Induced pluripotent stem cells

Induced pluripotent stem cells (iPSCs) are adult cells that have been genetically reprogrammed to an embryonic stem cell–like state. This is done by forcing them to express genes and factors similar to embryonic stem cells. This is like taking the cells back in time. Although these cells meet the defining criteria for pluripotent stem cells, it is not known if iPSCs and embryonic stem cells differ in clinically significant ways.

Induced pluripotent stem cells (iPSCs) have great potential uses in medicine. They can provide perfect stem cells for a patient when no compatible donor is available. It is not possible to get a perfect match in organ donation apart from identical twins.

Unique properties of all stem cells.

Stem cells are capable of renewing themselves for long periods of time. They can divide to yield very many cells. These cells can divide for months when stored in the right conditions. They are not specialized o any specific type of cells.

It is not known why;

  1. Why can embryonic stem cells proliferate for a year or more in the laboratory without differentiating, but most adult stem cells cannot.
  2.  What are the factors in living organisms that normally regulate stem cell proliferation and self-renewal?

Stem cells are not specialized. They cannot perform any specialized function. The unique property of stem cells is that they can proliferate to both stem cells and specialized cells. For example, embryonic stem cells give rise to the whole animal with all the organs. Bone marrow hematopoietic stem cells give rise to all the specialized blood cells. For stem cells to change to specialized cells, specific growth factors are supplied. These growth factors stimulate specific genes in the cell that make it specialize.

Note pluripotent cells can give rise to a number of specialized cells while totipotent stem cells can give rise to any cell type. Hematopoietic stem cells are pluripotent (plural potential) and embryonic stem cells are totipotent (total potential)

Induced pluripotent stem cells

 

Cellular reprograming

Somatic cells (adult cells) can be reprogrammed back to stem cells. This is called induced pluripotency.  Genetic reprograming is done by activating two major genes, Nanog or Oct4 . Once these genes are activated, a series of events occur and the cell goes back to stem cell.

This process is not as simple as it sounds. It requires carriers to transport the inducers that will target the specific genes. This can be done by use of vectors or chemicals

The most used vectors are viruses. The viruses are attached with a specific trigger. The virus attacks and integrates into the genome of the target cell. However, this process does not produce completely reprogramed cells. The other problem with use of viruses is continued expression of viral genes in the resulting cells. This can lead to cancerous activities. Lentinvirus produce less of this effect compared to retrovirus.

Chemicals are the best in inducing pluripotency. They have the advantage of not introducing any genetic materials into the host cell. However, no specific chemicals have been used to solely cause pluripotency.

Induced pluripotent stem cells

 

Potential medical uses for induced pluripotent cells.

Induced pluripotent cells have a great potential in treatment of most degenerative diseases. Degenerative diseases lead to loss of tissue. Any cell can therefore be reprogrammed and the stimulated to form the affected tissue. This is a very good approach since there is no graft rejection since the cell have been derived from the recipient. The recipient is still the donor. This has a major advantage since the patient does not have to use immunosuppresive drugs that can have serious side effects.

Sickle cell anemia is the result of a single point mutation in the hemoglobin gene, rendering red blood cells nonfunctional. In this proof-of-concept study, skin cells from the mouse model, which mimics the human condition, were first reprogrammed into induced pluripotent cells. The disease-causing mutation was subsequently fixed in induced pluripotent cells by gene targeting. The repaired cells were then coaxed into blood-forming cells. These now healthy stem cells were transplanted back into anemic mice, where they produced normal red blood cells and cured the disease. In principle, this approach could be applied to any disease in humans for which the underlying mutation is known, and that can be treated by cell transplantation. This conclusion is further supported by the phenotypic correction of hemophilia A.

Type 1 diabetes mellitus is caused by loss of pancreatic tissue due to attack by antibodies. New cells can be grown by induced pluripotent stem cells.

Other diseases like Alzheimer’s and Parkinson’s diseases can be treated by use of pluripotent stem cells.

Induced pluripotent stem cells

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    Dr Mathu

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