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Stem Cell Science
Most of the stem cells in cord blood are blood-forming stem cells, also known as “hematopoietic” stem cells or HSC. The presence of HSC is what enables cord blood transplants to be used as a substitute for bone marrow transplants.
However cord blood transplants have advantages and disadvantages compared to stem cell transplants from adult donors. The main advantage of cord blood is that it does not have to be exactly matched to the patient like transplants from an adult donor. The main disadvantages are that it is hard to collect enough cord blood to transplant an adult, and cord blood stem cells are slow to engraft.
Cord blood also has applications in regenerative medicine. This is due to a combination of additional types of stem cells in cord blood, plus the fact that the cells in cord blood release chemicals that signal the body to heal itself. These chemicals are called cytokines and the cell-to-cell signalling is called the paracrine effect.
Over the past decade infusions of cord blood stem cells have been used around the world as therapy for infants with cerebral palsy and other brain injuries. Published studies have shown that cord blood stem cells benefit young children with neurologic injury, even though the mechanism of action is not yet fully understood. More studies against control groups are in progress.
In the United States, cord blood stem cells have been used in a clinical trial for adults with stroke, and more trials are planned for demyelinating diseases like multiple sclerosis. In China, cord blood stem cells are in a trial for spinal cord injury.
Min K et al. Stem Cells 2013; 31(3):581-591 doi: 10.1002/stem.1304
Cotten M. et al. 2013; Pediatrics 164(5):973–979 doi:10.1016/j.jpeds.2013.11.036
Liao Y et al. 2013; Bone Marrow Transplantation 48:890-900 doi:10.1038/bmt.2012.169
Sun JM et al. 2015; Pediatric Research 2015; 78:712–716 doi:10.1038/pr.2015.161
Kurtzberg J. 2014; presentation at ISCT meeting
Umbilical cord tissue and the tissue of the placenta are rich sources of mesenchymal stem cells (MSC). Currently MSC are the most popular form of stem cells that are being used in clinical trials and are appearing in academic publications. MSC show great promise for treating a wide variety of auto-immune disorders and treating injuries to muscle or bone (sports injuries, heart disease). The MSC from birth sources, such as cord tissue and the placenta, grow faster than MSC from adult donors and have never been exposed to disease.
Perinatal Stem Cells 2nd edition 2013; book published by Wiley
Collecting Cord Blood
It literally only takes minutes to save the stem cells in cord blood. Once the umbilical cord is clamped, it is wiped with antiseptic and a needle is inserted into one of the veins in the umbilical cord to withdraw a few ounces of blood.
There are three methods of collection in common use. One is to hang a blood bag lower than the mother and let gravity draw blood down the tube into the bag. This method is used in most countries of the world, because it has the fewest steps, and therefore the fewest opportunities for mistakes or contamination.
The second method is to actively draw the blood out, just like when a person has a blood draw for a medical test. The draw can be done with a standard syringe or with a bulb in the tubing of the blood bag that creates suction. Studies have shown that actively drawing the blood will collect a larger volume faster.
Third, some banks collect cord blood "ex utero" which means "outside the uterus". They wait until the placenta is delivered, and then a trained technician takes it into another room and puts it on a high shelf so that all of the blood in the umbilical cord and some from the placenta can be drained.
2. Sterilize before every needle stick. When in doubt, sterilize again!
3. Volume, volume, volume. You want to "milk the cord" for as much blood as possible. If the blood vessel you are using stops working, try another or move upstream, but sterilize first.
The median size of cord blood collections in family banks is 60mL or 2 ounces. That small volume of blood corresponds to 470 million Total Nucleated Cells (TNC) or 1.8 million cells that test positive for the stem cell marker CD34. Thus, most healthy full-term babies have over a million blood-forming stem cells in their umbilical cord blood. By comparison, most public cord blood banks will only keep collections that are much bigger than average, and throw out the donations that are below a threshold of a billion TNC, corresponding to a blood volume of about 100 mL or 3 ounces.
Sun, JJ et al., Transfusion Sept. 2010; 50(9):1980-1987 doi:10.1111/j.1537-2995.2010.02720.x
When a baby is delivered by an obstetrician, the umbilical cord may be clamped and cut within seconds of birth. The phrase "delayed cord clamping" is defined as a 30-60 second wait before clamping the umbilical cord. If the umbilical cord is still pulsating, and the baby is positioned so that blood can flow through the cord, then delayed clamping will allow the newborn to receive some of the stem cell rich blood in the umbilical cord.
Studies have shown that, in parts of the world with poor nutrition or poor infant health care, delayed cord clamping can help protect the baby from anemia (low blood counts) for up to 6 months after birth. Medical studies have shown that delayed clamping is very valuable to protect premature babies from bleeding in the brain, but the value of delayed cord clamping for full-term babies in developed nations is only marginal, despite numerous studies. One study of full-term babies born in Sweden found that the group with delayed cord clamping had slightly higher social skills at age 4 years old, but that study has not been confirmed by other groups so far.
