Department Of Medicine
EMBRYONIC STEM CELLS
USE OF STEM CELLS TO TREAT DISEASE
CANCER AND CANCER STEM CELLS
UMBILICAL CORD BLOOD
STEM CELL TRANSPLANTATION
Cloning is a procedure where the genetic material (DNA) of an individual is taken from an adult cell (for example, a skin cell) and then transferred into an oocyte (an egg). Before the adult cell DNA is placed into the egg, the scientist removes the egg's existing DNA. Thus, after the adult DNA is transferred into the egg, the new egg has the DNA of the skin cell. To put what would occur in perspective, if the skin cell is from Mr. Jones and the egg is from Ms. Smith, the egg is now converted into the DNA blueprint of Mr. Jones. The eggs are then treated chemically in the dish to develop into clones (exact replicas) of embryonic stem cells.
Therapeutic cloning is the same as cloning, except that it is designed only for the purpose of clinical treatment. For example, if a patient has liver damage, it is theoretically possible to manipulate the environment in which a cloned cell is growing so that it becomes a liver cell. If the cells are allowed to replicate, they can then regenerate the liver.
At times it is assumed that stem cell research is exclusively cloning. This is a misconception since stem cell research covers a wide range of topics – partly described in this FAQ section. At times it is difficult to separate stem cell research from cloning, since the latter might generate embryonic stem cells. To reiterate, the majority of stem cell research is exclusive of cloning. In general, most of the research studies aim to find cures for diseases with existing embryonic stem cells and also adult stem cells. In cases of therapeutic cloning and embryonic stem cell research, ethical considerations and current legal restrictions are always primary concerns of the investigator.
(Gurdon JB et al, PNAS 2003;100:11819; Mombaerts P, PNAS 2003;100:11924)
Some research studies show rare events by some adult stem cells to repair
tissue. Tissue repair by hematopoietic stem cells is controversial, due to
questions of cell fusion. However, hematopoietic stem cells have been
successfully used in bone marrow transplants to repopulate the immune and blood
systems. Research is ongoing to determine if adult stem cells can help repair
the damaged heart and brain, among other tissues.
EMBRYONIC STEM CELLS
The embryo is formed in early stages of fetal development and contains the
embryonic stem cell. During development, the embryonic stem cells begin the
process of forming tissues that will eventually compose the organs of the fetus.
Embryonic stem cells give rise to all of the tissues of the embryo, excluding
Under experimental conditions, a stem cell line is created when a single stem cell is allowed to divide (expand). These dividing cells, if maintained properly, will maintain their stem cell properties for a long period of time. Primary embryonic stem cells are those cells that have been directly obtained from the donor embryo. The expansion of primary embryonic stem cells is not generated from a single cell, but from all that were initially obtained from the embryo.
The use of embryonic stem cells in research is controversial because some individuals consider a stem cell as the earliest form of human life, and they believe they should not be tampered with. The use of adult stem cells, which are derived at birth, is not ethically controversial.
(Vogel G, Science 2003;302:1875)
With respect to federal funding for research, only the embryonic stem cell lines approved for research by President Bush in 2001 may be used. Detailed information on these cells can be found at: http://escr.nih.gov. Several laboratories around the country also conduct embryonic stem cell research using private funding. This research is monitored by an Institutional Review Board (IRB) within a privately funded institution.
Although there are many ethical and scientific issues with embryonic stem cells, these cells have the greatest capacity to make new tissues. To date, adult stem cells have not been shown to give rise to the variety of tissues that embryonic stem cells potentially can. Additionally, under certain conditions, embryonic stem cells can form cancerous cells. For this reason, embryonic stem cells have the potential to be studied as a model of cancer development.
USE OF STEM CELLS TO TREAT DISEASE
In spinal cord injury and Parkinson’s disease, the body is unable to naturally heal the damaged axons and dopamine-producing neurons of the spinal cord and brain, respectively. In spinal cord injury, loss of muscle and sensory function is seen below the site of the injury. In Parkinson’s disease, involuntary movements and tremors result from the damaged neurons in the brain. Current research is examining how stem cells can be used to make specific types of nerve cells to help promote repair and regenerate new neurons within these diseases.
