Stem Cells and Cord Blood

Cells that have the ability to self-replicate and give rise to specialized cells. Stem cells can be found at different stages of fetal development and are present in a wide range of adult tissues. Many of the terms used to distinguish stem cells are based on their origins and the cell types of their progeny.

There are three basic types of stem cells. Totipotent stem cells, meaning their potential is total, have the capacity to give rise to every cell type of the body and to form an entire organism. Pluripotent stem cells, such as embryonic stem cells, are capable of generating virtually all cell types of the body but are unable to form a functioning organism. Multipotent stem cells can give rise only to a limited number of cell types. For example, adult stem cells, also called organ- or tissue-specific stem cells, are multipotent stem cells found in specialized organs and tissues after birth. Their primary function is to replenish cells lost from normal turnover or disease in the specific organs and tissues in which they are found.

Totipotent stem cells occur at the earliest stage of embryonic development. The union of sperm and egg creates a single totipotent cell. This cell divides into identical cells in the first hours after fertilization. All these cells have the potential to develop into a fetus when they are placed into the uterus. The first differentiation of totipotent cells forms a hollow sphere of cells called the blastocyst, which has an outer layer of cells and an inner cell mass inside the sphere. The outer layer of cells will form the placenta and other supporting tissues during fetal development, whereas cells of the inner cell mass go on to form all three primary germ layers: ectoderm, mesoderm, and endoderm. The three germ layers are the embryonic source of all types of cells and tissues of the body. Embryonic stem cells are derived from the inner cell mass of the blastocyst. They retain the capacity to give rise to cells of all three germ layers. However, embryonic stem cells cannot form a complete organism because they are unable to generate the entire spectrum of cells and structures required for fetal development. Thus, embryonic stem cells are pluripotent, not totipotent, stem cells.

Embryonic germ (EG) cells differ from embryonic stem cells in the tissue sources from which they are derived, but appear to be similar to embryonic stem cells in their pluripotency. Human embryonic germ cell lines are established from the cultures of the primordial germ cells obtained from the gonadal ridge of late-stage embryos, a specific part that normally develops into the testes or the ovaries. Embryonic germ cells in culture, like cultured embryonic stem cells, form embryoid bodies, which are dense, multilayered cell aggregates consisting of partially differentiated cells. The embryoid body-derived cells have high growth potential. The cell lines generated from cultures of the embryoid body cells can give rise to cells of all three embryonic germ layers, indicating that embryonic germ cells may represent another source of pluripotent stem cells.

Much of the knowledge about embryonic development and stem cells has been accumulated from basic research on mouse embryonic stem cells. Since 1998, however, research teams have succeeded in growing human embryonic stem cells in culture. Human embryonic stem cell lines have been established from the inner cell mass of human blastocysts that were produced through in vitro fertilization procedures. The techniques for growing human embryonic stem cells are similar to those used for growth of mouse embryonic stem cells. However, human embryonic stem cells must be grown on a mouse embryonic fibroblast feeder layer or in media conditioned by mouse embryonic fibroblasts. Human embryonic stem cell lines can be maintained in culture to generate indefinite numbers of identical stem cells for research. As with mouse embryonic stem cells, culture conditions have been designed to direct differentiation into specific cell types (for example, neural and hematopoietic cells).

Adult stem cells occur in mature tissues. Like all stem cells, adult stem cells can self-replicate. Their ability to self-renew can last throughout the lifetime of individual organisms. But unlike embryonic stem cells, it is usually difficult to expand adult stem cells in culture. Adult stem cells reside in specific organs and tissues, but account for a very small number of the cells in tissues. They are responsible for maintaining a stable state of the specialized tissues. To replace lost cells, stem cells typically generate intermediate cells called precursor or progenitor cells, which are no longer capable of self-renewal. However, they continue undergoing cell divisions, coupled with maturation, to yield fully specialized cells. Such stem cells have been identified in many types of adult tissues, including bone marrow, blood, skin, gastrointestinal tract, dental pulp, retina of the eye, skeletal muscle, liver, pancreas, and brain. Adult stem cells are usually designated according to their source and their potential. Adult stem cells are multipotent because their potential is normally limited according to their source and their potential. Adult stem cells are multipotent because their potential is normally limited to one or more lineages of specialized cells. However, a special multipotent stem cell that can be found in bone marrow, called the mesenchymal stem cell, can produce all cell types of bone, cartilage, fat, blood, and connective tissues.

