THE CURE WITHIN THE CELL

So what are stem cells?
Stem cells are the basic building blocks of the body, which begin developing as soon as fertilisation occurs. “They are the first cell cluster that comprises the embryo and thereafter divide, develop and change to form the complete human body,” explains Dr K. Ghosh, Director, National Institute of Haematology, Mumbai.
This change of form by the blank cells into various tissues — a process known as differentiation — is one of the aspects that make stem cells so important. No other types of cells have this capability. “The other important part is their repairing capacity. Not just in the embryo, in the adult body too, every tissue and every organ has its own stem cell bank. Though normally dormant, these are activated as soon as repair is needed — cuts and fractures are healed and blood cells are replenished,” he adds.
Harnessing this reform and repair capacity of stem cells to treat the degeneration of tissues and organs and thereby cure various diseases is what stem cell treatment is all about. Though much of them are yet to be realised, the applications can be endless: Blood to cure anaemia and leukemia; brain for dementia and Parkinsons; eye for retinal and corneal regeneration; heart for strokes and malformations; pancreas for diabetes and bone for fractures and implants.
The basic process sounds simple enough: inject the stem cells locally — or in the bloodstream, in which case they travel to the target area — and they adopt the characteristics of the surrounding cells to repair the degenerated portion.
As of now, stem cells injected are harvested from the patient’s own body, thus skipping the rejection factor and the embryonic cell controversy. But because stem cells from any part of the body can be made to develop into any type of tissue — this special quality being called “plasticity” — it expands the scope and potential of the research.
“The practical difficulty, of course, is separating the stem cells from mature tissues like muscles or heart tissues,” points out Dr Ghosh, “which is why in most cases, haematopoietic stem cells (blank multipotent cells) are sourced from bone marrow”.
But clinically, doctors say, there is a chance of better results if instead of using blank cells, the differentiation is done in the lab and the cells are then used. Roughly, this would mean separating the stem cells, keeping them with the cells of the target organ in a micro environment to help them adopt the characteristics of the wanted tissue and then injecting the processed cells back into the body. The procedure is already being researched and comes under the broad category of “developing cell lines”.
This is where the ethical issue crops up, for between the stem cells harvested from adult organs and the stem cells cultured from embryos, the latter, being young cells, always have the edge functionally.
And this is also why, though over 20 countries are into stem cell research, the ones in the Asian block that do not have a predominantly Christian population, may beat the West.

Does that mean that India, as of now, is on a strong wicket?
Not really, it seems. “But we began early enough,” says Ghosh. “Way back in 1977-78, Dr V Kochupillai extracted stem cells from foetal liver to treat aplastic anaemia, a type of leukemia, at the All India Institute of Medical Sciences. This was even published in the journal Thymus. Unfortunately, we keep tabs more on the work of scientists abroad and pay little attention to the achievements of our own.”
As of today, at least 20 facilities in India are working on stem cells — pure research and clinical application. Besides, there are private enterprises like Lifecell, Cryobanks, Manipal Institute and Reliance Life Sciences, which are into storage of umbilical cord cells and development of cell lines for research and clinical purposes. The Apollo Group also intends to get into the field soon.
A substantial part of the pure research is being carried out at the National Centre of Cell Sciences, Pune, where scientists are still testing the potential of the stem cells in laboratory conditions. Separation of cells from organs, the best means of culturing them, testing methods of differentiation so stem cells from any area can be converted into any tissue and checking out the clinical possibilities through animal trials are the primary area of work, says Scientist Dr R.R. Bhonde.
The other field is to check out the methods of storage and its time frame — currently in liquid nitrogen at a temperature of minus 196 degrees Celsius — and theoretically, they can be kept for decades.
The best repositories of stem cells have already been identified: bone marrow, umbilical cord, placenta, amniotic fluid and even adipose tissue, or fat. In fact, adipose tissue has vast quantities of stem cells, which is probably why fat proliferates so easily. “One may even say this is one area in which fat is fit,” chuckles Dr Bhonde.
Does this mean that soon stem cells are being separated from fat and overweight people can actually benefit without processes like cord blood preservation or bone marrow withdrawal?
There have been some reports of this being tried in Ahmedabad. But unfortunately, shifting work from labs to hospitals is no mean task. “There is a huge gap between what the basic scientists find and what clinicians can use of it,” says Bhonde, “replicating in-vitro work (done outside the body) in the body itself is not easy.”
There’s also the question of standardisation of clinical parameters like how many cells to inject (this is in lakhs and is measured in cubic centimeters). After all of that, if a certain process is found successful, even in animal trials, there’s the question of evading possibilities like infection, since harvesting and culture of cells exposes them to air and foreign surfaces and therefore contamination.

Eye, heart and nerves
So what of the places that are actually doing some clinical work? Most of the efforts in this direction are on at the All India Institute of Medical Sciences in New Delhi. And among the more streamlined efforts, the most successful is perhaps the LV Prasad Eye Institute, Hyderabad, which has perfected the method of regenerating corneal stem cells.
“Mostly we treat cases of chemical burns in the cornea, in which limbal stem cells from the good (or the better) eye is harvested, cultured and planted in the affected eye,” says Dr Geeta K. Vemuganti, Head, Ophthalmic Pathology Service and Stem Cell Laboratory of the institute. Over the last seven years, the institute has conducted 550 such procedures.
The corneal surgery is also done at AIIMS, but the institute’s ophthalmology department is trying to break new ground with its work on retinal degeneration, says Prof R.V. Azad. While initial results are good, it falls far short of expectation. The institute is now trying to develop a cell line and inject those cells instead of using stem cells directly.
But the most interesting results that it has received are undoubtedly in cardiology, which has already attracted a lot of attention.
“The other fields of work include neurology and orthopaedics, where scientists are trying to heal the breach fully in case of fractures where metal rods and metal screws have to be inserted,” says Sujata Mohanty, in charge of the Stem Cell facility at AIIMS. Another area where doctors have met with some success is paediatrics. Stem cells have proved particularly useful in cases of spina bifida.
If that was not enough, stem cell research even might breach the final barrier: cancer.
Being the basic building blocks of the body, stem cells even have a role to play in tumours, which are just unnatural proliferation of cells, explains Dr Sharmila Bapat, Scientist, who is currently working on ovarian cancer and stem cells in the Cancer Research Centre of NICS, Pune. “In case of cancerous tumours, research had found that stem cells cause growth even after the cancerous tissues are destroyed through chemotherapy and radiation, causing a relapse.” Scientists are now trying to isolate and study these cancerous stem cells and develop a new generation of drugs to target them, says Bapat, whose book Cancer Stem Cells is due to be published in June.
So how does the future look? Will stem cell therapy bear out its initial prognosis?
“Treatment with haemopoietic stem cells has met with considerable success and we have partially fulfilled our small dreams, patching up corneas and bones,” says Dr Ghosh. “But the real challenge lies in actually harnessing the potential of embryonic stem cells to regenerate organs like liver and kidney. While this has been done in a laboratory or two abroad, one must remember that a lab is a very controlled environment, which is nowhere near the real thing. Lab success is no guarantee that the same will be automatically replicated in the body.”
Dr Bhonde agrees. “As of now, the matter is swinging between hope and hype, with the hype predominating. But we may have a clearer picture in 10 years’ time. All being well, chances are someday, organ transplants may just be redundant.”