Rutgers New Jersey Medical School

GENERAL
What is a stem cell?	Back to Top
A stem cell is an uncommitted cell that has the potential to develop into cells of a specific tissue. As an example, the hematopoietic stem cells in the adult bone marrow can develop into all of the blood and immune cells. Stem cells are found in all organs of the fetus and adult.
What are Embryonic stem cells?	Back to Top
Embryonic stem cells are obtained from blastocysts that are donated from fertility clinics for the purpose of research. The clinics do not have the right to donate the embryonic stem cells. Only the couples who donated the egg and sperm can permit the use of the blastocyst. Donation of the blastocyst is accompanied with a signed permission referred to as a consent form. The embryonic stem cells can give rise to all cells of the body, including the adult stem cells.
What is a blastocyst?	Back to Top
Fertilization of an ovum and sperm develops into a zygote and then to a blastocyst. One blastocyst contained several embryonic stem cells (ESCs). A blastocyst has an outer layer referred as the trophoblast.
How are Embryonic Stem Cells generated?	Back to Top
This section describes two methods to generate ESCs from a blastocyst, which is derived from the in vitro fertilization clinics. First, the entire blastocyst is destroyed and the ESCs are expanded in the laboratory. Second, one or more ESCs can be taken from the blastocysts in a manner that save the blastocyst. This method is similarly use for preimplantation genetic testing while maintaining the viability of the blastocyst for implantation. It should be cautioned that preimplanting testing could inadvertently destroy the blastocyst.
What is preimplantation genetic testing?	Back to Top
In some cases parents have genetic mutations and the children who inherited the mutations from both parents have serious genetic abnormalities. Statistically, some of the offspring can be healthy. Rather than waiting until after birth to determine if the baby is healthy, the parent(s) opted for preimplantation genetic testing. This means that they will test the blastocytes from in vitro fertilization by selecting few embryonic stem cells and then select the blastocyst with the normal genes.
What is an Embryonic Stem Cell (ESC) Line?	Back to Top
An ESC line is expanded in the laboratory from only one blastocyst and not from mixtures of different blastocysts. The ESCs are passed in cultures for weeks to months to years.
Who provides funding for stem cell research?	Back to Top
In the USA, research with any type stem cells is supported by federal and private funds. Research with embryonic stem cells can be funded by federal funds if the cells were derived from blastocysts that were donated from a fertility clinic by the mom and dad. There should be documentation known as informed consent that the blastocyts were donated. A few states have passed legislative bills to fund embryonic stem cells as well as other cells. The states also support research with other types of stem cells. In New Jersey, there is currently no mechanism for state support of stem cell research. However, stem cell research is active at all if not most of the academic institutions. These include, but are not limited to research for tissue repair such as cardiac damage and, resetting of the immune system. The funding sources for research in New Jersey are from federal and private sources.
Do other stem cells exist in the fetus and how do they differ from their adult counterpart?	Back to Top
Stem cells can be found in the fetus. These stem cells were developed from the embryonic stem cells in order to generate specific organs such as the heart. It is difficult to assess if a stem cell from a fetal organ is functionally similar to the corresponding organ in the adult. It is presumed that the fetal stem cells would be functionally more primitive as compared to the adult stem cells. For example, hematopoietic stem cells in the fetal liver are more potent for transplant than those in the adult bone marrow. Examples of fetal stem cells are those found in fetal liver, bone marrow and yolk sac.
What are embryonic germ cells?	Back to Top
The embryonic germ cells are not generally discussed. These are stem cells that will eventually develop into oocytes (eggs) or sperm. Stem cells for oocytes (thecal stem cells) and sperms (spermatagonial stem cells) have been identified. Therefore, by extrapolation, perhaps the embryonic germ cells develop in thecal and spermatogonial stem cells. It is believed that the embryonic germ cells could behave similar to embryonic stem cells. However, in human these cells are not easy to obtain unless a pregnancy is aborted. There are also other scientific concerns involving the imprinting genes.
What are imprinting genes?	Back to Top
A person inherits two copies of every gene, one from the mother and one from the dad. When these genes are inherited they are functional except for a few that are called the imprinting genes. One copy of the imprinting genes is silenced in the original egg or the sperm. In this case, the gene is expressed only if it was not silenced in the mom or dad. The imprinted genes can be expressed differently in tissues and during development. Many of the imprinting genes have been linked to diseases, such as psychiatric disorders. It is unclear how imprinting occurs. What is known is the silencing is erased at some time during the development of germ cells towards the creation of the sperm and oocytes. The imprinting is then reset in the oocytes and sperm. It is this erasing and re-creation of the imprinting that might be a problem to use embryonic germ cells for tissue regeneration. Specifically, it is unclear which genes are erased when the stem cells are obtained. Tissues developed from the embryonic germ cells might have cells in which the imprinting is erased. Can the issue on erasing of the imprinting genes be overcome? The imprinting information is different among species. This can be studied in pregnant mice but the data cannot be extrapolated to human. Similar studies in human would be unethical.