The World Health Organization (WHO) has issued an international guideline to delay cord clamping by one minute. In the United States, the American College of Obstetricians and Gynecologists (ACOG) has issued an opinion stating that clamping should be delayed 30-60 seconds.
van Rheenen, P et al., Tropical Med. and Internal Health 2007; 12(5):603-616 doi:10.1111/j.1365-3156.2007.01835.x
Andersson, O. et al. JAMA Pediatrics 2015; 169(7):631-638 doi:10.1001/jamapediatrics.2015.0358
When to clamp the umbilical cord for full term babies? Dr. Elisabeth Semple Dec. 2016 Parent's Guide to Cord Blood newsletter
WHO Guideline: Delayed umbilical cord clamping for improved maternal and infant health and nutrition outcomes. Geneva: World Health Organization; 2014.
ACOG Committee Opinion. Timing of Umbilical Cord Clamping After Birth. Number 543, December 2012. Reaffirmed 2014.
ACOG Committee Opinion. Delayed Umbilical Cord Clamping After Birth. Number 684, January 2017.
You can delay cord clamping if you are storing cord blood privately for your family, but if you plan to donate cord blood then it is not advisable to delay cord clamping.
The goal of delayed cord clamping is to allow some of the blood in the umbilical cord to flow into the newborn. This is most likely to happen in the first 30-60 seconds after birth. Waiting beyond that point will not add significantly to the blood volume that the newborn receives, but will significantly decrease your ability to get a cord blood collection. As the blood flow in the umbilical cord slows down the blood starts to clot, making it difficult to collect the cord blood.
It is a fact of nature that delayed cord clamping results in smaller cord blood collections. That is OK in a family banking setting, where the bank is not imposing a strict volume limit to store the collection. It is also OK for therapies that do not require high stem cell counts. For example, delayed clamping would be fine if you are concerned about saving stem cells to protect your newborn against cerebral palsy or autism, but delayed cord clamping could be a problem if you are trying to get enough stem cells for a transplant of an older sibling.
Public cord blood banks have a minimum size requirement for storage of cord blood donations. When cord clamping is delayed beyond 60 seconds the volume of cord blood collected drops seven fold and only a few percent of cord blood collections qualify for donation to a public bank.
Delayed clamping of the umbilical cord after delivery and implications for public cord blood banking. Allan DS et al. Transfusion. Mar 2016; 56(3):662-5. doi: 10.1111/trf.13424
Timing of Umbilical Cord Clamping and Impact on Cord Blood Volume Collected for Banking. Rodica Ciubotariu, MD PhD, Dec. 2016 Parent's Guide to Cord Blood newsletter
Donate Cord Blood
Health requirement: The donor registry Be The Match has a short pre-screening questionnaire where you can learn if you can donate cord blood. Before the actual donation, the mother would have to undergo a more detailed maternal health screening. Here is another article about the health requirements from our Foundation's newsletter.
Location requirement: Less than 200 hospitals in the United Sates have programs to accept cord blood donatins, and they are all large birthing centers located in communities with racially diverse populations. Those parents who are not delivering at a hospital that accepts donations can try to register for a mail-in donation.
Timing requirement: Most donation programs require the mother to register in advance, typically by week 34 of the pregnancy (the due date is at 40 weeks). A few donation programs will sign up mothers during labor for permission to collect the cord blood, then if the collection qualifies for public banking they will go back to the mother before she leaves the hospital to get a full informed consent.
Although a few such cases have actually happened, it is very very unlikely to get your cord blood back once it is donated. Donating cord blood is not a way of banking for your family for free.
When a mother signs the Informed Consent form to donate cord blood, she gives up any guaranteed access to that blood. First of all, the public bank may throw the blood out simply because it does not meet their size threshold, or simply because the paperwork is not complete. Secondly, even if the blood does make it into public storage, it may be released to some one else.
Unlike organ donors, cord blood donors do not receive any priority treatment or waived fees if your child later needs a donor. The reward for donating cord blood is the possibility that your baby may Be The Match that saves a life.
In the United States, about 80% of cord blood donations are discarded. The primary reason is that the collection volume is too small. Public banks exist to provide transplants for patients throughout the world, and hence they only store cord blood donations that are big enough to transplant a large child or small adult. On top of that medical requirement to only accept the bigger collections, in recent years public banks have raised their storage thresholds in response to economic pressures.
Magalon et al. 2015 Banking or Bankrupting: Strategies for Sustaining the Economic Future of Public Cord Blood Banks PLOS ONE doi:10.1371/journal.pone.0143440
If you live in the United States, we have a searchable map of all hospitals that accept cord blood donations. We are the only website that has a complete map and we work in partnership with the national donor registry Be The Match to update it quarterly.
