Tissue Repair 2 - Stem Cells to Regenerate the Brain Flashcards
What neurons are dying in parkinsons?
- the ones that make dopamine
How can you detect Parkinson’s?
- by doing a floro dopa PET scan
- dopa = precursor to dopamine
Where is the dopamine produced?
Striatum
What are the two subdivides of the striatum?
- caudate
- Putamen
Where are dopamine producing cells originally made?
Substantia nigra
What is happening in parkinsons?
- nigral dopaminergic neurons are lost
- these neurons supply dopamine to the putamen in the striatum
What are 2 sources of dopamergic neurons for transplantation?
- ventral midbrain tissue from foetus
- midbrain DA neurons from human embryonic stem cells
Explain the 6-hydroxydopamine (6-OHDA) lesion rat model of Parkinson’s
First surgery
- kill substantial niagron neurons on one side
Second surgery
- transplant cells into the striatum
Explain amphetamine-induced unilateral rotations
- when on amphetamine will run in circles
- when cured, no circles just hyper
What is the effect of the age of the foetus on the second surgery?
If the foetus was more mature, it was less successful
What two stem cells could be used for transplanting in parkinsons?
- embryonic stem cells (ESCs) - from embryos from IVF
- induced pluripotent stem cells (iPSCs) - from adult blood or skin cells
What are the qualities of ESCs and iPSCs?
- immortal
- stable chromosomes
- can produce all cell types
Explain the development of midbrain from ESCs and iPSCs
Time 0
- dual smad inhibition -> anterior tissue
- high SHH -> ventral
- Wnt -> caudal
- will default to neural tissue
- FGF8 -> midbrain
- makes midbrain DA neurons
What midbrain markers do you want to see in stem cell cultures?
- Lmx1a
- FOXA2
- no NKX 6.1
- CORIN - can flow cytrometry
when should stem cells be transplanted into the striatum?
day 16