What is umbilical cord blood?	Back to Top
Umbilical cord blood is taken from the cord, which is attached to the placenta. Since the blood belong to the baby, there are ethical concerns regard the time to clamp the cord. Umbilical cord blood is a major source of hematopoietic stem cells and other stem cells. The hematopoietic stem cells in cord blood are important for replacement of the immune system in adults. Despite the relatively low numbers, the hematopoietic stem cells in cord blood are relatively primitive as compared to those in adult bone marrow. The hematopoietic stem cells are functionally similar to those in the fetal liver. Due to this similarity, when a scientist needs to study human fetal liver hematopoietic stem cells, he or she can use umbilical cord blood cells.
What stem cells are in the yolk sac?	Back to Top
Among the role of the yolk sac, is the role to ensure that the embryo has adequate blood supply. The most studied stem cells in the yolk sac are those that develop into the hematopoietic system, which generates blood and immune cells. First the yolk sac generates hemangioblasts and this divides in parallel to hematopoietic stem cells and endothelial progenitors. The endothelial progenitors generate the blood vessels to accommodate the cells coming from the hematopoietic stem cells, such as macrophages and red blood cells. Eventually, the hematopoietic stem cells within the yolk sac migrate to the fetal liver and then to the bone marrow.
How are the hematopoietic stem cells developed in the embryo?	Back to Top
The hematopoietic stem cells are first detected in the yolk sac and the embryo. The hematopoietic stem cells are developed from another earlier stem cell, referred to as the hemangioblast. However, the early blood system formed from the hemangioblasts requires vessels. Therefore it is important that the hemangioblasts also form these vessels to accommodate the hematopoietic stem cells and the blood cells needed to sustain the embryo. Therefore, in parallel to the formation of hematopoietic stem cells, the hemangioblasts form angioblast, which develop into endothelial cells to form blood vessels.
Are hemangioblasts found in adults?	Back to Top
The experimental evidence indicates that hemangioblasts remain in the body after birth at very low frequency. Scientists are beginning to find markers to identify these cells. There is also evidence that in adults, the hematopoietic cell stem cells can show a reverse maturation to form hemangioblasts. This process is referred to as dedifferentiation. This method is controversial, but so far, no one has proved otherwise.
What are angioblasts?	Back to Top
The angioblasts are the endothelial progenitor cells. Although these cells were originally reported in the embryo as one of the two cells generated from the hemangioblast, more recent findings have found angioblasts in adults. The endothelial progenitor cells are capable of forming new blood vessels, as seen in the fetus. This process, in adults, is referred as post-natal vasculogenesis or neoangiogenesis. This is different from angiogenesis, which is the development of new blood vessels from preexisting vessels.
What is meant when one says that cord blood has primitive stem cells?	Back to Top
This point needs clarification because all stem cells are immature or primitive. In general, because the cord blood is taken from the new born, it is expected that all stem cells will be the most immature. However, this information is extrapolated from decades of studies in which the hematopoietic stem cells from cord blood were compared with those in the bone marrow. Scientists compared the differences in the two sources of stem cells to reconstitute the bone marrow, also referred as `bone marrow transplantation’. This is also referred to as the replacement of the hematolymphoid system, which is the method by which the hematopoietic stem cells generate immune and blood cells. The differences in reconstitution of the hematopoietic system define the cells’ relative level of maturity. The reconstitution of the hematopoietic system is insufficient to state that the cord blood cells are the most primitive. The relative primitiveness for hematopoietic stem cells is also based on the differences in serial transplants. Specifically, hematopoietic stem cells are transplanted into an animal that is cleared of its own stem cells. This could be achieved by several methods. Experimentally, it is done by lethal radiation. The animal is monitored for immune/blood reconstitution. The hematopoietic stem cells from the transplanted animal are collected and the process is repeated. Primitiveness is determined by the total number of times that this can be achieved, referred as the number of serial transplants.
What are induced pluripotent stem cells (iPS)?	Back to Top
iPS cells are reprogrammed adult cells into pluripotent stem cells. This can be achieved through the forced expression of ~four genes. The original derivation of iPS was done by Dr. Shinya Yamanaka and his colleagues at Kyoto University, Japan, 2006. The first report transfected the following genes, inserted in retrovirus, in fibroblasts: Oct 3/4, SOX2, c-Myc and Klf4. Subsequently, other non-viral methods and reduced number of genes have been applied.