In other countries we do not have this level of detailed information. Your best option is to look up the list of public banks in your country and contact them to find out where they accept donations.
Within the United States, there are a few programs that provide parents with a collection kit that they can take to the hospital and then send a mail-in donation to a public cord blood bank or a research laboratory. These programs are not financially efficient, and therefore are very limited. As of 2010 there used to four public banks that accepted mail-in donations for the national transplant registry, but as of 2016 the only one still providing this service is the Cord for Life program at Lifeforce Cryobanks in Florida. Another option is the mail-in donation program at Sanercon CCEL, where cord blood is used for research to develop cures for neurodegenerative diseases like Alzheimer's. The Saneron program also has the convenience that the medical history is less strict and the deadline to register is more flexible.
There is no medical reason why parents should have to register for cord blood donation weeks in advance. Given adequate staffing and efficient management, a public cord blood bank could check the mother's health history and offer the family Informed Consent when they arrive at the hospital to give birth. Examples of public cord blood banks in the Untied States that accept walk-in donations are the NY Blood Center and the Cleveland Cord Blood Center.
However, most public cord blood banks in the United States do not have enough dedicated staff to handle donation requests, so in order to process them they require that mothers register weeks ahead of their due date. About five years ago the registration deadline was at 36 weeks, but as of 2016 the deadline is 34 weeks gestation.
No - cord blood that has already been stored in a family bank cannot be transfered to a public bank. When a public bank collects cord blood donations that will potentially be released to strangers, they are required to perform a very detailed family health history and collect a sample of the mother's blood. This screening must be performed at the time of donation and it cannot be retroactively performed for cord blood in a family bank.
Find a Family Bank
Usually the answer is yes. However... some hospitals have signed exclusive contracts requiring their patients to use certain family cord blood banks, so it is best to check in advance.
Those hospitals that have exclusive partnerships with certain family cord blood banks will argue that it improves their level of care, because their staff train with and stock the collection kits for the banks they have approved. The hospital probably has a financial incentive too. However, for parents it means a lack of consumer choice.
The Parent's Guide to Cord Blood Foundation recommends that parents select a Family Bank whose laboratory has been inspected by an accreditation agency specific to cord blood banking: AABB or FACT. This provides a degree of quality assurance.
In some countries, national regulations hold Family Banks to the same standards as Public Banks, so an independent accreditation is not necessary. But in most countries the federal requirements for Family Banks are not as strict as Public Banks, and then a voluntary accreditation is desirable. For example, in the United States the FDA registers and inspects Family banks, but does not require them to have a Biologics License (BLA) like Public Banks.
Caveat: The process of registering with an accreditation agency and getting inspected can take a year, so it is understandable if a brand new lab does not have an accreditation yet.
It is best to store cord blood in the country where the baby is born, provided a quality bank is available. If you currently live in one country and plan to store cord blood in your home country, make sure that your family bank has a shipping container that is well insulated and carries a temperature logger.
The important thing to know is that fresh cord blood that is traveling into the bank has a shelf life, whereas when the bank sends out cryogenically frozen cord blood to a clinic it does not expire.
After birth, the cord blood is shipped to the laboratory at room temperature. Every hour that it spends in transit, stem cells are gradually dying. Ideally the cord blood should arrive at the laboratory and be processed within 48 hours of birth. Sending the cord blood on a long airplane flight or a series of connecting flights is an additional risk for cell loss, unless the blood travels in the passenger compartment and is protected by a well-insulated shipping container.
By comparison, if a day should come where you need to use the cryopreserved stem cells, they will be shipped to the treatment center frozen and only thawed upon arrival. So on the release side of banking, cord blood stem cells can travel anywhere n the world with no loss of viability because they travel frozen.
You can preserve cord blood from twins in a family bank, but not in a public bank.
Public banks have a policy against accepting cord blood donations from twin births. One argument often heard is that the bank is afraid that the babies might be confused at birth. However obstetricians are trained to keep track of which baby is which in a multiple birth. The primary reason that public cord blood banks do not accept twin donations is that twins tend to be smaller than singletons, thus they have less cord blood in the umbilical cord and the placenta, and in public banking it is crucial to get large donations. The chances are so low that both twins have enough cord blood to be over the storage threshold for transplants, that public banks just do not accept registrations from moms who are pregnant with twins.
Family banks have no problem accepting cord blood from twin births. Parents might have a problem paying for double cord blood banking, but almost every family cord blood bank offers special discounts for twin births.
