Week 5: Stem Cell Therapy

Question 1

What are the main differences between embryonic and adult stem cells?

Answer 1

Embryonic Stem Cells
-origin: from inner cell mass of blastocyst
-unlimited self renewal capacity
-pluripotent
-iPS (induced pluripotent stem) cells: somatic adult cells forced into ES cell state. Expression of Oct4, Sox2, Klf4, c-Myc
Adult Stem Cells
-in body’s tissues, e.g. blood, brain, liver
-committed to becoming cell from tissue of origin
-can’t be grown indefinitely in lab

Question 2

Describe neural stem cells and list two main sties where neural stem cells reside in the adult brain

Answer 2

• type of adult stem cell
• self-renew, can produce neurons, astrocytes, oligodendrocytes
• found in sub ventricle zone of lateral ventricle and dentate gyrus of hippocampus
• can be derived from ES and iPS cells
• growth factors that promote propagation in lab: bFGF (basic fibroblast GF), EGF (epidermal gf), LIF (leukemia inhibitory factor), proteins that activate Wnt signaling

Question 3

What are the sources of neural stem cells?

Answer 3

1. fetal brain from aborted fetus
2. adult brain biopsy
3. Human ES cells
4. Human IPS cells
5. NCS from somatic cells via reprogramming

Question 4

What are the therapeutic approaches using neural stem cells for the treatment of neurological diseases and injuries?

Answer 4

• replace missing or damaged cells
• remyelination for e.g. spinal cord injury
• promotion of host tissue regeneration: parkinsons, stroke
• enzyme replacement therapy for neuroprotection
• tumor localized chemotherapy production
• drug discovery via stem cell based disease models

Question 5

What are the current limitations and challenges of neural stem cell therapy?

Answer 5

• generating pure populations of NSCs that are functionally equivalent to in vivo counterparts
• ensuring quality of NSCs and derivatives
• improving survival of implanted cells
• impact of cell delivery in host brain
• need to maintain existing connectivity while supporting new therapeutically relevant cell integration
• overcoming or using endogenous signals that impact fate of implanted cells
• overcoming scar formation

Question 6

How may stem cell therapy be used to treat Parkinson’s Disease?

Answer 6

• grafted dopaminergic neurons into striatum where there is normally lots of dopamine
• intrastriatal transplants of fetal mesencephalic tissue
• problems: lack of tissue for transplantation, variability in outcome, dyskinesias

Question 7

How may stem cell therapy be used to treat Spinal cord injury?

Answer 7

• grafts of NSCs engineered to secrete neurotrophic factors to support growth of host axons in injured spinal cord
• problems: lack of data, has produced functional improvements in animal models,