What is the difference between embryonic stem cells (ESCs) and induced pluripotent stem cells (iPS)?	Back to Top
iPS, like ESCs can form cells of different tissues and can form teratomas. The teratomas are tumors with cells of the three germ layers (mesoderm, endoderm, ectoderm). However, the reports on genetic similarities indicate that these cells might be distinct. There are however similarities in gene expression. These similarities are not unique because ESCs also show overlapping gene with other stem cells.
Are there differences between embryonic and other stem cells?	Back to Top
Embryonic stem cells are required to make cells of all tissues of the body. Adult stem cells might be more specialized to generate cells of the organs where they are located. Note that the word `might’ is used because there are differences in opinion, based on the research literature. Regardless, adult stem cells show evidence of multipotency as well as pluripotency (Refer to definition section). As an example, stem cells in the bone marrow (hematopoietic stem cell) generate cells of the immune/blood system. Similarly, stem cells in the fetus, although in the early stages of maturation have been committed to cells of one organ. All stem cells are termed pluripotent, meaning one stem cell could form multiples types of cells. The difference between embryonic stem cells and other types of stem cells are the former can take the cells they produce to form whole body organs while the other stem cells form replacement cells within an organ.
Do adult and embryonic stem cells generate different types of cells?	Back to Top
Adult stem cells, which are found throughout the body, can be considered as a set of young cells or most primitive cell types. These cells can self-renew indicating that their numbers are maintained throughout life. The day-to-day function of an adult stem cell is to maintain, replenish and repair many tissues of the body. Embryonic stem cells, on the other hand, function to produce all the tissues of the body during development.
What is a cell lineage?	Back to Top
A cell lineage is the maturational pathway followed by a stem cell. The following diagram uses the hematopoietic stem cells as an example to explain lineage. Shown is a stem cell maturing to specialized blood cells. The path beginning at the level of the stem cell to the blood cells is a lineage.
What are the differences among pluripotent, multipotent and monopotent?	Back to Top
Lineage 1 Lineage 2 Lineage 3 Lineage 4 One should be careful how he or she designates cells as pluripotent or mulitpotent. These two words are defined differently depending on the writer. Therefore, whenever one reads an article, one should be careful how the word is defined. Pluripotency is defined as the most immature stage of a cell; hence the designation of stem cells as pluripotent. Multipotent cells should not be considered as stem cells. These cells can nonetheless form multiple cell lineages. A monopotent cell is still immature, but can differentiate alone one lineage.
Why is the designate `multipotency’ for a stem cell source contradict the function?	Back to Top
Mesenchymal stem cells (MSCs) are generally referred as multipotent cells. However, in many cases the MSCs have been shown to generate cells of multiple lineages. It is possible that MSCs are referred to as multipotent cells due to the need to be on the side of caution.
Are stem cells found in adults? If so, where are they located?	Back to Top
Stem cells are present in most if not all organs of the adult body and are called ‘adult stem cells’. The most studied adult stem cell is the hematopoietic stem cell, which is found in the healthy bone marrow.
What are the functions of adult stem cells?	Back to Top
First, we will discuss the most studied hematopoietic stem cells that can form all of the blood and immune cells. Similar to other stem cells, the formation of blood and immune cells occurs within a microenvironment that comprises cells, soluble factors and extracellular matrices. The microenvironment is referred as the supporting niche for the stem cells. In the case of hematopoietic stem cells in bone marrow, the main function for these stem cells is to be available to replenish blood and immune cells. Similar to other stem cells, the hematopoietic stem cells maintain homeostasis by replacing cells on a day-to-day basis. In the case of insults such as an accident when there is rapid blood loss, the hematopoietic stem cells are under stress and enhance the activity for rapid replacement of blood cells. The identification of stem cells in different organs, such as heart, brain, gut, skin etc indicate that these stem cells are also involved in day-to-day maintenance of the tissue. The property and differentiation ability of these stem cells are active subjects of research. A summary of each stem cell can be found in this site “Stem Cell Summaries”.
Can Stem cells from one organ form cells of another organ?	Back to Top