Some parents ask if they should save the cord blood for both twins or only one? It is better biological insurance to save newborn stem cells from both twins. In the case of fraternal twins, the babies are distinct individuals with different DNA. In the case of identical twins, the babies have identical DNA. However, one identical twin may develop a genetic mutation later in life that causes a disease while the other does not. If that happens, then the healthy twin is the perfect matching stem cell donor, and there have been transplants where one identical twin donated cord blood to another.
Cord blood donation is free to the family, but public banks only operate donation programs at large birthing hospitals located in ethnically diverse communities. Also the mother has to register by the 34th week of gestation and pass a health screening.
For those families who want to preerve newborn stem cells privately, our website provides a list of family cord blood bank prices in each country.
Parents often complain that cord blood banking cost is expensive. This is not an industry where costs can be cut by running a turn-key operation. Each cord blood unit must be individually tested and processed by trained technicians working in a medical labortory.
To explain costs in the United States, we have an article from Dr. Dennis Todd, CEO of a public cord blood bank, that breaks down the steps in the laboratory process and itemizes the cost of each one. Even before the cord blood arrives at the laboratory, it should be shipped in a container that is thermally insulated to maintain constant temperature. Very often the less expensive family cord blood banks are cutting corners on the temperature stability of their collection kit.
Shipping Cord Blood and Cord Tissue to the Bank
In order to protect the internal kit temperature during cord blood shipments, Parent's Guide to Cord Blood Foundation recommends that parents select a family cord blood bank that has a well insulated transportation container, preferably with a temperature logger.
The standard protocol for transporting fresh cord blood is to keep it near room temperature within the range from 15 °C (59 °F) to 25 °C (77 °F). Priority shipping services may guarantee the arrival time, but they do not guarantee the temperature conditions during transit. Ambient temperature can get too hot or too cold while the package is sitting in the back of a truck, on a loading dock, or in the cargo hold of an airplane. This is why a well insulated container, preferably one that has been validated to IATA standards, is important.
In the United States, the post 9/11 security requirements of the Transportation Security Administration (TSA) require that specialty medical couriers can only offer cord blood shipping through cord blood banks that are registered with the TSA as a "Known Shipper". Before 9/11, specialty couriers could market their services directly to consumers, and in some countries this is still possible. Parents should check if their family bank offers specialty courier services before they sign a contract.
Public cord blood banks throughout the world have adopted a time window of 48 hours as the maximum delay from birth to the initiation of lab processing. It would be a "best practice" if family banks also followed the 48 hour window.
Some data points:
- FACT accreditation standards require the 48 hour window for public donations but allow 72 hours for family banks.
- AABB accreditation standards do not specify a time window.
- The US FDA recommends the 48 hour window.
- The US state of NY Dept. of Health requires a 48 hour window.
Laboratory Processing of Cord Blood
The earliest cord blood transplants were performed with whole cord blood. Thus, it is not absolutely necessary to process cord blood in order to save patient lives. There has never been a prospective randomized trial to compare transplant patient outcomes with cord blood that had been stored whole versus processed.
Today most cord blood banks, both public and private, process cord blood to remove both the plasma and the red cells, and cryo-preserve the remaining "buffy coat" that holds both white blood cels and stem cells.
Many doctors consider it important to remove red blood cells before preserving cord blood stem cells, and we have a fact sheet on red blood cell depletion. The reason to remove the red blood cells is because they tend to burst during freezing, which releases iron from hemoglobin that can be toxic. The alternate to removing the red cells before freezing is to wash any broken cells out of the cord blood unit upon thaw.
The three main components of cord blood, like any blood collection, can be separated by weight: the heaviest layer is the red blood cells (RBC), the lightest is the plasma (a clear white liquid), and in the middle is a pinkish layer called the "buffy coat" which contains the white blood cells (WBC), including stem cells. When banks process the cord blood, the final separated component that goes into storage is the buffy coat, even though only about 1% of the cells are actually stem cells. There is no procedure to separate out the stem cells alone.
The vast majority of blood processing methods rely on the different density of the three main blood components. They can be separated by sedimentation, or by centrifuge, or by a combination of the two techniques. The procedure can be performed manually by trained technicians or by automated machine.
Accreditations are quality standards. We describe each one on our Accreditation Standards page.
Cord blood laboratories that are located in certain countries are required by federal law to follow high standards: these include GMP in Germany, HTA in the UK, Swissmedic in Switzerland and TGA in Australia.
In the United States, public cord blood banks are required to get a Biologics License from the FDA, but family cord blood banks are only required to register with the FDA and undergo surprise inspections.
There are two voluntary accreditation systems that have been developed specifically for cord blood banking and are based on inspections of the laboratory procedures: AABB and FACT. By comparison, ISO accreditation is not specific to cord blood banking. Parent’s Guide to Cord Blood Foundation recommends that parents choose a family bank that has AABB or FACT accreditation, if one is available in your country. In our 2015 Cord Blood Industry Report, we found that accredited cord blood banks are NOT more expensive on average that banks with no accreditation.
