Unit 2 Topic 3Cii Stem Cells

Question 1

Define stem cells

Answer 1

undifferentiated cells that can
1. undergo unlimited mitotic cell division to continuously divide and replicate into more stem cells
2. have the capacity to differentiate into specialised cell types

Question 2

What are three different types of stem cells and their potency

Answer 2

1. totipotent stem cells: undifferentiated cells that can differentiate into any type of cell needed for an entire new organism (including extraembryonic cells)
2. pluripotent stem cells: undifferentiated cells that can differentiate into most cell types needed for an entire new organism (except extra embryonic cells)
3. multipotent stem cells: undifferentiated cells that can differentiate into a very limited range of cells within a mature organism

Question 3

Examples of totipotent stem cells

Answer 3

• zygote
• morula

Question 3

Examples of pluripotent stem cells

Answer 3

• inner mass cells of a blastocyst

Question 3

Examples of multipotent stem cells

Answer 3

• adult stem cells
• cord blood stem cells

Question 4

What are unipotent stem cells

Answer 4

• can regenerate but can only differentiate into their associated cell type (liver stem cells can only make liver cells)

Question 5

How does a totipotent cell become pluripotent and multipotent?

Answer 5

1. undifferentiated cells become more differentiated and specialised by gene expression
2. some genes permanently switched off / inactivated due to epigentic modifications (histone modification, DNA methylation)
3. gene expression of active genes lead to synthesis of proteins / enzymes
4. proteins / enzymes synthesised cause structural and functional / metabolic change to the cell
5. cell’s function is permanently modified ==> multipotent stem cell

Question 6

Define morula

Answer 6

an early embryo (3-4 days after fertilisation) made up of solid ball of 10-30 totipotent cells

Question 7

Define blastocyst

Answer 7

an early embryo (5-6 days after fertilisation) consisting a hollow ball of cells with an inner cell mass of pluripotent cells

Question 8

Define trophoblast

Answer 8

outer layer of cells, develops into the placenta

Question 9

What is inner cell mass

Answer 9

• with pluripotent cells, develops into fetus
• source of pluripotent embryonic stem cells
• loss of potency due to gene expression (cannot differentiate)

Question 10

Express the formation of blastocyst

Answer 10

occurs in the fallopian tubes and uterus prior to implantation

1. when blastocyst reaches the uterus, it embeds itself in the uterus lining (endometrium)
2. once implanted, developing embryo will gain nutrients and oxygen from endometrium tissue fluid which is supplied by the endometrium’s capillary network

Question 11

Why are embryonic stem cells pluripotent instead of totipotent inthe morula?

Answer 11

• embryonic stem cells are found in the inner stem cell mass of the blastocysts

1. some genes are permanently switched off when the morula develops into blastocyst
2. embryonic stem cells are pluripotent ==> undifferentiated cell that can form most cell types needed for an entire new organism (except extra embryonic cells)

Question 12

Define embryonic stem cells

Answer 12

Inner stem cell mass of blastocyst have embryonic stem cells which are pluripotent

Question 13

What are some challenges of using embryonic stem cells

Answer 13

• ethical dilemmas: involves the destruction of an embryo
• possible immune rejection after implantation (cell do not originate from the patient)
• mutations have been observed in stem cells cultered for number of generations, some observed to develop into or behave like cancer cells

Question 14

Where are umbilical cord stem cells present?

Answer 14

• blood draining from placenta and umbilical cord after birth have umbilical cord stem cells which are pluripotent

Question 15

How are umbilical cord stem cells made available for stem cell therapy

Answer 15

• blood is frozen and stored
• stem cells will be available for the child for stem cell therapy

Question 16

What are some challenges and difficulties to use umbilical cord stem cells

Answer 16

1. expensive cost
2. long-term storage space is needed
3. very little evidence of cord blood being used successfully to treat anyone (precursor cells of conditions like leukemia are already present in the blood at birth)
4. the umbilical cord harvested depends on mother or baby’s consent?