The experimental evidence indicates that it is relatively simple to generate specialized cells from stem cells of a different organ. These findings are currently tested in animal models. Although there is evidence to show that stem cells can cause tissue repair, it is unclear if the benefits are caused by new tissue formation. In this regard, the findings in the laboratory dishes might not be replicated in an animal. Despite the uncertainty in the mechanism by which stem cell showed improvement, the findings have led to several clinical trials. These trials are registered in clinicaltrial.gov. The most controversial in the field of stem cells forming cells of another organ is the ability of hematopoietic stem cells to form cells other than blood and immune cells. While some scientists have reported evidence that hematopoietic stem cells can repair tissues of other organs, such as cardiac tissue, others have proven otherwise. Cells from the bone marrow have been shown to contain cells that repair the liver. Later studies showed that the bone marrow cells did not form liver cells, but rather fused with the resident liver cells. Despite these negative results, interesting new information has been gained. For example, in the case of studies with liver repair, scientists have learned that there are genes that could be activated in response to injury that might provide answers in stem cell-mediate tissue repair.
Is it possible that additional stem cells exist in the adult and/or fetal organs?	Back to Top
Although scientists have identified many stem cells within the same organ, it is possible that there are additional stem cells to be identified. In adults, stem cells have been reported in many organs such as brain, termed neural stem cells, gut, gum, skin, heart, kidney, teeth etc. The complexity to find many types of stem cells in a particular organ is compounded by one set of stem cells showing heterogeneity (mixed). Ongoing research studies, in combination with new reagents will be able to identify each stem cell.
Can two different stem cells co-exist in the same organ?	Back to Top
The bone marrow is an example of an organ within the body where, at least two types of stem cells co-exist: Hematopoietic stem cells that form blood and immune cells, and mesenchymal stem cells that form osteoblasts, stroma, bone, cartilage etc. Functionally, these two stem cells might be linked. Specifically, the osteoblasts and stroma that are generated from the mesenchymal stem cells form part of the supporting niche to regulate the functions of hematopoietic stem cells. Investigations are uncovering additional stem cells in bone marrow. These studies are premature and require further investigations to identify the other stem cells and also to determine why multiple types of stem cells might be found in a single organ.
What is Mobilized Peripheral Blood (MPB)?	Back to Top
Mobilized Peripheral Blood is obtained from subjects who are infused with an agent (for example, granulocyte colony stimulating factor (G-CSF)) to get attract the bone marrow stem cells into the blood circulation. The stem cells that enter the blood are similar to those taken from bone marrow. Mobilized Peripheral Blood cells are obtained by methods similar to blood donation. This method replaces the old method of harvesting bone marrow cells directly from human iliac crest known as bone marrow aspiration. The mobilized stem cells are mixed, but contain hematopoietic stem cells. The mobilized hematopoietic stem cells can be transfused into subjects by the process known as `bone marrow stem cell transplantation'.
Can stem cells expand to generate large numbers?	Back to Top
The answer to this question depends on whether you would like to know if a stem cell can be expanded in vitro (in the laboratory) or in vivo (in the body) and also, the type of stem cell. While stem cells can replicate (termed expansion) without changing into a specialized cell type, there has to be a balance. Rapid expansion could predispose the cells to genetic changes. This will make the stem cells abnormal and could lead to tumor formation. The hematopoietic stem cells have been studied for decades and continue to be a subject of intense research. If these cells can be expanded in the laboratory, this will have an impact on bone marrow transplantation since a donor will provide a small amount of bone marrow aspiration for the expansion of hematopoietic stem cells. However, to date, the hematopoietic stem cells cannot be expanded in the laboratory. Hematopoietic cells can however be expanded in vivo for harvesting through blood collection. This can be achieved by mobilization from the bone marrow with G-CSF to the periphery for harvesting. However, once the hematopoietic stem cells taken out of the body, they cannot be expanded. Scientists have been able to expand other stem cells such as mesenchymal stem cells and placenta stem cells. However, it is possible that the expanded stem cells could have many subtle changes. An example of such change is modifications on molecules around the genes of the cell, termed epigenetic modification.
How does the niche influence the `behavior’ of stem cells?	Back to Top
The niche, also referred to as the microenvironment where stem cells reside could induce genetic changes in the stem cells. These can be normal to allow the stem cells to mature along a lineage for terminal differentiation. That means that the stem cells have formed specialized cells and are no longer stem cells. If stem cells are required for treatment and/or research, the the genetic changes, which induce differentiation, would be inappropriate and would lead to misleading results. The genetic changes can inadvertently occur in the laboratory dish when the stem cells are grown. These are issues that research has to confront as stem cells progress to patients. For these reasons, research studies are aimed at understanding how ‘stemness’ is maintained. If scientists fully understand the method to maintain cells as stem cells, it would be possible to expand stem cells outside of the body.