These are all ways of counting cell types, and they tell you whether or not your cord blood collection has lots of stem cells and if they are healthy.
Stem cells happen to be Mono-Nuclear Cells or MNC: when you look at them under a microscope there is only one nucleus. Unfortunately, one of the most difficult aspects of stem cell biology is that you can't identify a stem cell just by looking at it. There are other types of blood cells which are also MNC, such as nucleated red blood cells. The only proof that a cell is a stem cell comes from how it behaves when it multiplies.
Scientists have worked for years to develop various chemical stains which have a high affinity for stem cells. The best known marker for blood-forming stem cells is that they test positive for CD34, a protein found on the surface of stem cells. But, CD34+ counts are not an accurate measure of stem cells: CD34+ results vary between labs, they can vary within a single lab, and only 1-2% of the MNC that have CD34+ are actually stem cells.
The Total Nucleated Cell count or TNC is the test most often reported as a measure of the cell count after cord blood processing. The main advantage of measuring TNC is that the count is highly reproducible within and among labs, so it can be used accurately throughout the blood banking community. Even better, the TNC count can be automated with the use of a device called a flow cytometer.
At present Colony Forming Units or CFU are considered to be the best measure of whether stem cells are "viable", or quite frankly alive. The TNC count includes both living and dead cells. In the CFU test a small portion is watched under controlled conditions to see if stem cells divide and form colonies. This used to be a subjective measure, but recently it has been standardized with technology to image the cells and count colonies in the image. The only remaining problem with the test is that it takes days for colonies to grow.
Manual processing is when cord blood is handled in the laboratory by trained technicians. These technicians should be wearing gowns and gloves and handling the cord blood inside a laminar flow cabinet. Automated processing is when the cord blood collection bag goes into a functionally closed device like the Sepax 2 made by Biosafe or the AXP made by Cesca Therapeutics. In automated processing the laboatory technicians do not handle the cord blood during processing. When processing is completed by either manual or automated methods, a technician will always manually transfers the final storage bag to a controlled rate freezer
Advantages and Disadvantages of Automated Processing:
- Advantage: There are less opportunities for technician errors or the introduction of contaminants during processing.
- Automated processing may be a better approach in countries where it is hard to train and retain experienced technicians.
- Disadvantage: Automated processing is much more expensive. First, the laboratory has to purchase two devices, in case one breaks. Second, the devices use disposable kits which add significantly to the operating expenses.
- Automated processing makes sense in busy laboratories that handle a higher volume of cord blood business.
Advantages and Disadvantages of Manual Processing:
- Advantage: Manual processing is much less expensive.
- Manual processing makes sense in countries where highly skilled labor is easily available and affordable.
- Advantage: Manual processing is better for processing the smallest family collections because the procedures can be customized as needed.
These rumors are totally false. In fact, our 2015 Cord Blood Industry Report found that the majority of family cord blood banks in the United States and Canada are processing cord blood manually with hespan. Hespan or HES is a brand name for the chemical hydroxyethyl starch. It is commonly used in most laboratories that handle blood.
The source of the rumors about hespan is the following: Up until recently, it was a standard procedure in emergency rooms to give a large infusion of hespan to patients who were going into shock from loss of blood pressure. The idea was to briefly replace their blood volume with hespan while the ER doctors were rushing to fix whatever problem had caused a rapid loss of blood pressure, and while waiting for a matching transfusion from the nearest blood bank. However, retrospective studies have recently found that patients who survived this experience were likely to develop kidney failure later. Hence, doctors now realize that infusing large volumes of hespan intravenously is not safe. However, the use of small volumes of hespan in cord blood processing is still perfectly safe.
Zarychanski R. et al. 2013; JAMA 309(7):678-88. doi:10.1001/jama.2013.430.
Questions Parents should ask a Family Bank
- What instructional tools are provided in the kit for the physician and delivery staff?
- Will the family banking provider actively contact the labor and delivery staff for you?
- Does the hospital have designated staff that are trained to collect cord blood?
- What collection method does the bank use: gravity drip or blood draw?
- Is the collection blood bag sterile, both inside and out, so that it can be used in the operating room for a C-section?
- Does the bank provide the option of collecting additional stem cells from the tissue of the umbilical cord or the placenta?
- Is the cost of shipping included in the contract?
- Does the shipping company offer bed-side pick-up?
- Has the shipping container been tested for temperature stability?
- Does the shipping container include a temperature logger?
- On weekends, are the laboratory staff in-house or on-call?
- Does the bank guarantee to get the blood to the laboratory and processed within a certain time window?