Question 17

Examples of adult stem cells / somatic stem cells

Answer 17

1. haemotapoietic stem cells
2. neural stem cells
3. skin stem cells

Question 18

Difficulties of using somatic stem cells

Answer 18

1. difficult to extract (few, buried deep in tissues)
2. limited capacity to differentiate
3. higher chance of genetic damage (due to accumulation of mutations throughout life of adult)
4. need to find a stable donor (preferably close to recipient) (minimuse chance of immune rejection)

Question 19

What are some conditions that can be treated with traditional stem cell therapy

Answer 19

1. Stargardt’s mascular dytrophy
2. Leukemia

Question 20

What is Stargardt’s mascular dystrophy

Answer 20

• recessive genetic condition affecting 1 in 10000 children
• mutation causes active transport protein on photoreceptor cell to malfunction and degenerate
• photoreceptor cells degenerate
• progressive and eventually total loss of central vision

Question 21

Treatment process for Stargardt’s mascular dystrophy

Answer 21

1. embryonic stem cells used to divide and differentiate into retinal cells
2. retinal cells injected into retina
3. retina cells attach to retina and become functional
4. central vision improves (more functional retinal cells)

Question 22

What is leukemia

Answer 22

cancer of blood or bone marrow, resulting in abnormally high levels of poorly-functioning white blood cells

Question 23

Treatment process of leukemia

Answer 23

1. haematopoietic stem cells harvested from **bone marrow, peripheral blood, umbilical cord blood** 2. **chemotherapy and radiotherapy** used to destroy diseased white blood cells 3. new white blood cells need to be replaced with healthy cells 4. HSCs **transplanted back** to bone marrow 5. HSCs **divide and differentiate** into new healthy white blood cells

Question 24

Pros of treating leukemia with traditional stem cell therapy

Answer 24

- patients are using their own haematopoietic stem cells - less risk of immune rejection than with a traditional bone marrow transplant

Question 25

Cons of treating leukemia with traditional stem cell therapy

Answer 25

treated patients are at higher risk of developing other cancers

Question 26

How does therapeutic cloning (somatic cell cloning) works

Answer 26

produce large quantities of healthy cloned cells / tissues

Question 27

Outline the process of therapeutic cloning (somatic cell cloning)

Answer 27

1. remove the nucleus from a **normal, healthy body cell** and transfer it to an **enucleated human ovum** 2. use **mild electric shock** to fuse the nucleus with enucleated ovum and trigger **development** 3. **pluripotent stem cells are harvested** from embryo formed, cultured in suitable environemtn = **differentiate into required tissue** 4. tissue **transferred** to the patient

Question 28

Will there be a problem of immune rejection for therapeutic cloning? Explain.

Answer 28

No. Because the cells have the same genotype as the patient

Question 29

Does the genetic information differ from the patient since development is triggered in another ovum.

Answer 29

- the ovum is **enucleated** - nucleus transferred is **from the patient** - newly formed cell develops and divdes, producing a collection of identical cells **with the same genetic information as the patient** - clone is simply a source of stem cells with **genetic markers that match the patient perfectly**

Question 30

How to obtain stem cells in therapeutic cloning

Answer 30

- use **somatic cell nuclear transfer (SCNT)** to *combine* a patient's somatic cell nucleus and enucleated human egg cell - forming an **embryo** => obtain **stem cells**

Question 31

Limitations of therapeutic cloning

Answer 31

1. treatment at the **experimental stage** of development (still determining the exact triggers controlling cell differentiation) 2. **shortage** of donor eggs 3. **ethical objections** to use donor eggs 4. therapeutic cloning could be used to **clone a human** => ethical concerns 5. adult stem cells nucleus needs to be **genetically modified before adding** to enucleated ovum, or else **carry the genetic mutation causing disease** / problem in the first place

Question 32

How does the Induced pluripotent stem cells (iPS cells) work

Answer 32

- reprogramming of human somatic cells to form induced pluripotent stem cells

Question 33

Define transdifferentiation

Answer 33

conversion of cells from one differentiated cell type to another

Question 34

Pros of iPS cells

Answer 34

- **overcomes ethical objections** of using embryonic tissues as source of stem cells (no killing embryo involved) - **no immune rejection** as patients use their own cells to provide own stem cells

