Stem Cell Therapy

Question 1

Hierarchy of Cells

Answer 1

1- ES (embryonic stem cells) - highest differentiation potential b/c can become all cell types in body

2- Tissue specific cells - can become all cell types of that specific tissue (multipotent)

3- Transit Amplifying Precursor Cells - multipotent but more restricted; limited to one or few types of cells in that tissue

4- Differentiated/ somatic cells - stopped dividing and have little capacity to divide

Question 2

2 Options of ES and iPS Cells in Replication and What Causes One Over Other?

Answer 2

1- self renewal (make another stem cell)

2- differentiation (daughter cell is more specific)

**2 daughter cells from same original cell can have diff outcomes depending on the intrinsic and extrinsic factors in the vicinity

Question 3

Reprogramming

Answer 3

Process by which somatic cells of embryos or adults are exposed to a small number of genes that make them pluripotent again

**Must repress differentiated genes and de-repress pluripotent genes

Question 4

3 Ways of Manipulating Stem Cells Before Transplantation

Answer 4

1- CRISPR - correct genes w/ specific targeting (you make guide mRNA)
2- Partial differentiation (prevents ES and iPS cells from forming teratomas)
3- Sorting (use cell surface markers to select for certain type out of a mixed sample)

Question 5

Direct Lineage Conversion

Answer 5

• Alternative to using iPS
• Faster than iPS and fewer places for things to go wrong b/c skip intermediate
• “Transdifferentiation” - use gene transfer to convert one type of somatic cell to another
• Limited in # of appropriate cells generated

Question 6

Why and how could stem cells be used for INCL?

Answer 6

Infantile neuronal ceroid lipofuscinsis

Enzyme replacement therapy does not help CNS symptoms b/c cannot cross blood brain barrier

Use normal human embryonic CNS cells for global delivery of good enzyme

Trials showed they migrated and integrated into host cell

Question 7

Why and how could stem cells be used for HD?

Answer 7

No current alternative treatment (just symptom alleviation)

In HD, medium spiny neurons affected so could use iPS and turn them into medium spiny neuron precursors

EXPENSIVE but could create bank of HLA-matched iPS cells (HLA match means dec in immune response)