Blood stem cells, or hematopoietic stem cells, are the most studied type of adult stem cells. The concept of hematopoietic stem cells is not new, since it has been long realized that mature blood cells are constantly lost and destroyed. Billions of new blood cells are produced each day to make up the loss. This process of blood cell generation called hematopoiesis, occurs largely in the bone marrow. Another emerging source of blood stem cells is human umbilical cord blood. Similar to bone marrow, umbilical cord blood can be used as a source material of stem cells for transplant therapy. However, because of the limited number of stem cells in umbilical cord blood, most of the procedures are performed for young children of relatively low body weight.

Neural stem cells, the multipotent stem cells that generate nerve cells, are a new focus in stem cell research. Active cellular turnover does not occur in the adult nervous system as it does in renewing tissues such as blood or skin. Because of this observation, it had been a dogma that the adult brain and spinal cord were unable to regenerate new nerve cells. However, since the early 1990s, neural stem cells have been isolated from the adult brain as well as fetal brain tissues. Stem cells in the adult brain are found in the areas called the subventricular zone and the ventricle zone. Another location of brain stem cells occurs in the hippocampus, a special structure of the cerebral cortex related to memory function. Stem cells isolated from these areas are able to divide and to give rise to nerve cells (neurons) and neuron-supporting cell types in culture.

Stem cell plasticity refers to the phenomenon of adult stem cells from one tissue generating the specialized cells of another tissue. The long-standing concept of adult organ-specific stem cells is that they are restricted to producing the cell types of their specific tissues. However, a series of studies have challenged the concept of tissue restriction of adult stem cells. Although the stem cells appear able to cross their tissue-specific boundaries, crossing occurs generally at a low frequency and mostly only under conditions of host organ damage. The finding of stem cell plasticity carries significant implications for potential cell therapy. For example, if differentiation can be redirected, stem cells of abundant source and easy access, such as blood stem cells in bone marrow or umbilical cord blood, could be used to substitute stem cells in tissues that are difficult to isolate, such as heart and nervous system tissue.

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Umbilical Cord Blood

Following the birth of a baby, the umbilical cord usually is discarded along with the placenta. However, it is now known that blood retrieved from the umbilical cord is a rich source of stem cells. Stem cells are unspecialized blood cells that produce all other blood cells, including blood-clotting platelets and red and white blood cells. Like donated bone marrow, umbilical cord blood can be used to treat various genetic disorders that affect the blood and immune system, leukemia and certain cancers, and some inherited disorders of body chemistry. To date, more than 45 disorders can be treated with stem cells from umbilical cord blood.

Currently, commercial companies provide services to parents to store their newborn baby’s cord blood. Prospective parents who are considering this option should have as much information as possible to make an informed decision.

What are stem cells and why are they valuable?

Blood stem cells, most often found deep in bone marrow, are the factory of the blood system. They continually make new copies of themselves and produce cells that make every other type of blood cell. Stem cells are the key to successful bone marrow transplantations (BMTs) because they continue to manufacture blood cells indefinitely.

Bone marrow transplants can be lifesaving for people with leukemia (cancer of the white blood cells) and other cancers, or for those with serious blood disorders, such as aplastic anemia, in which the body does not produce enough blood cells. Stem cells can help enhance a person’s blood producing capability and immune system that are impaired through an inherited (genetic) defect or that have been severely damaged or deliberately destroyed by cancer treatments. At present, donated bone marrow is the most common source of stem cells.