Using stem cells to combat cancer is an interesting prospect. Research into this area is very new and novel. One research group found that they could use mesenchymal stem cells to deliver a cancer-toxic protein to developing tumors. Studies like this combine stem cells and gene therapy. In this study, the scientists engineered the mesenchymal stem cells to produce a specific protein (gene therapy), and made use of the migrating properties of the stem cell to deliver the “knock-out” blow.
(Nakamura K et al, Gene Ther 2004;11:1155)
We are unaware of experiments that place animal stem cells into humans. Research studies are ongoing where human stem cells are placed into animals. However, the studies are only experimental and they are performed under strict regulation by the participating institution. The facts gained from these experiments will provide valuable information for future therapies using stems cells. Hopefully, these experiments will pave the way for getting stem cells to the bedside of patients. It should be noted that animals undergoing these types of studies are not allowed to survive, but are euthanized using humane methods.
(Inzunza J et al, Stem Cells 2005;23:544)
There are issues that have to be considered as a person undergoes stem cell therapy. An obvious concern is the development of unwanted tissue types in the region undergoing treatment. For example, we would not want bone to be formed in the liver if the goal was to regenerate the liver. Rejection is another concern, even though current clinical practice ensures a match between donor and host. Some adult stem cells appear to be resistant to rejection. These adult stem cells are seriously considered for treatment. The formation of cancer cells (teratomas) from embryonic stem cells is another major potential side effect of any embryonic stem cell-based therapy.
(Kuramotot K et al, Blood 2004;103:4070; Kirk AD et al., Nat Med 2002;8:553; Farag SS et al, Blood 2002;100:1935; Reviewed Exp Hematol 2000;28:479; Takahashi K et al, Nature 2003;423:541)
While there is some evidence in animal studies that learning correlates with the birth of new stem cells, the use of stem cells in humans to improve memory is not supported by any current research. However, it is true that if neural stem cell therapy can be used to prevent the death of neurons in Alzheimer's disease, then the decline in mental ability in those patients could be slowed or prevented.
(Schaffer DV and Gage FH, Neuromolecular Med 2004;5:1)
Yes. Bone marrow stem cell transplantation has been a standard form of care for immune cell replacement since the late 1960s/early 1970s. Historically speaking, the first transplant occurred in 1958 to care for a radiation accident. To date, children with leukemia have been known to survive following stem cell transplant. One research study showed that children with leukemia receiving bone marrow stem cell transplantation had a 63% survival rate at 5 years following the transplant.
(Farag SS et al, Blood 2002;100:1935; Baker D et al, J Pediatr Hematol Oncol 2004;26:200; Perry AR and Linch DC, Blood Rev 1996;10:215)
On the surface, stem cells might seem irrelevant to you because you lack any of the disorders mentioned on TV, such as: spinal cord injury, diabetes etc. However, stem cells could be important to any disease due to their unique property of being forever ‘young’ and being responsive to change. An understanding of these properties would lead to insights into the biology of other diseases. For example, an individual might have a condition that could eventually lead to a stem cell disorder such as leukemia. By understanding the biology of stem cells, drugs could be developed to prevent the dysfunction of stem cells.
CANCER AND CANCER STEM CELLS
Some researchers believe that cancer is maintained by a few cancer stem cells, while others believe that it could be a normal stem cell “gone wrong”. Research on any type of stem cells is likely to lead to a better understanding of cancer stem cells. Once this information is fully understood, drugs can be developed to kill the cancer stem cells and thereby improve cancer treatment.
(Pardal R et al. Nature Reviews 2003;3: 895-902; Reya T et al. Nature 2001;414: 105-111; Al-Hajj, M & Clarke MF. Oncogene 2004, 23: 7274-7282 )
Cancer stem cells share many characteristics with normal stem cells. For example, a normal stem cell can self-renew, which means the daughter cells retain their numbers and properties/functions as the mother cells. Cancer stem cells also maintain the ability to self-renew. A few cancer stem cells could evade treatment and later give rise to a tumor, referred to as cancer relapse. The tumors formed are really the progenies of the cancer stem cells. Like all progenies of stem cells, they multiply rapidly. However, the progenies of cancer stem cells are not like normal progenies, whose growth are tightly controlled so that there is never too many or too few. The cancer stem cell could be considered as a normal stem cell “gone wrong”. A major difference between the progenies of a normal stem cell and those from a cancer stem cell is that progenies of normal stem cells eventually form mature cells, whereas progenies of cancer stem cells form rapidly dividing progenitor cells which do not fully mature.
