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Define stem cell

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


2 types of stem cell

1. embryonic (totipotent)
2. adult (or somatic, = mutlipotent)


Where are embryonic stem cells (ESCs) derived from?

- 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


How is the ICM amplified?

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


Pros - ESCs

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


Cons - ESCs

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


Name clinical trials for humans with ESCs

- 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)


What are adult stem cells?

- 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)


Pros - adult stem cells

- 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


Cons - adult stem cells

- hard to get enough cells
- still don't know how to generate all possible cell types


Function - adult stem cells

- replace worn out tissues
- replace damage tissues


examples - adult stem cell locaiton

- bone marrow (used to tx leukaemia)


Name 2 types of bone marrow stem cell

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


Where are adult stem cells found?

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


Define iPSc

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


Pros - iPSs

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


Cons - iPSs

- 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


What is DNA methylation?

important role for epigenetic gene regulation in development and disease


Therapeutic use - ESCs or adult stem cells - vet med

- 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


Describe use of stem cells in horse tendon ligament injury

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


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

- stem cell based tx licensed in USA (Vet-stem)
- derived from adipose tissue from an individual animal

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