What are the advantages of stem cells from cord blood?

Studies suggest that stem cells from cord blood offer some important advantages over those retrieved from bone marrow. For one thing, stem cells from cord blood are much easier to get because they are readily obtained from the placenta at the time of delivery. Harvesting stem cells from bone marrow requires a surgical procedure, usually under general anesthesia, that can cause post-operative pain and poses a small risk to the donor.

A broader range of recipients may benefit from cord blood stem cells. These can be stored and transplanted back into the donor, to a family member or to an unrelated recipient. For a bone marrow transplant to succeed, there must be a nearly perfect match of certain tissue proteins between the donor and the recipient. When stem cells from cord blood are used, the donor cells appear more likely to “take” or engraft, even when there are partial tissue mismatches.

A potentially fatal complication called graft versus host disease (GVHD), in which donor cells can attack the recipient’s tissues, appears to occur less frequently with cord blood than with bone marrow. This may be because cord blood has a muted immune system and certain cells, usually active in an immune reaction, are not yet educated to attack the recipient. A 2000 study found that children who received a cord blood transplant from a closely matched sibling were 59 percent less likely to develop GVHD than children who received a bone marrow transplant from a closely matched sibling.

The use of cord blood may make blood stem cell transplants available more quickly for people who need them. About 30,000 individuals each year are diagnosed with conditions that could be treated with a bone marrow transplant. Approximately 25 percent of these individuals have a relative who is an appropriate tissue match. While suitable donors can be located for many through national bone marrow registries, the process can take months. Donors can be located within 4 months for about 50 percent of patients. It often is more difficult to find a bone marrow match for members of non-white ethnic and racial groups; transplants from cord blood may make timely treatment available for more of these individuals. Banked stem cells from cord blood can be more readily available, and this can be especially crucial for patients with severe cases of leukemia, anemia or immune deficiency who would, otherwise, die before a match can be found.

Cord blood also is less likely to contain certain infectious agents, like some viruses, that can pose a risk to transplant recipients.

In addition, some studies suggest that cord blood may have a greater ability to generate new blood cells than bone marrow. Ounce for ounce, there are nearly 10 times as many blood-producing cells in cord blood. This fact suggests that a smaller number of cord blood cells are needed for a successful transplantation.

In addition, cord blood stem cells offer some exciting possibilities for gene therapy for certain genetic diseases, especially those involving the immune system. Donald Kohn, MD, and colleagues at the Children’s Hospital of the University of Southern California in Los Angeles and the University of California in San Francisco, made the first attempt at gene therapy with cord blood in 1993 in three children suffering from adenosine deaminase (ADA) deficiency, a potentially fatal defect that cripples the immune system. The children, who also receive additional drug treatment, appear healthy to date, even though their blood now carries only a small amount of the gene introduced into their stem cells.

Source: http://www.marchofdimes.com/professionals/681_1160.asp

Cord Blood, storage and costs

Umbilical cord blood is human blood from the placenta and umbilical cord that is rich in hematopoietic stem cells. Cord blood is collected after the umbilical cord has been detached from the newborn, and utilized as a source of stem cells for transplantation. Cord blood is stored by both public and private cord blood banks. Public cord blood banks store cord blood for the benefit of the general public, and most U.S. banks coordinate matching cord blood to patients through the National Marrow Donor Program (NMDP). Private cord blood banks are for-profit organizations that store cord blood for the exclusive use of the donor or donor's relatives.

Public cord blood banking is strongly supported by the medical community. However, private cord blood banking is generally not recommended unless there is a family history of specific genetic diseases. Private banking is unlawful in France and Italy, and opposed by the European Group on Ethics in Science and New Technologies. See cord blood bank.

Properties
Cord blood stem cells are more proliferative and have a higher chance of matching family members than stem cells from bone marrow. Fathers have a 25% chance of matching their child's cord blood stem cells. Siblings have a 25% chance of being a perfect cord blood match.