PHYSIOLOGY

Why do we need stem cells?

Stem cells function to replenish dead or lost cells in areas of the body, as needed. This could occur in the organ where the stem cell resides or in other organs. For example, bone marrow stem cells (also referred to as hematopoietic stem cells) would be able to replenish lost blood and provide new immune cells during infection. At the same time, these stem cells might have the capacity to detect damaged organs and migrate to repair the injured tissues. Another example is neural stem cells (brain). The exact role of these stem cells is not known. It is suspected that they may play a role in brain repair following injury and also in the replacement of dying neurons (brain cells). These subjects are the focus of active research in labs around the world.

In some cases, the function of a stem cell is linked to the organ where it resides. For example, a cardiac stem cell is considered to be a stem cell that repairs and/or replaces only cells of the heart. Other organs are irrelevant to the cardiac stem cell.

(Rosenthal N, N Engl J Med 2003;349:267; Nat Med 2002;8:647; Stewart et al, Blood 2001;98:1246; Burt et al, Blood 2002;99:768; Myers LA et al., Blood 2002;99:872)

CLONING

What is cloning?

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.

What is therapeutic cloning?

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.

Why is cloning associated with stem cell research? What is the difference?

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)

TISSUE REPAIR

What do we know about the ability of adult stem cells to repair tissues?

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.

(Morigi M et al, Blood 2001;98:1828; Ruggeri ZM, Blood 98:1644; Brummendorf TH et al, Exp Hematol 2003;31:475; Abedi M et al, Exp Hematol 2004;32:426; Simard AR & Rivest S, FASEB J 2004;18:998; Sigurjonsson OE et al, PNAS 2005;102:5227)

EMBRYONIC STEM CELLS

What is the relationship between the embryo and 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 the placenta.

(Gilbert DM, Med Sci Monit 2004;10:RA99; Rossant J, Stem Cells 2001;19:477; Nature 2001;414:122-8; Yamazaki Y et al., PNAS 2003;100:12207)

What is an “embryonic stem cell-line”? How does this differ from a primary embryonic stem cell?

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.

Why is the use of stem cells a political issue?

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)

Is embryonic stem cell research going on now?

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.

Why not use adult stem cells for research and stay away from the whole embryonic stem cell issue?

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

How could stem cells be used to treat spinal cord injury or Parkinson's 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.

What about cancer? Can stem cells be used to combat cancer?

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)

Can scientists use animal stem cells in humans and vice versa?

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)

Are there side effects following treatment with stem cells?

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)

Could stem cells implanted in the brain improve learning and/or memory?

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)

To date are there any successful treatments of patients using stem cells?

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)

If I do not have neurological damage or some other stem cell therapy-associated disease, why should I care about stem cells?

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

Is there a relationship between stem cells and cancer?

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 )

What is the difference between cancer stem cells and normal stem cells?

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)

Why are cancer stem cells a major health problem?

Scientists are working diligently all over the world to find the signature of the cancer stem cells. The question is: Do we have to find the signature of stem cells in different cancers or is there a common signature? Another possibility is that cancer stem cells and healthy stem cells share common signatures. These questions can be explained by the infamous vend diagram illustrated here.

Signature— Could be described as an ID-tag. The tag could be on the surface or inside the cells.

(Zhou S et al, Nat Med 2001;1028; Schwarzenberger P et al, Can Inves 2002;20:124; Yin AH et al, Blood 1997;90:5002; Murray LJ et al, Exp Hematol 1999;27:1282; Al-Hajj M et al, Curr Opinion Gen Develop 2004;14:43)

Are cancer stem cells normally present in the body?

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 cells.

(Reya T et al. Nature 2001;414: 105-111)

Can research on cancer stem cells help other health problems?

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

What are the current medical uses of 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)

Why do parents save their children's umbilical cord blood?

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

I have heard about stem cell transplants as a standard treatment for decades. What is this?

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)

What does a donor ‘match’ mean?

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.

Can stem cells from one person be given to another person?

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)