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The pluripotent promise
Dr Anjali Shukla | Thursday, September 27, 2007, 08:00 Hrs  [IST]

A stem cell is a cell, whose job in the body is not yet determined. Every single cell in the body 'stems' from this type of cell and hence the name stem cell. Stem cells are primal cells present in all multicellular organisms that retain the ability to develop into many different cell types in the body.

These cells serve as a sort of repair system for the body, as they can theoretically divide without limit to replenish other cells as long as the person or animal is alive. When a stem cell divides, each new cell has the potential to either remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, red blood cell or brain cell. Owing to these characteristics, stem cells are now widely used in medical therapies.

All stem cells - regardless of their source - have three unique properties. They are:
■ Stem cells are capable of dividing and renewing themselves for long periods
■ Stem cells are unspecialized
■ Stem cells can give rise to specialized cell types

Cell character
Unlike muscle cells, blood cells and nerve cells, which do not normally replicate themselves, stem cells may replicate many times. A starting population of stem cells that proliferates for many months in the laboratory can yield millions of cells. If the resulting cells continue to be unspecialized, like the parent stem cells, the cells are said to be capable of long-term self-renewal.

The scientists have great interest in understanding the specific factors and conditions that allow stem cells to remain unspecialized. It took almost two decades to learn how to grow human embryonic stem cells in the laboratory following the development of conditions for growing mouse stem cells. So, the target is to understand the signals in a mature organism that cause a stem cell to proliferate and remain unspecialized until the cells are needed for repair of a specific tissue.

If stem cells are unspecialized, then what is so special about them? Stem cells do not have any tissue-specific structures that allow it to perform specialized functions. However, unspecialized stem cells can give rise to specialized cells, including heart muscle cells, blood cells and nerve cells.

Forming specialized cells
Like actors awaiting a call for dates, stem cells wait for signals to tell them what to become. When unspecialized stem cells give rise to specialized cells, the process is called differentiation. There are signals inside and outside cells that trigger stem cell differentiation. The internal signals are controlled by a cell's genes. The external signals for cell differentiation include chemicals secreted by other cells, physical contact with neighbouring cells and certain molecules in the microenvironment.

There are many questions regarding stem cell differentiation. For example, are the internal and external signals for cell differentiation similar for all kinds of stem cells? Can specific set of signals be identified that promote differentiation into specific cell types? The answers of these questions may lead researchers to find new ways of controlling stem cell differentiation in the laboratory, thereby growing cells or tissues that can be used for specific purposes, including cell-based therapies.

Scientists are trying to understand two fundamental properties of stem cells that relate to their long-term self-renewal. They are:
■ Why can embryonic stem cells proliferate for a year or more in the laboratory without differentiating, but most adult stem cells cannot?
■ What are the factors in living organisms that necessarily regulate stem-cell proliferation and self-renewal?

If the answers to these questions are discovered, it becomes possible to understand how cell proliferation is regulated during normal embryonic development or during the abnormal cell division that leads to cancer.

Embryonic stem cells
Embryonic stem cells are derived from embryos. Specifically, embryonic stem cells are derived from embryos that develop from eggs that have been fertilized in vitro and then donated for research purposes with informed consent of the donors. The embryos from which human embryonic stem cells are derived are typically four to five days old and are a hollow microscopic ball of cells called the blastocyst. The blastocyst includes three structures: trophoblast, which is the layer of cells that surrounds blastocyst; blastocoel, a hollow cavity inside the blastocyst and inner cell mass, which is a group of approximately 30 cells at one end of the blastocoel.

To generate cultures of specific types of differentiated cells (heart muscle cells, blood cells or nerve cells), scientists try to control the differentiation of embryonic stem cells. They change the chemical composition of the culture medium, alter the surface of the culture dish or modify the cells by inserting specific genes.

If scientists can direct the differentiation of embryonic stem cells into specific cell types, they may be able to use the resulting differentiated cells to treat certain diseases at some point in the future. These diseases might include parkinson's disease, diabetes, traumatic spinal cord injury, purkinje cell degeneration, duchenne's muscular dystrophy, heart disease and vision and hearing loss.

Adult stem cells
An adult stem cell is an undifferentiated cell found among differentiated cells in a tissue or organ. This type of cell can renew itself and differentiate to yield the major specialized cell types of the tissue or organ. The primary role of adult stem cells in a living organism is to maintain and repair the tissue in which they are found. Researchers are really excited to find adult stem cells in many more tissues than they once thought possible. This finding raises a question that whether adult stem cells could be used for transplants. In fact, adult blood forming stem cells from bone marrow have been used in transplants for 30 years.