Collection, storage and costs

There are 2 main methods in cord blood collection from the umbilical vein; before the placenta is delivered (in utero) or after (ex utero.)

With ex utero collection method, the cord blood is collected after the placenta is delivered and the umbilical cord is clamped off from the newborn. The placenta is placed in a sterile supporting structure with the umbilical cord hanging through the support. The cord blood is collected by gravity drainage yielding between 40-150 mL.

A similar collection method is done for in utero except that the cord blood is collected after the baby has been delivered but before the delivery of the placenta.

After collection the cord blood units must be immediately shipped to a cord blood bank facility. At public cord blood banks, this blood is then analyzed for infectious agents and the tissue-type is determined. Cord blood is processed and depleted of red blood cells before being stored in liquid nitrogen for later use.

New parents have the option of storing their newborn's cord blood at a private cord blood bank or donating it to a public cord blood bank. The cost of private cord blood banking is approximately $2000 for collection and approximately $125 per year for storage as of 2006. The donation of cord blood may not be available in all areas, however the opportunity to donate is becoming more available. Several local cord blood banks across the United States are now accepting donations from within their own states. The cord blood bank will not charge the donor for the donation, but the OB/GYN may still charge a collection fee of $100-$250, which is usually not covered by insurance. However, many OB/GYNs choose to donate their time.

"According to research in the Journal of Pediatric Hematology/Oncology (1997, 19:3, 183-187), the odds that a child will need to use his or her own stem cells by age twenty-one for current treatments are about 1:2,700, and the odds that a family member would need to use those cells are about 1:1,400."

In 2005, University of Toronto researcher Peter Zandstra developed a method to increase the yield of cord blood stem cells to enable their use in treating adults as well as children.

Source: http://www.answers.com/topic/cord-blood

What are the facilities used for the collection and storage of cord blood?

Both commercial and non-profit facilities (cord blood banks) collect and store cord blood. Cord blood banks that operate for the general public collect and store cord blood that is donated for use by anyone who might need it in the future (unrelated allogeneic use). Some commercial facilities charge fees to collect and store cord blood for a family's own private use, in the event it is needed by the donor infant (autologous use) or an HLA-matched family member (related allogeneic use) at a later time.

Storage for private use is controversial when it is purely "speculative" and no specific family member has been identified as needing a transplant. The American Academy of Pediatrics does not recommend private storage for purely speculative purposes. Cord blood cannot be used autologously, for example, for children with genetic diseases because the same disease would be returned with the transplant. Moreover, most transplant physicians do not recommend autologous cord blood transplants for children with leukemia. Most will have cells with the leukemic mutations in their blood at birth. Moreover, a child who develops leukemia has evidence that his or her own immune system already failed to prevent the leukemia. Thus, physicians fear that an autologous cord blood transplant would have little if any graft versus leukemia effect. It also should be noted that only 25% of any two siblings are fully-matched for their HLA tissue type.

A family's choosing to store their baby's cord blood for their own private use must make arrangements in advance with a storage company. Usually the family will sign a contract with the company, pay an initial fee, obtain the company's special cord blood collection kit and get their obstetrician's agreement to do the collection. Initial and annual storage fees vary and may be covered by health insurance.

Non-profit cord blood banks do not charge for collecting and storing donated cord blood. They do require the mother to complete a thorough health history and to be tested for viruses such as hepatitis and HIV (also free of charge). The process may be initiated during pregnancy or before or immediately after the delivery, but is completed in the hospital.

Source: http://l3.leukemia-lymphoma.org/all_mat_toc.adp?item_id=9622

Cord Blood yields 'ethical' embryonic Stem Cells

Hopes for treating disease with stem cells from umbilical cord blood has received a major boost, following the discovery of primitive cells with clinical potential matching that of the far more controversial embryonic stem cells (ESCs). The latter are originally derived from human fetuses, which are then destroyed, and have become a major ethical issue, especially in the US.