- If the bank uses a medical courier, does the courier have possession of the cord blood throughout transit? (Sometimes the courier sub-contracts to another shipping company that is not a medical courier)
- Is the cord blood laboratory accredited by an agency that has specific standards for cord blood banks and conducts inspections? (ex: AABB, FACT)
- If you live in one of the US states that license cord blood banks (CA, MD, NJ, NY) then you can only use a family bank that has your state license.
- Does the lab process cord blood around the clock, or only on selected shifts?
- What tests does the lab perform on maternal blood?
- What tests does the lab perform for infectious disease markers?
- What tests does the lab perform for contamination?
- Does the lab ever reject cord blood collections on the basis of the tests of maternal blood, infectious diseases, or contamination?
- Does the lab maintain a "quarantine tank" for the storage of blood while they are waiting for tests of infectious disease markers?
- What tests does the lab perform to measure the stem cell count of the processed cord blood and the stem cell viability?
- Does the bank inform parents, prior to storage, if the collection is too small for a transplant, and give them the option not to save it?
- Does the bank offer parents a refund if the cord blood collection has certain problems (contamination, low volume)? These refunds are typically only offered if the bank performed the collection as part of their service.
- What information will parents receive in the final report about their stored cord blood?
- What type of records do parents receive after storage?
- Does your contract state that the storage fee is fixed, or may it increase later?
- Does the bank reserve the right, in your contract, to change storage facilities?
- Does the bank operate their own storage facility, or is it provided by another laboratory?
- What type of accreditation does the storage facility carry? In most banks the cord blood is stored in the lab where it was processed, and the accreditation of the lab covers the storage conditions.
- What is the geographic location of the storage facility: Is it at risk for hurricanes, earthquakes, or other natural disasters?
- What type of back-up systems does the storage facility have in case of power failure?
- What type of security systems does the storage facility have?
- Does the bank collect the whole umbilical cord or only a segment?
- Does the bank freeze the umbilical cord intact or process it before storage?
- Does the bank store a tissue product (for example minced cord) or a cellular product (isolated cells from the tissue)?
- If the bank stores a tissue product, have they validated that upon thawing this tissue they can retrieve viable stem cells? This means not just testing for markers of stem cells but confirming there are cells that can grow in culture.
- If the bank stores isolated cells, what tests do they run to characterize the populaton of cells that go into storage?
- Does the bank culture the isolated cells to expand their numbers before storage?
- Does the bank offer any guarantees about the number of or quality of cord tissue stem cells that the bank will provide if the client requests them for therapy?
- Does the bank have AABB accreditation for tissue processing (a somatic cell activity)?
- Is the family cord blood bank a publicly-held or privately-held company?
- Is the company affiliated with a hospital or research institution?
- Is the company involved in bio-technology research and development?
- What other medical services does the company perform?
- How long has the company been banking cord blood?
- Who directs the day-to-day business of the company? Many cord blood banks have famous doctors on their Board of Directors; but they are not involved with the day-to-day operations.
- What is the lab inventory of cord blood collections, both public and private? This demonstrates their experience with storing cord blood.
- How many cord blood collections has the bank released from their own lab for therapy? This demonstrates their experience with releasing cord blood.
- Are there any coupons currently available? Most banks are constantly running a "special limited time offer".
- Is the enrollment fee charged once per family, or for each birth?
- Is the first year of storage included in the processing fee?
- If there is an annual storage fee, is it guaranteed not to increase?
- Are there any discount programs? Some banks offer discounts to medical professionals or military personnel.
- Do parents have the option of a partial or full refund if they decide not to store the cord blood for any reason? For example, if the lab tests show contamination and the cord blood should not be saved, what happens? Full refunds are typically only offered in situations where the bank provided staff to perform the collection service.
- Should the family ever need the cord blood, will the bank charge to release it or to ship it?
Stem Cell Transplants with Cord Blood
The crucial thing is not the volume of the cord blood collection, but the number of stem cells it contains. Transplant doctors develop recommendations based on the Total Nucleated Cell count, or TNC, because it is the easiest measure to reproduce between different labs.
When treating cancer, the transplant dose should be at least 25 million TNC per kilogram of patient body weight (1 kilogram equals 2.2 pounds). The average cord blood collection holds 8.6 million TNC per mL. Thus, the optimal transplant dose requires harvesting:
1.3 mL of cord blood for every pound of patient weight, -or-
2.9 mL of cord blood for every kg of patient weight
Reed, W et al., Blood 2003;101(1):351 doi:10.1182/blood-2002-02-0394
Barker, JN et al., Blood 2005;105:1343-1347 doi:10.1182/blood-2004-07-2717
Eapen, M et al. Lancet 2007;369:1947-54 doi:10.1016/S0140-6736(07)60915-5
Rocha & Gluckman Brit. J. Haematology 2009;147(2):262-274 doi:10.1111/j.1365-2141.2009.07883.x
The term "HLA" is short for Human Leukocyte Antigens, and these are proteins in the immune system that determine whether a patient will react against a donor transplant. A very good basic tutorial about HLA types is on the Stanford Website, and the donor registry Be The Match explains the role of HLA Typing and Matching in stem cell transplants on their clinical website.