(Reya T et al. Nature, 2001;414: 105-111; Pardal R et al. Nature Reviews 2003;3:895-902; Reya T et al. Nature 2001;414:105-111)
At this time no one knows the answer to this question. There may be a few
cancer stem cells that are part of our normal tissues that are not detected by
current clinical methods. If the cells never develop into tumors or spread to
other tissues, then this may be normal for the body. If these cells do lead to
cancer, then they become a medical problem. For this reason, it is necessary to
understand all aspects of stem cell biology. Research into the basic biology and
chemistry of cancer stem cells will allow drug companies to develop the
appropriate medication to rid the body of these few cancer stem
The origin of cancer stem cells is still unclear. An appropriate analogy to this dilemma would be: Which came first, the chicken or the egg? Just as we do not know which came first, researchers still are unsure whether cancer stem cells come from a normal stem cell gone wrong or the progeny of a stem cell taking on the property of the mother stem cells.
(Reya T et al, Nature 2001;414:105; Pardal R et al, Nature Review 2003;3:895; Al-Hajj & Clarke MF, Oncogene 2004;23:7274; Al-Hajj et al, Curr Opinion Gen Develop 2004;14:43)
For additional information regaring cancer and stem cell research, please visit the New Jersey Medical School/University Hospital - Cancer Center.
UMBILICAL CORD BLOOD
Umbilical cord blood stem cells are mostly used in stem cell transplantation to replace bone marrow cells. For reasons yet unknown, these cells pose less of a risk for rejection when compared to bone marrow stem cells. Due to the limited amount of cord blood, there is generally an insufficient number of cells for adult transplants.
(Ballen KK, Blood 2005;105:3786; Chen BJ et al., Blood 2001;99:364)
Umbilical cord blood is stored because it has a higher number of hematopoietic stem cells than bone marrow. Mothers generally save their babies' umbilical cord blood in case something is wrong, such as the baby needing a stem cell transplant while he or she is still a child. If, for example, the baby develops leukemia, he or she could be infused with his or her own umbilical cord blood. Another point to keep in mind is that the use of umbilical cord blood does not have the controversy associated with it that embryonic stem cells does.
(Ballen KK, Blood 2005;105:3786)
STEM CELL TRANSPLANTATION
Bone marrow stem cell transplants have been commonplace since the late 1960s/early 1970s. The therapy was developed as a method to replace new stem cells in the bone marrow and has been successfully used in patients with cancer. Scientists are able to withdraw the patient’s own bone marrow stem cells, treat the patient for the cancer and then re-infuse the bone marrow stem cells. In other cases, patients receive bone marrow from a matched donor.
(Parkan P & McQueen KL, Nature Rev Immunol 2003;117:108; Suzuki Y et al, Stem Cells 2005;23:365; Askenasy N et al., Stem Cells 2003;21:200; Rondelli D et al, Blood 2005;105:4115 ; Drouet et al, Stem Cells 19:436, 2001; Glimm H et al, Blood 2003;99:3454; Perry AR and Linch DC, Blood Rev 1996;10:215)
A donor ‘match’ means that the host will not reject the donor's stem cells. This could only occur if the stem cells from the donor and host have similar genetic blueprints, as seen in family members or in twins.
Yes, if the two people are matched. That is, cells of the host (the person getting the cells) and donor (the person donating the cells) do not reject each other. This type of sharing is successful in bone marrow transplantation in cancer patients.
(Spyridonidis A et al, Blood 2005;105:4147; Parkan P & McQueen KL, Nature Rev Immunol 2003;117:108; Korblin M & Anderlinin P, Blood 2001;98:2900)