Understanding Regenerative Medicine
By Arjuwan Lakkdawala
Ink in the Internet
It started in the 50s with the first bone marrow transplant, and stem cell research has taken off with promising results and astonishing insights into cells and genes, and the remarkable way in which human and animal bodies function on the cellular level.
Regenerative medicine is being tested and explored in the treatment of several diseases including cancer and heart disease, two of the leading causes of deaths world wide, researchers also have hopes of finding treatments through it and learning about how Alzheimer's diseases can be treated and its degenerative effects. This is of significance considering the rise of Alzheimer's disease in the past twenty years. (I suspect mobile phones maybe the culprit, read my previous article.)
So what are stem cells exactly and how are they being used in regenerative medicine?
There are many types of function specific cells in the body, the stem cells being tested and used are basically of two main types. One is the embryonic stem cells that are taken from an human embryo which is 3 to 5 days old and has 150 cells, and is from an egg fertilised in vitro fertilisation clinic and has not been implanted in the uterus. It is without a doubt controversial as it raises questions of the ethics of this particular research.
Stem cells can also be found in umbilical cord blood, and the amniotic fluid, which fills the sac surrounding the fetus in the womb.
Women giving birth in hospitals should be notified if the umbilical cord blood is taken for stem cell collection.
These stem cells have the capability to differentiate (turn into) almost any function specific cell in the human body, making them highly favourable for testing and studying how they mature, they can also be frozen to be stored without getting damaged, and they are stable and durable.
Stem cells with the capability to differentiate are called pluripotent cells.
The other type are adult stem cells that have already differentiated into function specific cells, these are found in the bone marrow and fat in the body. While at first it was thought that their capabilities were limited in treatment or testing, scientists are discovering that adult stem cells are useful in many ways and are easier to match to a patient than embryonic stem cells. Because the body's immune system is most likely to attack embryonic stem cells from a donor than its own adult stem cells that have been reprogrammed for treatment.
However, adult stem cells could have defects due to environmental hazards or toxicity.
In both main stem cell types it is tools of reprogramming that is being developed.
In 2006, the Nobel Prize-winning scientist Shinya Yamanaka and his team, at Kyoto University in Japan, discovered how to revert adult stem cells into embryonic stem cell like state.
This is called Induced Pluripotent Stem Cells or iPSC.
The genes that define an embryonic stem cell are there in every cell in the body but they are turned off. Yamanaka pioneered the technique to turn on those genes in adult stem cells. He did it by injecting molecules in the adult stem cells with the instructions to turn on the embryonic stem cell genes, and by this changing the identity of the adult function specific stem cell into an embryonic like stem cell.
The instructions for gene reprogramming are in proteins or chemicals that mimic proteins that have been selected to alter the identity of the stem cells into the function specific cells required for potential treatment or testing.
For example, if a patient suffering from heart disease is injected with healthy stem cells that have been turned into heart cells, they could help treat the heart.
Or in the case of testing, new drugs can be tested on stem cells that have been differentiated into the cell type in the body targeted by the drugs. Scientists can study if the drug is effective at treating the cells or causes adverse affects. This is of course much better than testing the drugs on living humans or even animals. Animals have suffered so much because of lab testing. I hope stem cells would be a sufficient alternative to animal testing.
The other way in which stem cell research is very useful is that through it researchers and scientists can study cells otherwise inaccessible. Like for example neurons in the brain.
Stem cells can be differented into neuron like cells, they won't be exactly the same but very close proxies.
Studying stem cells that have been successfully turned into different types of cells of the body in a culture petri dish allows scientists to much easily observe the onset of diseases and test possible treatments. Stem cells are also being considered as alternatives to organ transplant, and tests are ongoing in this context.
The human body has regenerative abilities like the skin healing after wounds or hair growing back. But it is the liver that is most astonishing as it has cells that can regenerate while other organs in the body don't. Scientist are studying why this is.
However, regeneration in humans is nothing compared to some species in the animal kingdom. Like for example worms, lizards, salamanders, jellyfish.
Researchers at Whitehead Institute are studying regeneration, and Professor Peter Reddien, is especially focused on a type of flat worm that has remarkable regeneration capabilities. The worm planarian can regrow its whole body even when it has been cut into pieces. Each piece will grow into a whole new worm.
Another worm was introduced for studying and testing by Professor Mansi Srivastav, the model worm suitable for testing and experiments is the three-banded panther worm. Both worm species have regenerative capabilities and studies have shown that neoblasts (worm stem cells) in the muscles of the worms are guided by Position Control Genes PCGs into regenerating the whole worm from each piece.
Scientists are developing new techniques of the process of actually introducing proteins or chemicals acting like proteins into the cell membrane of the stem cells or adult stem cells to be reprogrammed.
The percentage of successful reprogramming so far is not high. Previously a virus was used to inject transcription instruction factors into stem cells. But this method was imperfect.
Newer methods include using a plasmid, a circular DNA construct to enter the stem cell membrane with the transcription instructions, after the cell has been zapped with an electric current that makes a temporary hole in it.
While this method of using electricity to change genes is used in labs, a recent study from the University of Nagoya in Japan, studied electric eels that were used to zap zebra fish, using an electric field, they found that the genes of the fish had changed.
The study was published in the journal PeerJ-Life Environment.
"Electric eels and other organism that generate electricity. Could affect genetic modification in nature," said Atsuo Lida, professor and author on the study.
We don't know if the 860 volts discharged from eels in the amazon river has contributed to gene transfer between species but it's a possibility.
The human genome has ca. 20,000 genes that construct proteins. Genes and proteins are the building blocks of life.
Therefore stem cell reprogramming is wholly based on using proteins or chemicals mimicking proteins to alter cells into function specific cell types.
However, the creation of new genes is just as much a mystery as the start of biological life.
A recent discovery by the University of Helsinki in Finland, has a possible answer to the mystery of the mechanism behind the making of new genes. The classical genes that make proteins have regulatory genes, and as the university was studying errors in DNA replication they found that a mutation event can give rise to the very tiny sort of sub-genes from which perhaps other larger genes are made.
Arjuwan Lakkdawala is an author and independent science researcher.
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Copyright ©️ Arjuwan Lakkdawala 2024
Sources:
SciTech Daily - Palindromic Puzzles Solved: the Hidden Mechanism of Gene Creation, University of Helsinki
National Library of Medicine - Induced Pluripotent Stem Cells: Reprogramming Platforms and Applications in Cell Replacement Therapy, Akram Al Abbar, Stewart Ching Ngai, Nadine Nograles, Suleiman Yusuf Alhaji, Syahril Abdullah
Electric Eel Zaps can Change Fish DNA - Popular Mechanics, Tim NewComb
ISCRM - What is Cell Reprogramming
The Science of Self-Repair: Regeneration Research at Whitehead Institute by Greta Friar
Mayo Clinic Staff - Stem Cells: What are they and what do they do