Briefly, there are 6 HLA types that are important for stem cell transplants: in a bone marrow transplant the patient and donor must match at all 6 (100% match), whereas a cord blood transplant is just as effective at curing patients with only a 4 out of 6 match (67% match) between donor and patient. This is the reason that cord blood donations are so important to help patients who come from minority or mixed racial backgrounds.
The HLA type of cord blood is always measured by public banks, and then the type is listed on a registry that can be searched by patients seeking a transplant. Family banks typically do not measure the HLA type at the time of banking, because it is an expensive lab test and and can always be checked later from a testing segment of the stored cells.
In general sibling donors are better than unrelated donors for stem cell transplants. The exact comparison depends on the patient's diagnosis and the stage of disease.
The two important measures of patient outcome after a stem cell transplant are: long-term survival, and the amount of graft-versus-host disease (GvHD) that the patient suffers. Sibling donors trigger less GvHD, so that quality of life is better post-transplant. Also, sibling donors are available faster than searching for an unrelated donor, and patients have better survival when they go to transplant faster after diagnosis.
Some case by case studies: For many adult cancers the outcomes of transplants from siblings versus unrelated donors are comparable, although sibling donors have a slight edge. One large study was by Weisdorf et al. 2002, for over 2900 patients with CML leukemia. When correcting for all other factors, the survival with sibling donor vs unrelated donor was 68% vs. 61%. However, in pediatric transplants for hereditary disorders, sibling donors have a distinct advantage. The European Blood and Marrow Transplantation Group (EBMT) reported in 2011 that three year survival rates were 95% from a sibling donor vs. 61% from an unrelated donor.
The donor registry Be The Match has a section of their clinical website which reviews this topic here.
Weisdorf, D.J. et al. Blood 2002; 99:1971-1977. doi:10.1182/blood.V99.6.1971
Bizzetto, R. et al. (EBMT) Haematologica 2011; 96(01):134-141 doi:10.3324/haematol.2010.027839
Yes, stem cell transplants with cord blood have been used to cure both children and adults with leukemia since the early 1990's. To date, there have been over 35,000 cord blood transplants world-wde, and most of them were for leukemias and other blood disorders (Ballen Verter Kurtzberg 2015). A study published in the New England Journal of Medicine (NEJM) in Sept 2016 compared cord blood transplants versus bone marrow transplants for leukemia patients. The two groups had comparable survival post-transplant, but the cord blood patients tended to live longer and most importantly the cord blood patients were less likely to relapse.
The important caveat is that children with leukemia or another blood disorder must receive a cord blood transplant from a donor, NOT their own cord blood. It turns out that when children and even adolescents develop leukemia, they were born with the genetic defect that triggered the leukemia... hence it is not safe to give them a transplant with their own cord blood because it probably carries the mutation for leukemia.
Backtracking leukemia to birth: Gale KB et al. 1997; Proc Natl Acad Sci USA. 94(25):13950-4. PMID:9391133
Backtracking leukemia to birth: Janet D. Rowley 1998; Nature Medicine 4:150-1 PMID:9461182
Ballen KK, Verter F, Kurtzberg J 2015; Bone Marrow Transplantation 50(10):1271-8. doi:10.1038/bmt.2015.124
HealthDay article describing study in Sept 2016 NEJM: Cord Blood Transplants Show Promise in Leukemia Treatment
Filippo Milano, et al. 2016; NEJM 375:944-953. DOI:10.1056/NEJMoa1602074
A child with cancer can sometimes be treated with autolgogous (their own) cord blood, and there are a few dozen documented cases from family cord blood banks, but it is very rare. Childhood cancers make up less than 1% of all cancers diagnosed each year. The most common childhood cancer is leukemia, and we have another FAQ, "Can cord blood cure leukemia?", which explains that childen with leukemia and other blood diseases should receive cord blood transplants from a donor, not their own blood. However, children with cancerous solid tumors like neuroblastoma, medulloblastoma, and retinoblastoma can receive transplants of their own cord blood. The very first case in the world where a child was given a transplant of her own cord blood happened in 1998 for a girl in Brazil who had neuroblastoma.
Regenerative Medicine with Cord Blood
All the reasons that you banked for the first child are still valid for additional children.
1. If you want the baby to have the option of using his/her own cells, then you need to bank them.
2. If you are banking as a form of "biological insurance" for siblings, then the ability to use cord blood from one child for another depends on whether they have matching HLA type. Two full siblings have a 25% chance of being a perfect match, a 50% chance of being a half match, and a 25% chance of not matching at all. The more siblings with banked cord blood, the more chance that they cover each other for possible transplants or other therapies for which sibling stem cells are an option.