In the 1960s, researchers discovered that the bone marrow contains at least two kinds of stem cells. One population, called hematopoietic stem cells, forms all the types of blood cells in the body. A second population, called bone marrow stromal cells, was discovered a few years later. Stromal cells are a mixed cell population that generates bone cartilage, fat and fibrous connective tissue.

Potential uses of human stem cells
There are many ways to use human stem cells in basic and clinical research. Along with this come many technical hurdles between the promise of stem cells and the realization of their uses, which will only be overcome by continual intensive stem cell research.

Studies of human embryonic stem cells may yield information about the complex events that occur during human development. A primary goal of this work is to identify how undifferentiated stem cells become differentiated. Turning genes on and off is central to this process. Some of the most health conditions, such as cancer and birth defects, are due to abnormal cell division and differentiation. By understanding the genetic and molecular controls of these processes, a good amount of information about how such diseases arise can be received. This may also suggest new strategies for therapy. A significant hurdle to this and other uses of stem cells is that scientists do not yet fully understand the signals that turn specific genes on and off to influence the differentiation of the stem cell.

Human stem cells could also be used to test new drugs. For instance, new medications could be tested for safety on differentiated cells generated from human pluripotent cell lines. Cancer cell lines are used to screen potential anti-tumour drugs. But, the availability of pluripotent stem cells would allow drug testing in a wider range of cell types. However, to screen drugs effectively, the conditions must be identical when comparing different drugs. Therefore, scientists will have to be able to precisely control the differentiation of stem cells into a specific cell type on which drugs will be tested. Of course, the most important potential application of human stem cells is the generation of cells and tissues that could be used for cell-based therapies. These days, donated organs and tissues are often used to replace ailing or destroyed tissue, but the need for transplantable tissues and organs far outweighs the available supply.

The future
Researchers are working to design stem cell therapies that are more effective, and reduce the invasiveness and risk to patients. Currently, stem cell therapies usually rely on cells that are donated by another person. This raises the possibility of donor cell rejection by the patient's immune system. In the future, it may be possible for a person to use a sample of his or her own stem cells to regenerate tissue, which would reduce or even eliminate the danger of rejection. But how might this be done? The possibilities are:
■ Collecting healthy adult stem cells from a patient and manipulating them in the laboratory to create new tissues. The tissue would be re-transplanted back into the patient's body, where it would work to restore a lost function
■ Therapeutic cloning might enable the creation of embryonic stem cells that are genetically identical to the patient
■ Scientists might design a drug that would direct a certain type of stem cell to restore a lost function inside the patient's body. This approach would eliminate the need for invasive surgical procedures to harvest and transplant stem cells

Stem cell banking
India's first private cord blood stem cell bank, 'Lifecell' was launched in Chennai in 2004, a joint venture between Asia Cryo Cell Pvt Ltd and Florida-based Cryo-Cell International. The umbilical cord, connecting the foetus with the mother is cut at the time of delivery and discarded.

Cord blood (the remaining blood in the umbilical cord) is full of 'stem cells', which is the origin of the body's immune and blood system. Cord stem cell preservation consists of collecting the 'leftover' umbilical cord blood from the placenta and umbilical cord after the baby is delivered and the cord is cut. This blood is sent to a bank where it is processed and preserved by freezing them in liquid nitrogen at a temperature of - 195°C.

Researchers opine that collecting and preserving a baby's cord blood stem cells would be a security blanket for the baby and his family members. In fact, it is estimated that the probability of a need for cord blood stem cells arising within a family is as high as 1/1,500.

Collection of these priceless stem cells is a totally safe procedure and do not pose any threat to the health of either mother or newborn. It is usually performed by inserting a needle into the umbilical cord and drawing-off blood following delivery of the baby. The blood is collected in a special UCB blood bag. It is totally painless and non-invasive procedure.

The sample is placed inside a temperature-controlled container to preserve sample's viability until it reaches the laboratory. After they have reached the destined place, the stem cells will be processed, then cryogenically frozen and stored.

These stem cells will be 'on deposit' for the child, or indeed, any member of the family, who may need them in the future. Using one's own cells eliminate the worry of rejection or the need to find a compatible donor should the need ever arises.

The need to establish clean room facilities to handle stem cells has been realized and a number of facilities have been created. These facilities have been established mainly in hospital set up because hospitals are the main source for providing these cells and no facilities were available to handle stem cells in their set up.

(The author is with Accure Labs Pvt Ltd, Noida)

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