Furthermore, the same team is applying new microgravity technology - originally developed by NASA for the International Space Station - to make large enough quantities of the stem cells to repair tissue damage in patients.

The newly discovered human cells, named “cord-blood-derived embryonic-like stem cells” or CBEs, are not quite as primitive as embryonic stem cells, which can give rise to any tissue type of the body. But they appear to be much more versatile than “adult stem cells” such as those found in bone marrow which repair damaged tissue during life.

“We have found a unique group of cells that bring together the essential qualities of both types of stem cells for the first time,” says Colin McGuckin of Kingston University in Surrey, UK, who co-led the team with colleague Nico Forraz.

In laboratory experiments, the team successfully coaxed CBEs into becoming liver cells. They also showed that the cells have most of the surface “markers” considered as identifiers of embryonic stem cells and form “embryoid bodies” – characteristic clumps of cells formed by ESCs.

Ethically acceptable

But the factor that may make the discovery very significant is that umbilical cord blood can be saved, stored and multiplied without any of the ethical dilemmas facing embryonic stem cell use, which are derived from human fetuses.

And with more and more “banks” around the world for saving cord blood, the potential for finding tissue matches for every patient becomes more and more realistic. “There are now eight banks in the UK alone,” says McGuckin.

Stephen Minger, director of the Stem Cell Biology Laboratory at King's College London, UK, says he is "intrigued" by the claims but would like to see more proof of the cells' embryonic character. Can they, for example, differentiate into the three fundamental cell types that go on to form all adult tissues, he asks. McGuckin says his team has already shown this, and that the work is awaiting publication.

Free-floating production

The technology used by the team to start multiplying the CBEs was originally developed for NASA by Synthecon Incorporated in Houston, Texas, US, for isolating proteins with clinical potential from cells grown aboard the International Space Station.

The spinning devices used essentially put "the cells in a constant state of freefall in a liquid", McGuckin explains. He says that in these free-floating “three-dimensional” conditions, the cells grow faster than if grown in “two dimensions” in a lab dish.

Nor do they need to be nourished from underneath by “feeder layers” of animal cells which have been shown to contaminate human cells grown, making them unsuitable for use in medical treatments.

“We’re now developing a new bioreactor to make considerably more, which means we can make thousands and thousands more stem cells than are available from embryonic sources,” says McGuckin.

Journal reference: Cell Proliferation (vol 38, p 245)

Source: http://www.newscientist.com/article.ns?id=dn7864

Stem Cells and Cord Blood... The future

What are the potential uses of human stem cells and the obstacles that must be overcome before these potential uses will be realized?

There are many ways in which human stem cells and cord blood can be used in basic research and in clinical research. However, there are many technical hurdles between the promise of stem cells and the realization of these uses, which will only be overcome by continued 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. Scientists know that turning genes on and off is central to this process. Some of the most serious medical conditions, such as cancer and birth defects, are due to abnormal cell division and differentiation. A better understanding of the genetic and molecular controls of these processes may yield information about how such diseases arise and suggest new strategies for therapy. A significant hurdle to this use and most 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 example, new medications could be tested for safety on differentiated cells generated from human pluripotent cell lines. Other kinds of cell lines are already used in this way. Cancer cell lines, for example, are used to screen potential anti-tumor 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 the specific cell type on which drugs will be tested. Current knowledge of the signals controlling differentiation fall well short of being able to mimic these conditions precisely to consistently have identical differentiated cells for each drug being tested.

Perhaps the most important potential application of human stem cells is the generation of cells and tissues that could be used for cell-based therapies. Today, 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. Stem cells, directed to differentiate into specific cell types, offer the possibility of a renewable source of replacement cells and tissues to treat diseases including Parkinson's and Alzheimer's diseases, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis.

