Stem Cells

Question 1

(t) Describe the unique features of zygotic stem cells, embryonic stem cells and blood stem cells, correctly using the terms: Totipotency, Pluripotency, Multipotency

Answer 1

Stem Cells
Stem cells are unspecialized cells that can divide, during a single division, into two identical cells, of which one remains unspecialised, while the other one can undergo further differentiation into a specialised cell. When unspecialized stem cells divide and develop to specialized cells, the process is called cell differentiation.

Features of Stem Cells
Stem cells differ from other kinds of cells in the body. All stem cells, regardless of their source, have three general features:

(i) They are unspecialized.
A stem cell does not have any tissue-specific structures that allow it to perform specialized functions. However, unspecialized stem cells can give rise to specialized cells like heart muscle cells, blood cells, or nerve cells which play specific roles.

(ii) They are capable of dividing and renewing themselves for long periods.
Specialised cells like muscle cells, blood cells, or nerve cells do not normally replicate themselves. Stem cells may divide many times. Of the two daughter cells formed by mitosis of a stem cell, one cell remains unspecialised while the other differentiates.

(iii) They can give rise to specialized cell types.
The internal signals are controlled by a cell’s genes while the external signals for cell differentiation include chemicals secreted by other cells, physical contact with neighbouring cells, and certain molecules in the microenvironment.

Potency specifies the stem cell’s potential to differentiate into different cell types:

Totipotency :
Zygotic stem cells which have the ability to differentiate into any cell type to form whole organisms and so are also pluripotent and multipotent.

Pluripotency
Embryonic stem cells which have the ability to differentiate into almost any cell type to form any organ or type of cell and so are not totipotent but are multipotent.

Multipotency
Blood stem cells which have the ability to differentiate into a limited range of cell types and so are not pluripotent or totipotent.

Question 2

(u) Explain the normal functions of stem cells in a living organism including embryonic stem cells and blood stem cells.

Answer 2

(i) Embryonic stem (ES) cells

ES cells are obtained from the inner cell mass of a blastocyst.
ES cells obtained from the blastocyst are pluripotent, giving rise to all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm during development.
These germ layers subsequently give rise to the multiple specialized cell types that make up the heart, lung, skin, and other tissue.

ii) Blood / hematopoietic stem cells (Myeloid and lymphoid stem cells)
Adult stem cells are rare and few in numbers but have been identified in many organs and tissues. Adult stem cells are reported to be found in brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin and liver.

Their primary function is to maintain the steady state functioning of a cell by generating replacements for cells lost through disease, tissue injury or normal wear-and-tear.

Adult stem cells typically generate the cell types of the tissue in which they reside. A blood stem cell in the bone marrow, for example, normally gives rise to the many types of blood cells.
o Myeloid stem cells gives rise to red blood cells, platelets and white blood cells such as granulocytes.
o Lymphoid stem cells give rise to lymphocytes and white blood cells such as natural killer cells.

Question 3

(v) Discuss the ethical implications of the application of stem cells in research and medical applications and how human induced pluripotent stem cells (iPSCs) overcome some of these issues (procedural details of how iPSCs are formed are not required)

Answer 3

Ethical implications in the application of stem cells in research and medical applications:

Moral dilemma in using ES cells
The use of ES cells in researches poses a dilemma in the choice between two moral principles:
(1) to prevent or alleviate suffering or
(2) to respect the value of human life.
To obtain embryonic stem cells, the early embryo has to be destroyed and this means destroying a potential human life. However, ES cell research can also lead to new medical discoveries that may alleviate the suffering of many people.

Use of existing ES cell lines for research
This is a problematic issue as majority of these existing cell lines have become not truly pluripotent and majority of them are contaminated due to prolonged use. This makes them unsafe for transplantation into humans. Long standing cell lines have also been shown to accumulate mutations that may predispose the cells to cancer.

Confidentiality issues
Breaches in confidentiality may subject donors to unwanted publicity or harassment by different parties. Donors may thus wish to remain anonymous and this poses an issue when there is a need to trace information for research and development.

Induced pluripotent stem cell (IPSCs)

1. Features of IPSCs

• Adult cells (e.g. skin fibroblasts) that have been genetically reprogrammed to an embryonic stem cell-like state by being forced to express genes and proteins that allows them to maintain the properties of embryonic stem cells.
  o Human IPSCs are able to express proteins (stem cell markers) that characterises them as stem cells.
• Self-renewing and thus can divide and produce copies of themselves indefinitely.
• Pluripotent
  o Human IPSCs able to generate cells characteristic of all three germ layers.

Potential uses and Advantages of IPSCs

• Bioethics:
  Avoids the use of more controversial techniques
  o IPSCs can eventually provide cells reprogrammed from somatic cells (instead of harvesting from embryos) for research and treatment, circumventing the ethical issues behind the use of embryonic stem cells.
  o IPSCs may also enable scientists to avoid the use of other controversial methods, notably somatic cell nuclear transfer (cloning), a technique that has additional ethical considerations and that is extremely difficult to do routinely, as unfertilized human eggs are required.
• Genetically matched cell lines:
  Minimising cell/ tissue rejection issues
  o Patients’ own cells could be reprogrammed into IPSCs and then used to replace non-functional tissues.
  o Overcomes the problem where the body’s immune system recognises the implanted cells or tissues as foreign and attacks them.
  o Enhances the therapeutic application of cell-based therapies.
• Easier to create:
  o The technique can be performed in any moderately equipped molecular biology lab and does not require materials, such as human eggs or embryos that can be more difficult to obtain.
• IPSCs used as model for the study of diseases
  o Access to large numbers of particular cell types because cells from patients suffering from diseases can be reprogrammed to become IPSCs and then used as model cells for study the diseases (e.g. Type 1 diabetes and Parkinson’s disease).
  o For example, IPSCs are first reprogrammed from skin biopsies from Parkinson’s patients. These IPSCs are then used to produce neurons in the laboratory. These neurons have the same basic genetic make-up as the patients’ own cells. Thus scientist can directly work with neurons affected by Parkinson’s disease in a dish.

3. Limitations of IPSCs

• Not fully understood if IPSCs and ES cells differ in significant ways.
  o Several research groups have uncovered differences between IPSCs and ES cells in gene expression and other cellular functions like cell division.
  o This may be due to incomplete programming of the cells and/or genetic changes acquired by IPSCs as they grow and multiply.
• Safety issues need to be resolved as IPSCs can still become abnormal and be potentially unsafe for use in therapeutic procedures.
  o This is because IPSCs are reprogrammed using laboratory techniques. Such cells do not occur naturally during development.
  o Genetic changes that occur in the cells as IPSCs grow and multiply may be unpredictable.
  o Need for self-renewal property to be turned off before IPSCs can be used in therapies to avoid tumour formation.