surgery in humans.
-Placement of deep brain stimulator for PD
-Biopsy of a tumor or epileptic foci
-Surgical resection of a tumor
-Stereotactic radio surgery
-Placement of a shunt to aid CSF drainage.
What are advantages of stereotactic delivery of stem cells?
-Targets the delivery of stem cells to the relevant brain region.
-Single delivery typically achieves good engraftment
-Compatible with all types of cells.
-Currently the only convincing way to deliver large numbers of stem cells to the brain.
What are disadvantages of stereotactic delivery of stem cells?
-Invasive nature/surgery
-Potential for serious complications (bleeding)
-Damage to tissue along needle tract
-Expensive
Important considerations for achieving good stereotactic delivery of stem cells.
-Start with a healthy cell population >95% viability to give the best chance of survival and reduce immune reactivity.
-Use appropriate gauge needle: not so small that you damage the cells but as small as possible. so less surrounding tissue damage (30-33 gauge).
Create a small pocket in the tissue for the cells to disperse into and inject cells and raise needle slowly to avoid injuring the cells or vacuuming them back up the needle tract.
Some cells are likely better than others at migrating to the CNS from the periphery.
But still not so great at migrating into the CNS even with a model with Robust inflammation and some blood brain barrier breakdown.
