Revolutionary Medicine: "Say Hello to Stem Cells!!"
Author: Silvan S. Prayogo, BSc. Biochem & Mol. Bio, MSc. Biotechnology
Last updated: 27 July 2007.

James, a 21 years old college student severed his spinal cord in a car accident. He was paralyzed from his neck down. In a hospital, a team of medical doctors and scientists took a blood sample from him to isolate a group of "special cells" in his blood. The scientists manipulated the cells in a laboratory before transplanting them onto the site of James' damaged spinal cord. A few months later, James can play soccer, do wall climbing, and function normally as if the accident never happened. This story occurs sometimes in the future, the "special cells" are stem cells, and the medical procedure that cures James is called stem cells transplantation. Today, although the exact tissue repair mechanism by stem cells is unknown, many studies indicate the potential of stem cells to cure various degenerative diseases. Millions of US dollars are spent on stem cells research all over the world. However, at the same time, stem cells also receive heavy scrutiny from many communities such as religious, politic, and even scientists. What are stem cells? Why do they cause so much controversy? Why do biotechnology companies and nations race to get their hands on stem cells-based discoveries?

Stem cells are unspecialized and undifferentiated cells that have a capability to proliferate (multiply in number) by cell division and differentiate (transform) into specialized cells in the presence of certain favorable stimulus. In terms of differentiation, a stem cell is analogous to a student who has just graduated from a high school. She has all the basic knowledge to choose any career path. She may choose to be a musician, a doctor, an engineer, and many more. Since she grew up in a community of medical doctors (e.g. her parents and neighbors are doctors and she lives near a hospital), therefore, she is stimulated to choose a career in medicine. If her study in college goes smoothly (e.g. no financial or health problem, etc), then, she eventually becomes a certified medical doctor (a person specialized in medicine). By the way, she cannot split her self to proliferate like cells. I have to find another analogy to explain that some other time.

So, have you begun to guess the prospect of stem cells in medicine? The prospect of stem cells is in regenerative medicine. Stem cells can be manipulated to become any cells in your body. Therefore, stem cells can replace any damaged cell and repair damaged tissues or organs that would otherwise be difficult or impossible to heal such as a spinal cord injury, brain damage due to stroke, or cardiac muscle damage due to a heart attack (myocardial infarction). Stem cells research also aims to regenerate a whole new organ such as a liver or a heart so that patients for organ transplant do not have to wait too long to find a perfect match organ donor because the organ would be generated from the patients' own stem cells. Unfortunately, scientists are still a long way from creating a whole new organ. Current stem cells therapeutic applications are limited to diseases that can be treated by injection of single cells type. For example, stem cells therapy to cure patients who suffer diabetes type-1. Diabetes type-1 is caused by lack of functional beta cells that secret insulin. Since beta cells are the only cell type responsible for diabetes type-1, therefore, stem cells would be a suitable therapy to generate new functional beta cells (Biotech International, November 2004).

Stem Cells Classification

Stem cells are classified into four types according to their differentiation potency(www.stemcellresearchfoundation.org). Stem cells that maintain their potency to differentiate into any kinds of cells and placenta are known as totipotent stem cells. A zygote (an egg that has been fertilized by a sperm) is an example of a totipotent cell because it has a total potential to develop into a fetus (Lim, 2002, pg. 186). Four days after fertilization, another kind of stem cells is formed and classified as pluripotent stem cells. These cells can develop (differentiate) into various kinds of cells in the body (e.g. heart, liver, and many more) except placenta. Embryonic stem cells (ES cells) are classified as pluripotent stem cells. The descendents of pluripotent stem cells are multipotent stem cells. These cells have a limited differentiation potential. For example, hematopoietic stem cells (precursor of blood cells) in bone marrow and umbilical cord blood usually only differentiate into various kinds of blood cells such as erythrocytes, leucocytes, and platelets. Neural stem cells also belong to this group because they usually only differentiate into nerve cells and glia cells. Lastly, stem cells that only differentiate into one cell type are classified as progenitor cells (unipotent stem cells). An example of progenitor cells would be erythroid progenitor cells because they only differentiate into erythrocyte (red blood cells).

