Stem Cells: In a Nutshell

Stem cells are cells which have the ability to differentiate into any type of tissue. We can make any kind of tissue such as an eye or a piece of bone, using these pluripotential stem cells. Thus if you have a damaged liver, just culture some stem cells and program them to grow into hepatic tissues. Replace your damaged liver with these cultured liver cells, you've got a fresh lease of life!

Ian Wilmut, professor and Head of the Department of Gene Expression and Development at the Roslin Institute near Edinburgh, Scotland, created the first clone derived from adult cells. He named it Dolly, after the celebrated singer Dolly Parton. The mechanism of its creation involved taking of cells from a sheep's udder and let it undergo some processes that involved specific nutritional starvation so that the skin cell forgot what it was and went back to its primitive undifferentiated stage. Normally, in a cell all the genetic components are there but the expression of them varies depending on the tissues involved. The genome of our eye (ophthalmic) cells are exactly the same as that of the liver cells: only difference is that some genes are silenced or switched off while some are on.

But the process involved is a tedious one. Now, Shinya Yamanaka of Kyoto University in Japan, have transformed mouse tail cells into embryonic stem cells using a much simpler technique. He used a retrovirus (which cause a type of leukemia and the dreaded disease AIDS and many others), and modified it so that its virulence was lost. He then introduced 4 regulator genes (OCT3/4, SOX2, KLF4, and c-MYC) in it, and let it mix with the skin cells taken from the facial skin of a 36-year-old woman in a petridish. Retroviruses, having the enzyme reverse transcriptase or RNA dependent DNA polymerase, has the ability to integrate the DNA into the dermal genome. There's a change of guard now. The dermal genome goes back in time as it becomes a stem cell as dictated by the 4 genes.

The advantage of this technique, apart from ease of manipulation, is the bypassing of moral and ethical dilemmas, that cropped up in the course of time. You no longer have to tinker with live embryos (as the US senate or the Papal office might have objections). One could grow organs for transplantation, perform clinical trials of drugs and even study cellular and molecular biological processes. Disease processes like Alzheimer's Dementia, Parkinson's Disease, other neurological diseases and cancer are some examples where cloning might throw some light upon. Attendant risks include formation of tumors due to the retroviral vector. In any case cloning is set to become commonplace anytime soon.

So, time to get ready for a doppleganger?

Last modified: 18 Oct 2009
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Stem Cell Therapy for Paraplegics May be Near

Our beloved superhero, the Superman, played by Christopher Reeve is no more. He fell from a horse and damaged his spinal cord in the process. As a result he got paralyzed and was restricted to the wheelchair. He could have recuperated if only the cut ends of the spinal cord were repaired. He was a staunch advocate of stem cell research.

It is now known that the spinal cord harbors stem cells, cells capable of differentiating into nerve cells (essentially all types of cells). So where have the stem cells gone? In adults, a molecule called netrin1, directs the stem cells away from an injury. Modifying the behavior of netrin1 may help in the recruitment of stem cells and their much needed transformation into neural elements. Simple grafting is impracticable, as cross connection may spell doom. Auriculotemporal (Frey syndrome) is one example where faulty neural connection gives rise to unpleasant symptoms. Moreover, the nerves and their synapses are so spatially oriented that correct axial positioning is next to impossible. For example, neurexins are molecules which are found in the synaptic terminals, which plays a pivotal role in the alignment of a synapse. They form connexions with neurexin receptors situated in the post synaptic neurons and thus guides the presynaptic terminal. The neural networking is indescribably complex.

Finding a solution through netrin1 may be of immense benefit not only in spinal cord injury but also in diseases like cerebrovascular accident (CVA/ Stroke).

Again, the brain-computer interface robots being developed by researchers, based on 'thought controlled devices' are becoming a reality. These humanoids may one day enable paraplegics to be able to move freely in their wheel chairs, command computers or TV stations remotely and in other day to day activities.

Hayflick limit, Telomere and Aging

We keep our pens capped so that the pen tips don't get damaged and the ink doesn't dry. Similarly, the DNA in the chromosomal ends are 'capped' by protective molecules, called the telomeres. Telomeres consist of about 1000 repeats of 'TTAGGG" sequence, where T stands for Thymine, A for Adenine and G for Guanine. All these are nitrogen containing molecules (nitrogenous bases).

During replication, the double helical DNA molecule is first unwound by an enzyme called helicase, it is then split by another enzyme, gyrase (=type 2 topoisomerase: it does it by un-twisting the DNA helix in the opposite direction, by introducing negative supercoils, and then makes a nick in one DNA strand, so that it can be copied), and only after all this can DNA polymerase copy the DNA template.

But after each replication, some of this telomere, the so called 'non functional strand' of DNA, is lost. This occurs, since DNA polymerase can not copy one end of the DNA (the 5' end). Thus it has been seen that after about 50 cell divisions, the cell dies (Hayflick limit). When the telomeres are shortened up to a certain limit, the cell sends a signal to p53 protein (known as the guardian of the genome), and the cell then stops dividing and goes into 'replicative senescence'. Stem cells, germ cells and cancerous cells can bypass this limit by the help of telomerase, an enzyme capable of replenishing lost telomeres. Telomerase is actually a reverse transcriptase (normally DNA generates RNA and this process is called transcription. When RNA generates DNA it is thus reverse transcription. In AIDS, another reverse transcriptase wrecks havoc). Telomerase (hTERT= human telomerase reverse transcriptase) and a RNA template (template=dice, just like webpage templates) is enough for telomere reconstruction. However, the idea of restoring telomerase for cellular 'immortality' is not assuring enough as immortality in cells other than stem cells or germ cells means malignancy.

Some substances like alpha hydroxy acids (AHA) glycolic acids, when applied on the skin (face) promotes cell division, thus prompting the growth of new cells, the facial skin gets a cosmetic lift; but due to enhanced cell division, after a certain stage, cells approach the Hayflick limit, and the skin gets aged and wrinkled.

Thus telomerase manipulation should be cautiously weighted against its accompanying risks.

Related article: Aging: From a General and Evolutionary Perspective
Aging, Mitochondria and Free Radicals