Basics of Stem cells and Pluripotent Cells

Cells are basic units of life, we all know this. The life of all higher multi-cellular organisms begins with a single cell. This single cell is an undifferentiated but is capable to divide and produce all of the differentiated (or specialized) cells in an organism. Such cells are called Totipotent cells and this phenomenon is called Totipotency. For example, human life begins from the fertilized egg or zygote; which is a Totipotent cell. A zygote is capable to divide and give rise to all kinds of cells of human body.

A Totipotent cell gives rise to thousands of types of differentiated cells during the course of development. This differentiation is based upon genetics, environmental cues etc. The multicellular organisms are finally composed of two fundamental types of cells viz. somatic cells and the germ cells. During development, the somatic cells will become more specialized and form the three primary germ layers: ectoderm, mesoderm, and endoderm. After formation of the three germ layers, cells will continue to specialize until they reach a terminally differentiated state, capable to do the specific functions. This implies that as an organism grows, generic cells specialize in their own evolution and become cells of different organs such as eyes, heart, lungs, tissues etc.

On the other hand, the Germ cells undergo cellular differentiation into mature gametes, either eggs or sperm.

Stem Cells

The use of embryonic stem cells is controversial because their production destroys the embryo, which is considered as murder in some circles. Moreover, sometimes, to obtain stem cells for research the scientists have cloned embryos, leading to even more controversy.$The stem cells are also undifferentiated cells found only in multicellular organisms. These cells have the capability to divide and then get differentiated into different types of cells. In Mammals, there are two kinds of stem cells viz. embryonic and adult stem cells. The Embryonic stem cells are found in embryo of the organism. The modern medical science uses such cells by taking out from a developing embryo. At this stage, stem cells can convert into all of the specialized embryonic tissues, thus they are Totipotent.

On the other hand, the Adult stem cells act as a repair system for the body, replenishing specialized cells, but also maintain the normal turnover of blood, skin, and intestinal tissues. The most important source of adult stem cells is umbilical cord blood just after birth. The blood is collected from the umbilical cord of a newborn baby shortly after birth, with consent of the parents. This does not hurt the baby or the mother in any way. This blood would otherwise be discarded as biological waste along with the placenta, which is yet another rich source of stem cells. The umbilical cord blood contains haematopoietic
^{(capable to generate blood cells)} stem cells and which can be used to generate red blood cells and cells of the immune system. Cord blood stem cells are currently used to treat a range of blood disorders and immune system conditions such as leukaemia, anaemia and autoimmune diseases. These stem cells are used largely in the treatment of children but have also started being used in adults following chemotherapy treatment. Another type of cell that can also be collected from umbilical cord blood are mesenchymal stromal cells. These cells can grow into bone, cartilage and other types of tissues and are being used in many research studies to see if patients could benefit from these cells too. Umbilical cord blood can be collected and stored in a cord blood bank either in cord blood banks.

Apart from the above mentioned umbilical cord blood, placenta and mesenchymal stromal cells; there are other sources as mentioned below:

• Bone Marrow- Bone marrow is the source of haematopoietic cells. The cells are extracted by harvesting (drilling into the bone)
• Adipose tissue- where cells are extracted by liposuction
• Blood- where cells are extracted by passing blood through a special machine

The above introduction makes it clear that while the use of embryonic stem cell research is ethically controversial; the use of adult stem cells in research and therapy is not that much controversial. The primary reason is that the production / harvesting of the adult stem cells do not require the destruction of an embryo. Adult stem cells are often used in therapies like bone marrow transplantation and are artificially grown and transformed (converted) into specialized cell types by the use of tissue culture technologies. Tissue culture is a way of growing specific cells from stem cells artificially in a laboratory.

Cell Potency

Cell potency is the measure of a cell’s ability to convert into other cell types. The more cell types a cell can convert into, the higher potency it has. Over a cell’s lifetime, its potency decreases along a continuum of 5 levels.

At first, during embryonic stage the cell is Totipotency, we have discussed it above. Here a cell has the ability to specialize into all kinds of cells in the organism. It is possible for a fully differentiated cell to return to a state of Totipotency although the process is not well understood. The human zygote is the first totipotent cell.

One step down is pluripotency. At this stage the cell is capable of becoming many kinds of cells and tissues but not all. Stem cells can be either totipotent or Pluripotent, although multipotent or unipotent progenitor cells are sometimes referred to as stem cells also.

• Multipotent cells have the gene activation potential for many different types of cells but the variety is less than Pluripotent.
• Oligopotent cells can be activated into only a few types of cells.
• Finally unipotent cells are those, which have the capacity to convert into only one type of cell.

Induced Pluripotent stem cells

Induced Pluripotency is artificially achieved from a non-pluripotent cell – typically an adult somatic cell – by inducing a “forced” expression of specific genes.

Induced pluripotent stem cells or iPS cells or iPSCs are resemble natural Pluripotent stem cells, such as embryonic stem (ES) cells, in many aspects, but the full extent of their relation to natural Pluripotent stem cells is still being examined.

The production of iPSCs has been considered as an important advancement in stem cell research, as it may facilitate researchers to obtain Pluripotent stem cells, which are important in research and potentially have therapeutic uses, without the controversial use of embryos.

Researchers hope to use them to test drugs, to make models of diseases, to grow transplantable organs and, in the future they may be used by doctors to regenerate missing or damaged parts of their patient’s bodies.

Issue of Fraudulent Research claims in Stem Cells

Recently, papers by a team led by Dr. Haruko Obokata of the RIKEN Centre for Developmental Biology in Japan claimed that a simple way to reprogram ordinary mouse cells and thereby transforming themselves into pluripotent cells had been found by the researchers. Such a technique avoids the need to harvest them from embryos, their natural habitat, which is an ethically controversial matter (as discussed above).

In 2006, genes for proteins called transcription factors, which switch other genes on and off inside a cell, were used to make cultured skin cells Pluripotent. This process won for its creators the Nobel Prize in 2012 but it is a difficult and roundabout process. Dr Obokata’s papers suggested a simpler process instead. Her process involves shocking ordinary cells by placing them in a mild acid-bath.

Such a phenomenon where pluripotent stem cells are generated by subjecting ordinary cells to certain types of stress is called Stimulus-triggered acquisition of pluripotency (STAP), thus generated cells are called STAP Cells. However upon detailed peer review and further experimentation her method was found to be failure and papers were deemed as plagiarized and fraudulent.

Since then Dr. Obokata has had to apologize publicly for misleading the scientific community by “research misconduct” and by falsifying data. Obokata maintained her innocence and said she would fight the decision.

Fraudulent research in the this field is not new, earlier in 2006 the South Korean researcher Hwang Woo-Suk also fabricated a series of experiments and falsely reported to have created embryonic stem cells by cloning them.