Embryonic vs. Adult Stem Cells

Stem cells are classified as Embryonic Stem Cells (ES cells) and Adult Stem Cells according to the source where stem cells are collected. ES cells are found in the inner cell mass of a blastocyst (a four days old embryo) as shown in the following figure. Human ES (hES) cells for research are usually obtained from unused In Vitro Fertilization (IVF) embryos. More than one embryo are created in an IVF procedure to increase the likelihood of a successful pregnancy. However, only one would be used at a time to grow into a baby. Once a successful pregnancy is achieved, the remaining embryos would be frozen and stored. The biological parents (the owners) have a choice to either use one or some of the embryos to conceive another baby, or to donate the embryos to other surrogate mothers who wish for pregnancy, or to throw (destroy) them away, or to donate them for scientific research (e.g. hES cells research). The last three choices would require an informed consent from the biological parents.

Human ES cells research usually involve cloning of human embryos to harvest more identical hES cells. Cloning of human embryos for therapeutic purposes is referred as therapeutic cloning. Human embryonic stem cells are pluripotent and easier to isolate and grow than  adult stem cells  (Schmid, 2003, pg. 128). Therefore, theoretically, hES cells is an excellent candidate for regenerative medicine. However, human ES cells research is controversial because a human embryo would not  develop into a baby once the stem cells are harvested (i.e. the embryo is ruined). Some people regard an embryo at any stage is a living human being, therefore, a deliberate destruction of a human embryo for whatever reasons (research or therapeutic) is a murder. As a result of this moral and ethical dilemma, progress in human ES cells research is slow.  

By contrast, adult stem cells are harvested from an adult tissue such as from aborted fetuses, umbilical cord blood, placenta, and from parts of your bodies (e.g. bone marrow, fat, peripheral blood, nasal cavity, etc). Therefore, it does not raise ethical controversy and adult stem cells research progresses more rapidly than hES cells research. Unfortunately, adult stem cells are multipotent, limited in numbers, difficult to isolate and grow, and have a higher risk to contain DNA mutations because they come from mature tissues that might have been exposed to mutagens (agents that cause DNA mutation). Despite these difficulties, studies and clinical trials have shown that adult stem cells can be manipulated to be pluripotent. Adult stem cells therapies have been performed many times such as umbilical cord blood stem cells transplantation to cure thalassaemia, peripheral blood or bone marrow stem cells transplantation to treat leukemia, and bone marrow stem cells transplantation to repair myocardial infarction.

One of the main challenges in a stem cells research is to control the stem cells differentiation. How to ensure that a stem cell would differentiate into the desired specialized cell? You do not want the stem cells that supposedly replace your damaged heart muscle cells turn into skin cells. The risk of an uncontrollable differentiation is higher in embryonic stem cells due to their pluripotency (www.stemcellresearchfoundation.org and www.thehill.com, 14 September 2005). Embryonic stem cells may differentiate into tumor or cancer cells because they can easily proliferate indefinitely.

Stem cells is one of current hot biotechnology topics. Stem cells show promising solution for debilitating degenerative diseases such as Alzheimer, Parkinson, myocardial infarction, and many more. People are inpatients for their governments to ease and legalize stem cells-based therapies. However, how much do people know about stem cells? Further studies on stem cells are still required. Could stem cells be the next magic bullet after penicillin in the 1950s? How long should we wait for scientists to unanimously declare that a stem cells therapy is safe and effective? Stay tune for more stem cells in the next articles.

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  References:

1. Lim, H. A. (2002),”Genetically Yours-Bioinforming, Biopharming, Biofarming”. World Scientific Co. Pte. Ltd, Singapore. Pg. 186, 189-193.

2. Schmid, R. D. (2003),”Pocket Guide to Biotechnology and Genetic Engineering”. Wiley-Vch Verlag GmbH & Co. Germany. Pg 128.

3. Urbach, A. (November 2004),”The Potential of Human Embryonic Stem Cells.” Biotech International. Vol. 16. No. 6. Pg. 8-11.

4. Smith, C. (14 September 2005). Stem cells of hope, not hype, are curing people [online]. The Hill. Available from: http://www.thehill.com/thehill/export/TheHill/News/Frontpage/091405/ss7.html. [Accessed 7 October 2005].

5.  Frequently Asked Questions (2006) [online]. Stem Cell Research Foundation. Available from: http://www.stemcellresearchfoundation.org/About/FAQ.htm. [Accessed 20 April 2006].