Unit 2 Topic 3Cii Stem Cells Flashcards
Define stem cells
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
What are three different types of stem cells and their potency
- totipotent stem cells: undifferentiated cells that can differentiate into any type of cell needed for an entire new organism (including extraembryonic cells)
- pluripotent stem cells: undifferentiated cells that can differentiate into most cell types needed for an entire new organism (except extra embryonic cells)
- multipotent stem cells: undifferentiated cells that can differentiate into a very limited range of cells within a mature organism
Examples of totipotent stem cells
- zygote
- morula
Examples of pluripotent stem cells
- inner mass cells of a blastocyst
Examples of multipotent stem cells
- adult stem cells
- cord blood stem cells
What are unipotent stem cells
- can regenerate but can only differentiate into their associated cell type (liver stem cells can only make liver cells)
How does a totipotent cell become pluripotent and multipotent?
- undifferentiated cells become more differentiated and specialised by gene expression
- some genes permanently switched off / inactivated due to epigentic modifications (histone modification, DNA methylation)
- gene expression of active genes lead to synthesis of proteins / enzymes
- proteins / enzymes synthesised cause structural and functional / metabolic change to the cell
- cell’s function is permanently modified ==> multipotent stem cell
Define morula
an early embryo (3-4 days after fertilisation) made up of solid ball of 10-30 totipotent cells
Define blastocyst
an early embryo (5-6 days after fertilisation) consisting a hollow ball of cells with an inner cell mass of pluripotent cells
Define trophoblast
outer layer of cells, develops into the placenta
What is inner cell mass
- with pluripotent cells, develops into fetus
- source of pluripotent embryonic stem cells
- loss of potency due to gene expression (cannot differentiate)
Express the formation of blastocyst
occurs in the fallopian tubes and uterus prior to implantation
- when blastocyst reaches the uterus, it embeds itself in the uterus lining (endometrium)
- once implanted, developing embryo will gain nutrients and oxygen from endometrium tissue fluid which is supplied by the endometrium’s capillary network
Why are embryonic stem cells pluripotent instead of totipotent inthe morula?
- embryonic stem cells are found in the inner stem cell mass of the blastocysts
- some genes are permanently switched off when the morula develops into blastocyst
- embryonic stem cells are pluripotent ==> undifferentiated cell that can form most cell types needed for an entire new organism (except extra embryonic cells)
Define embryonic stem cells
Inner stem cell mass of blastocyst have embryonic stem cells which are pluripotent
What are some challenges of using embryonic stem cells
- 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
Where are umbilical cord stem cells present?
- blood draining from placenta and umbilical cord after birth have umbilical cord stem cells which are pluripotent
How are umbilical cord stem cells made available for stem cell therapy
- blood is frozen and stored
- stem cells will be available for the child for stem cell therapy
What are some challenges and difficulties to use umbilical cord stem cells
- expensive cost
- long-term storage space is needed
- 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)
- the umbilical cord harvested depends on mother or baby’s consent?
Examples of adult stem cells / somatic stem cells
- haemotapoietic stem cells
- neural stem cells
- skin stem cells
Difficulties of using somatic stem cells
- difficult to extract (few, buried deep in tissues)
- limited capacity to differentiate
- higher chance of genetic damage (due to accumulation of mutations throughout life of adult)
- need to find a stable donor (preferably close to recipient) (minimuse chance of immune rejection)
What are some conditions that can be treated with traditional stem cell therapy
- Stargardt’s mascular dytrophy
- Leukemia
What is Stargardt’s mascular dystrophy
- 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
Treatment process for Stargardt’s mascular dystrophy
- embryonic stem cells used to divide and differentiate into retinal cells
- retinal cells injected into retina
- retina cells attach to retina and become functional
- central vision improves (more functional retinal cells)
What is leukemia
cancer of blood or bone marrow, resulting in abnormally high levels of poorly-functioning white blood cells
Treatment process of leukemia
- haematopoietic stem cells harvested from bone marrow, peripheral blood, umbilical cord blood
- chemotherapy and radiotherapy used to destroy diseased white blood cells
- new white blood cells need to be replaced with healthy cells
- HSCs transplanted back to bone marrow
- HSCs divide and differentiate into new healthy white blood cells
Pros of treating leukemia with traditional stem cell therapy
- patients are using their own haematopoietic stem cells
- less risk of immune rejection than with a traditional bone marrow transplant
Cons of treating leukemia with traditional stem cell therapy
treated patients are at higher risk of developing other cancers
How does therapeutic cloning (somatic cell cloning) works
produce large quantities of healthy cloned cells / tissues
Outline the process of therapeutic cloning (somatic cell cloning)
- remove the nucleus from a normal, healthy body cell and transfer it to an enucleated human ovum
- use mild electric shock to fuse the nucleus with enucleated ovum and trigger development
- pluripotent stem cells are harvested from embryo formed, cultured in suitable environemtn = differentiate into required tissue
- tissue transferred to the patient
Will there be a problem of immune rejection for therapeutic cloning? Explain.
