Stem cell treatments

Question 1

Define stem cell

Answer 1

an unspecialised cell with ability to self-renew and the capability of differentiating into multiple cell types

Question 2

2 types of stem cell

Answer 2

1. embryonic (totipotent)

2. adult (or somatic, = mutlipotent)

Question 3

Where are embryonic stem cells (ESCs) derived from?

Answer 3

• the ICM of the blastocyst
• in most mammals there are only a v small # of cells in the ICM and there is only a short period of time before they begin to differentiate
• need to be amplified for therapeutic benefit

Question 4

How is the ICM amplified?

Answer 4

removed and cultured in conditions that keep them dividing but not differentiating, cells are passaged when confluent. Over a period of months, enough cells harvested to be of use. Cultures can be grown indefinitely as cells have a limitless capacity to self-renew and thus each ICM can lead to a new stem cell line. Cellls can be induced to differentiate by adding different gorwht facotrs and supplements to the media and/or encouraging cells to cluster in an embryoid body

Question 5

Pros - ESCs

Answer 5

• generate vast #s cells with capacity to make any of 200+ cell types in body

Question 6

Cons - ESCs

Answer 6

• takes long time to grow sufficient #s from individual embryo
• if implanted into lesion may differentiate into incorrect tissue or form a teratoma

Question 7

Name clinical trials for humans with ESCs

Answer 7

• macular degeneration (partially differentiated ESCs injected into eye)
• diabetes (incorporating ESCs into medical device, it is semi-permeable, nutrients in/out, less vulnerable to attack by immune system)

Question 8

What are adult stem cells?

Answer 8

• undifferentiated cells that can be found amongst differentiated cells in many (possibly all) adult tissues
• any SC found in a postnatal organ is classified as adult
• normal tissue they tend to be dormant (non-proliferating)
• often induced to proliferate upon injury
• don’t have infinite capacity to keep dividing (unlike ESCs)
• limited number of derivatives (most have only 2 derivatives, maybe 3/4 in culture)

Question 9

Pros - adult stem cells

Answer 9

• cna harvest ‘own’ stem cells reducing the likelihood of rejection
• more limited capacity means you won’t be forming teratomas
• amplification is difficult as don’t proliferate fast/ indefinitely
• few ethical concerns

Question 10

Cons - adult stem cells

Answer 10

• hard to get enough cells

- still don’t know how to generate all possible cell types

Question 11

Function - adult stem cells

Answer 11

• replace worn out tissues

- replace damage tissues

Question 12

examples - adult stem cell locaiton

Answer 12

• bone marrow (used to tx leukaemia)

Question 13

Name 2 types of bone marrow stem cell

Answer 13

1. ) Haematopoietic (forms all types of blood cell)
2. ) Bone marrow stromal cells/ mesenchymal stem cells / skeletal stem cells = make up small % stromal cells in BM, can generate bone, cartilage and fat cells that support the formation of blood and fibrous CT

Question 14

Where are adult stem cells found?

Answer 14

• bone marrow
• skin
• adipose tissue
• brain
• peripheral blood
• BVs
• skeletal mm
• teeth
• heart
• gut
• liver
• testes
• ovarian epithelium

Question 15

Define iPSc

Answer 15

Induced pluripotent stem cells

• they are adult somatic cells (usually fibroblasts) that have been transfected with a viral vector carrying a stem cell gene
• once expressed, these instruct the cell to become ‘embryonic’ again

Question 16

Pros - iPSs

Answer 16

• easy to obtain and transform into stem cells
• can be amplified
• could be personalised (obtained from and used for oneself)

Question 17

Cons - iPSs

Answer 17

• retain adult epigenetic profiles of methylation so don’t become fully embryonic
• prematurely age
• die
• poor proliferation profiles vs ESCs
• do seem to be rejected in animals they were derived from

Question 18

What is DNA methylation?

Answer 18

important role for epigenetic gene regulation in development and disease

Question 19

Therapeutic use - ESCs or adult stem cells - vet med

Answer 19

• many ongoing clinical trials
• horse tendon or ligament injury
• horse or dog bone/joint/tendon injury
• both cases it may be that the stem cells don’t physically take part in forming new tissues but may produce factors that promote tissue healing

Question 20

Describe use of stem cells in horse tendon ligament injury

Answer 20

• repair of tendon injury using BM derived from mesenchymal SCs from individual horse
• marrow from sternum
• licensed by a UK company (VetCell)

Question 21

Describe use of stem cells in canine bone/joint/ tendon injury

Answer 21

• stem cell based tx licensed in USA (Vet-stem)

- derived from adipose tissue from an individual animal