Stem cells have always fascinated biologists for their potential to unleash completely new kinds of treatment in the field of regenerative medicine. Ever since human embryonic stem cells (hESCs) were first isolated in 1997 by researchers at the Johns Hopkins Medical Institutions, stem cells have hogged the limelight in media circles and among the heavyweights of research and the pharmaceuticals industry for their remarkable ability to do hitherto unimaginable things.
Stem cells are the fundamental progenitor cells from which all human organs develop. All stem cells, regardless of their source, have three unique properties: they are capable of dividing and renewing themselves for long periods; they are unspecialized; and they can give rise to specialized cell types. There are two primary sources of stem cells, human embryonic stem cells (hESCs) derived from the embryo and the adult stem cells (ASCs), which can be obtained from peripheral blood or even human fat. The primary role of ASCs in a living organism is to maintain and repair the tissue in which they are found.
When an egg cell is first fertilized and starts to replicate, the early cells are uniform and totally undifferentiated. These are the embryonic stem cells (ESCs). As they continue to divide, they differentiate into nerve, skin, bone, and all the other specialized cells that make up the body.
These specialized cells begin to produce specific molecular factors, express specific receptors and membrane proteins, form extra cellular matrix, and signal to surrounding cells to form discrete organs. Finally, they begin to function as part of mature tissues--pancreatic islet cells produce insulin and respond to feedback; neurons sprout axons and connect with other neurons to form the brain, to name a few.
It had been assumed that ASCs could differentiate only into the same tissue type from which they came--in other words, hematopoietic stem cells could become only blood cells, but not nerve or kidney cells, while mesenchymal stem cells could become cartilage, bone, tendon and ligaments, muscle, skin, fat, and nerve cells. However, there is now some evidence that some ASCs may be totipotent, or able to become any of the cell types in the body. This is known as transdifferentiation or plasticity.
Unlike hESCs, which appear to be able to divide an unlimited number of times without senescing or differentiating, ASCs may not have an indefinite lifespan. ASCs are rare in mature tissues and methods for expanding their numbers in cell culture have not yet been worked out. This is an important distinction, as large numbers of cells are needed for stem cell replacement therapies.
Stem-cell researchers are trying to understand two fundamental properties of stem cells that relate to their long-term self-renewal: 1) why can embryonic stem cells proliferate for a year or more in the laboratory without differentiating, but most adult stem cells cannot; and 2) what are the factors in living organisms that normally regulate stem cell proliferation and self-renewal?
Thus, one of the major challenges stem-cell scientists have faced has been to decipher the signals that cause a stem cell population to proliferate but remain unspecialized, whether in an embryo or in adult tissues where they are kept in reserve for repair. Progress on this front has been rapid in the last few years, however. Another major stumbling block to ESC therapeutics is that, even though the stem cells cultured from embryos are pluripotent, they still express foreign antigens, which raises problems of immune rejection.
Use of hESCs in research has generated much debate and considerable political conflict because hESCs are obtained either from discarded human embryos or through the often misunderstood method called 'therapeutic cloning.' Therapeutic cloning is the creation of a cloned embryo using a patient's own DNA for the sole purpose of collecting stem cells from that embryo. Regulations in the United States forbid public funding for research on hESCs, with the exception of cells derived from about 12 existing stem cell lines. Additional new hESC lines have been developed by a few companies and researchers not relying on public funds, but there still are not enough to go around.
In spite of the above-mentioned challenges, research in stem cells is pursued vigorously. More and more venture capital is flowing into research aimed at further refining stem cell technology.
As the population in the developed countries is ageing, more people will experience failure of one or more crucial organs, and there simply aren't enough donor organs available to meet demand. Technology based on stem cells promises to fill this void by providing a cheaper and potentially less harmful route to repair damaged or diseased tissue either by harvesting the patients own cells or employing embryonic stem cells. Numerous labs are exploring the use of stem cells for gene therapy.
The hope is that therapeutic genes might be inserted into stem cells taken from patients, after which the cells would be expanded to large numbers and reinjected into the patient. They could then be induced to become whatever cell type is needed to best deliver the therapeutic genes. Many researchers and companies are extremely motivated to develop gene therapy into a viable technology.
A major focus of research today is to use stem cells to generate replacement tissues for treating neurological diseases. Spinal cord injury, multiple sclerosis, Parkinson's disease, and Alzheimer's disease are among those diseases for which the concept of replacing destroyed or dysfunctional cells in the brain or spinal cord is a practical goal. Stem cells are also looking quite promising for bone and cartilage repair.
The necessary knowledge and understanding regarding stem cells is coming. Some diseases such as haemophilia, cystic fibrosis, cardiovascular disease, and cancer will almost certainly be more amenable to treatment with gene therapy than other diseases like Alzheimer's which affects the entire brain.
In summary, stem cells hold enormous potential to solve some of the most difficult medical problems of our time. A great deal of work remains to be done, however, before they become commercially viable.
- S Ravi Shankar is Research Analyst - Technical Insights Group, Frost & Sullivan. The author can be reached through : sdedhia@frost.com