Question 35

Cons of iPS cells

Answer 35

- **difficult** to **make** iPS cells - **difficult** to make iPS cells **differentiate into desired** tissue - conditions not know yet / not enough experience (most successful work are **done on embryonic stem cells** / not sure how long **will they behave as pluripotent stem cells**) - transplanted iPS stem cells can divide uncontrollably, potentially becoming **cancerous**

Question 36

Define gene therapy

Answer 36

treatment of disease by adding a missing gene / replacing or altering a faulty gene in affected cells

Question 37

Suggest two methods and their mechanisms that genetic disease can be treated by obtaining cells from patients

Answer 37

1. **therapeutic cloning**: modify adult stem cells nucleus before adding it to an empty ovum => cultured stem cells will not carrying faulty genes 2. **iPS cells**: reprogramming somatic cells => induction of pluripotency ==> iPS cells => gene correction ==> cell differentiation ==> transplant into patient

Question 38

What is Parkinson's disease

Answer 38

- common age-related brain disorder - nerve cells in the brain, **dopamine neurons** that signal the production of dopamine (neurotransmitter hormone) **stop working** + lost - **fall of dopamine levels** ==> develop **uncontrollable tremors** in hands and body

Question 39

How can Parkinson's disease be treated with stem cell therapy

Answer 39

- using pluripotent stem cells - impant **pluripotent stem cells into brain** - cell divide and **differentiate into dopamine neurons** - release dopamine - dopamine production restored

Question 40

What is Type 1 Diabetes

Answer 40

- develops when people are young - glucose-sensitive, **insulin-secreting cells from the islets of Langerhans in the pancreas** are destroyed - stop producing insulin - blood glucose cannot be controlled

Question 41

How can Type 1 Diabetes be treated with stem cell therapy

Answer 41

- using human embryonic stem cells - cells develop into mature human glucose-sensitive insulin-producing beta cells - replace malfunctioning cells - restore insulin production and control blood glucose level

Question 42

Where are the glucose in blood converted and stored?

Answer 42

- glucose in blood will be converted into glycogen - stored in the liver and muscle cells

Question 43

What is the problem with damaged nerves

Answer 43

- destoyed nerves in the brain and spine do not regrow - potential permanent paralysis

Question 44

How can damaged nerves be treated with stem cell therapy?

Answer 44

- using stem cells - transplant, differentiate, replacing damaged nerves - patients may regain a certain amount of control and movement of limbs that have been paralysed

Question 45

What is beneficence

Answer 45

the aim of doing good, by giving medicine to relieve suffering

Question 46

What is non-maleficence

Answer 46

doing no harm

Question 47

Give arguments to support stem cell therapy

Answer 47

1. paves way for **future discoveries and beneficial technologies** 2. **cure serious disease or disabiity** by replacing defective cells with working ones 3. stem cell donation **do not directly cause death** of another human 4. stem cells can be taken from **embryo that have stopped developing** or would have died (abortion) 5. cells are taken at a stage where the embryo has **no nervous system** => arguable feel no pain 6. iPS cells can be created **without the need of fertilisation and destruction of human embryos** 7. stem cells are **less likely** to be **rejected by the immun system** as they are cells which are **genetically identical** to the patients

Question 48

What are the disadvantages of organ transplant

Answer 48

1.high chance rejected by immune system - **glycoproteins on the surface of cell membrane** are responsible for cell recogniition - immun system recognises its own cells + **destroy nonself cells** - lethal for organ transplants - people who received organ transplants **take immunosuppressant drugs** for the rest of their lives = **risk for infectious disease** 2.hard to find donor - donor have to have **matching blood groups, antigen, consent form** 3.**limited range of organs** which can be used