For example, it may become possible to generate healthy heart muscle cells in the laboratory and then transplant those cells into patients with chronic heart disease. Preliminary research in mice and other animals indicates that bone marrow stem cells, transplanted into a damaged heart, can generate heart muscle cells and successfully repopulate the heart tissue. Other recent studies in cell culture systems indicate that it may be possible to direct the differentiation of embryonic stem cells or adult bone marrow cells into heart muscle cells (Figure 4).

In people who suffer from type I diabetes, the cells of the pancreas that normally produce insulin are destroyed by the patient's own immune system. New studies indicate that it may be possible to direct the differentiation of human embryonic stem cells in cell culture to form insulin-producing cells that eventually could be used in transplantation therapy for diabetics.

To realize the promise of novel cell-based therapies for such pervasive and debilitating diseases, scientists must be able to easily and reproducibly manipulate stem cells so that they possess the necessary characteristics for successful differentiation, transplantation and engraftment. The following is a list of steps in successful cell-based treatments that scientists will have to learn to precisely control to bring such treatments to the clinic. To be useful for transplant purposes, stem cells must be reproducibly made to:

- Proliferate extensively and generate sufficient quantities of tissue.
- Differentiate into the desired cell type(s).
- Survive in the recipient after transplant.
- Integrate into the surrounding tissue after transplant.
- Function appropriately for the duration of the recipient's life.
- Avoid harming the recipient in any way.
- Also, to avoid the problem of immune rejection, scientists are experimenting with different research strategies to generate tissues that will not be rejected.

To summarize, the promise of stem cell therapies is an exciting one, but significant technical hurdles remain that will only be overcome through years of intensive research.

The NIH has a wide array of new scientific programs designed to support research that uses embryonic stem cell lines.

Source: http://stemcells.nih.gov/info/basics/basics6.asp

Cord blood usage in infant medicine

Cord blood is the name given to the human blood of the placenta, together with the umbilical cord, which is resulted after giving birth to a child. The recent medical innovations and discoveries include saving and using this cord blood for potential further medical operations, as its stern cells are of high importance and appropriation in various medical cases.

After collecting the cord blood in maximum 15 minutes after the baby is born, processing it is the following faze in order to be viable for further medical operations. The processing of cord blood includes specific steps, such as RBC depletion, shipping and the actual freezing. The freezing or, scientifically said, the cryopreservation is applied within 1 day after the actual collection and can be successfully preserved for indefinite years.

There are various pediatric solutions that include using the cord blood. The most major ones are the children cancers and blood diseases, including infant leukemia (juvenile chronic myelogenous leukemia and juvenile myelomonocytic leukemia) or immune system disorders. All these are usually treated with chemotherapy, which, besides its benefic effects, also negatively affects some good cells. A significant cord blood usage in infant medicine is the marrow transplant. This procedure has the result of providing new and healthy blood cells, which leads to a safer immune system of the child. Besides these, there are some rare genetic diseases that require cord blood stem cells. Among these rare disorders, there is the fatal Krabbe Disease, which is characterized by causing severe degeneration of mental and motor skills of the child.

If receiving the stem cells from the umbilical cord before the actual manifestation of the symptoms, the brain development can be successfully preserved. Hurler Syndrome, Adrenoleukodystrophy, Metachromatic Leukodystrophy, Tay-Sachs disease, Sandhoff disease are also other rare and severe conditions that affect the infants and can be successfully treated if using the cord blood stems. Hurler’s Syndrome is a genetic and progressive disorder that results from the body’s incapacity to make a significant enzyme. The disease damages many organs and most importantly, it affects the heart and causes death in the early teens. The Sandoff disorder has a result the progressive deterioration of the central nervous system and, like the Krabble disease, it is fatal before the age of 3.

Cord blood is not used as a temporary solution in serious medical cases of infants. Cord blood actually provides a new and healthy blood structure that increases the safety of the immune system and prevents further imbalances.

Author: Michael Rad