No. Because the cells have the same genotype as the patient
Does the genetic information differ from the patient since development is triggered in another ovum.
- 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
How to obtain stem cells in therapeutic cloning
- 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
Limitations of therapeutic cloning
- treatment at the experimental stage of development (still determining the exact triggers controlling cell differentiation)
- shortage of donor eggs
- ethical objections to use donor eggs
- therapeutic cloning could be used to clone a human => ethical concerns
- 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
How does the Induced pluripotent stem cells (iPS cells) work
- reprogramming of human somatic cells to form induced pluripotent stem cells
Define transdifferentiation
conversion of cells from one differentiated cell type to another
Pros of iPS cells
- 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
Cons of iPS cells
- 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
Define gene therapy
treatment of disease by adding a missing gene / replacing or altering a faulty gene in affected cells
Suggest two methods and their mechanisms that genetic disease can be treated by obtaining cells from patients
- therapeutic cloning: modify adult stem cells nucleus before adding it to an empty ovum => cultured stem cells will not carrying faulty genes
- iPS cells: reprogramming somatic cells => induction of pluripotency ==> iPS cells => gene correction ==> cell differentiation ==> transplant into patient
What is Parkinson’s disease
- 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
How can Parkinson’s disease be treated with stem cell therapy
- using pluripotent stem cells
- impant pluripotent stem cells into brain
- cell divide and differentiate into dopamine neurons
- release dopamine
- dopamine production restored
What is Type 1 Diabetes
- 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
How can Type 1 Diabetes be treated with stem cell therapy
- 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
Where are the glucose in blood converted and stored?
- glucose in blood will be converted into glycogen
- stored in the liver and muscle cells
What is the problem with damaged nerves
- destoyed nerves in the brain and spine do not regrow
- potential permanent paralysis
How can damaged nerves be treated with stem cell therapy?
- using stem cells
- transplant, differentiate, replacing damaged nerves
- patients may regain a certain amount of control and movement of limbs that have been paralysed
What is beneficence
the aim of doing good, by giving medicine to relieve suffering
What is non-maleficence
doing no harm
Give arguments to support stem cell therapy
- paves way for future discoveries and beneficial technologies
- cure serious disease or disabiity by replacing defective cells with working ones
- stem cell donation do not directly cause death of another human
- stem cells can be taken from embryo that have stopped developing or would have died (abortion)
- cells are taken at a stage where the embryo has no nervous system => arguable feel no pain
- iPS cells can be created without the need of fertilisation and destruction of human embryos
- stem cells are less likely to be rejected by the immun system as they are cells which are genetically identical to the patients
What are the disadvantages of organ transplant
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
Give arguments against stem cell therapy
- limited knowledge on how genes in stem cells are switched on or off to form specific types of cell / tissue
- could cause development of cancer if divide uncontrollably
- involves creation and destruction of human embryos
- excess embryos are killed (generally produced more than needed)
- embryo can be used in IVF and to develop into a fetus instead
- other technologies may fulfill similar roles (nuclear reprogramming of differentiated cell lines)
- religious objections
- cloning humans reproductively is illegal (therapeutic cloning)
Define cleavage
- final embryonic development
- involves special kind of mitosis where cells divide repeatedly without normal interphase for growth between divisions
- result: formation of blastocyst
Outline the development from zygote to blastocyst
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
What are the structures of a blastocyst
- inner cell mass
- fluid-filled cavity
- zona pellucida
- trophoblast
Formation and implantation of blastocyst
- 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)
How can stem cell therapy make advancements for patients that requires organ transplant
- allow organs to be grown from patient’s own stem cells
Suggest advantages of using stem cell therapy over traditional organ transplant
- 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
(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)
similarties
- both have potential to divide indefinitely
- 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
(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)
- 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)
(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)
- 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
（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)
(1) Placebo, used as a control to compare with teh stem cell treatment
(2) to remove bias, making it a double blond trial
(past paper) Stem cells are required for the development of medical therapies. Suggest two applications of the use of stem cell therapy.
- produce transplant organs
- repair or replace damaged tissues