Question 49

Give arguments against stem cell therapy

Answer 49

1. **limited knowledge** on how genes in stem cells are switched on or off to form specific types of cell / tissue 2. could cause **development of cancer** if divide uncontrollably 3. involves **creation and destruction** of human embryos 4. **excess embryos are killed** (generally produced more than needed) 5. embryo can be **used in IVF** and to develop into a fetus instead 6. **other technologies** may fulfill similar roles (nuclear reprogramming of differentiated cell lines) 7. **religious** objections 8. cloning humans reproductively is **illegal** (therapeutic cloning)

Question 50

Define cleavage

Answer 50

- final embryonic development - involves special kind of mitosis where cells divide repeatedly without normal interphase for growth between divisions - result: formation of blastocyst

Question 51

Outline the development from zygote to blastocyst

Answer 51

Zygote - formed due to fertilisation - totipotent morula - zygote undergo mitotic division by 4th day after fertilisation - totipotent blastocyst (hollow ball of cells) - continue to divide by mitosis - 1-2 days - pluripotent

Question 52

What are the structures of a blastocyst

Answer 52

- inner cell mass - fluid-filled cavity - zona pellucida - trophoblast

Question 53

Formation and implantation of blastocyst

Answer 53

- formation occurs in fallopian tubes / **oviduct and uterus** *prior to* implantation - embeds itself in **uterus lining** once reaches uterus - implanted => **gains nutrients and oxygen** from endothelium tissue fluid (supplied by endometrium's capillary network)

Question 54

How can stem cell therapy make advancements for patients that requires organ transplant

Answer 54

- allow organs to be grown from patient's own stem cells

Question 55

Suggest advantages of using stem cell therapy over traditional organ transplant

Answer 55

- no problem of rejection from immune system if using patient's own stem cells - surgery less invasive than traditional organ translantation surgery - recovery time is shorter

Question 56

(past paper) Scientists are developing ways of using stem cells to replace heart cells that have been damaged as a result of heart disease. Both embryonic stem cells and induced pluripotent stem cells can be used to create new heart cells. **Compare and constrast the properties and uses of embryonic stem cells with those of iPS cells.** (5)

Answer 56

similarties - both have potential to **divide indefinitel**y - both have potential to **differentiate into a number of cell types** differences - iPS cells were **adult cellls** but embryonic stem cells are taken from the **morula** - iPS have a **gene** but embryonic cells do not - less **ethical issues** surrounding the use of iPS cells - iPS cells form **adult** cells, embryonic cells form **younger** cells - iPS produce **patient-matched** cells, embryonic stem cells are **antigenic**

Question 57

(past paper) The dachshund is a breed of dog that is at higher risk of paralysis due to spinal injury. Suggest why stem cells can be used to reverse this paralysis. (2)

Answer 57

- stem cells are pluripotent - can specialise or differentiate to differentiated cells - the differentiated cells can replace damaged cells in the spinal cord of the Dachshund - new nervous tissues can be formed - capable of continuous division (no Hayflick limit)

Question 58

(past paper) A trial experiment was carried out on a dog that was paralysed due to spinal injury and was unable to use its back legs. The scientists extracted stem cells from the lining of the dog's nose. These cells were cultured for a month to increase their numbers. The stem cells were then injected to the injury site of the dog. **Suggest why stem cells were taken from this dog and not from another dog (2)**

Answer 58

- cells are genetically identical with the same genotype - can avoid immune response and rejection from the immune system - no need for immunosuppressant drugs - no disease transmission (reduced risk of

Question 59

（past paper) A further investigation was carried out on 34 dogs with spinal injuries. Some had stem cells injected into the site of spinal injury. The others were injected with fluid containing no stem cells, called neutral fluid. (i) Explain the reason for giving some of the dogs a neutral fluid instead of stem cells. (2) (ii) The scientists nor the owners knew which dogs had been given stem cells or not. Explain. (2)

Answer 59

(1) Placebo, used as a control to compare with teh stem cell treatment (2) to remove bias, making it a double blond trial

Question 60

(past paper) Stem cells are required for the development of medical therapies. Suggest two applications of the use of stem cell therapy.

Answer 60

1. produce transplant organs 2. repair or replace damaged tissues