Odds of sibling match are based on haplotype inheritence: that the child will receive 3 HLA types as a group from each parent.
Indefinitely. From an economic perspective, it does not make sense to invest in the up-front processing fee and pay for years of annual storage, and then throw out the investment. That would be like buying life insurance and then cancelling it because you have not died yet. Especially given that the probability of some one in the immediate family needing a transplant increases with age. Even if the cord blood collection was small, and the child becomes too large to use it for a transplant, it could still be enough cells for a regenerative medicine therapy. Stem cells which have been cryogenically preserved remain viable for decades. It has been confirmed that cord blood stem cells were still viable after being frozen 23+ years.
Broxmeyer, H.E. Cell Stem Cell 2010; 6(1):21-24
Mazur, P. Science 1970; 168(3934):939-949
Nietfeld, J.J. et al. BBMT 2008; 14:316-322
Cryogenically frozen cord blood can be stored for decades and still be a viable source of stem cells for therapy. This conclusion is based on studies by Dr. Hal Broxmeyer, the man who invented cord blood storage in the 1980's. He contributed an article "How Long Can Cord Blood Be Stored?" for our newsletter of Sept. 2014.
The odds of using your baby's cord blood are the same as the probability that your baby or a close family member will have a disease that can be treated with cord blood.
Family cord blood banks are contantly telling parents that there are 80 diseases for which stem cell transplants are a standard treatment. That is a true statement, but it can be misleading. Most of those 80 diseases are rare among children. In the United States, the net probability that a child will need any type of stem cell transplant by age 20 is 3 in 5,000 or .06%. So the odds of use for transplant of a child are only 3 in 5000 for all of the 80 diseases combined!
When does cord blood stored in family banks have significant odds of use?
Family members: The graph on the left illustrates that, as people get older, rates of cancer increase, and the cumulative probability of having a stem cell transplant increases. In the United States, 1 in 217 people, or .46%, will have a stem cell transplant (not just need one, but have one) by age 70. Hence the cord blood that parents store from their baby might be of help to an immediate family member years from now. The cord blood is most likely to match first degree relatives: siblings and parents.
Inherited disorders: The odds of use quoted for the average person in the United States do not apply to some families and do not apply at all in other countries.
For example, some parents are very intersted in cord blood banking because they have many relatives with an auto-immune disorder like multiple sclerosis, and they know that stem cell transplants show promise for auto-immune diseases.
In Asian countries where the inheried blood disorder thalassemia is prevalent, family cord blood banks are filling a public health need. Families can bank cord blood from a healthy baby to provide a sibling cord blood transplant to an older child with thalassemia. In Thailand we profiled a fertility clinic that helps parents of a child with thalassemia to conveive a matched savior sibling.
Regenerative medicine: Parents in the United States are most likely to need their baby's cord blood to treat pediatric neurological disorders such as: hypoxic-ischemic encephalopathy (HIE), apraxia, ataxia, cerebral palsy, hydrocephalus, autism, in-utero stoke, traumatic bran injury, and similar conditions. No one wants to imagine that their child might be born with a brain injury, but the reality is that it happens in 2 of 1,000 full term births and among pre-term boths it is 10 times more common; 2 in 100 premies or 2% have cerebral palsy. Another relatively prevalent condition that may benefit from trials of cord blood therapy is autism spectrum disorders, which impact 1 in 68 US children.
Please see our page about cord blood Odds of Use.
Lifetime Probability of Stem Cell Transplant in USA: Nietfeld JJ, Pasquini MC, Logan, BR, Verter, F, Horowitz MM 2008; BBMT 14(3)316–322 doi:10.1016/j.bbmt.2007.12.49
Medical publications about cord blood therapy for pediatric neurologic disorders:
Cotten M. et al. 2013; Pediatrics 164(5):973–979 doi:10.1016/j.jpeds.2013.11.036
Liao, Y, Cotten, M, Tan, S, Kurtzberg, J & MS Cairo, MS 2013; Bone Marrow Transplantation 48:890-900 doi:10.1038/bmt.2012.169
Min et al. Stem Cells 2013; 31(3):581-591 doi: 10.1002/stem.1304
Sun, J et al. Transfusion Sept. 2010; 50(9):1980-1987 doi:10.1111/j.1537-2995.2010.02720.x
Sun JM et al. 2015; Pediatric Research 2015; 78:712–716 doi:10.1038/pr.2015.161
Cord Blood Education
Within the United States, healthcare providers can order shipments of our printed parent brochures for free in both English and Spanish. Parent's Guide to Cord Blood Foundation has developed educational brochures for parents that cover both public donation and private banking in a balanced way. Our brochures are available for download from cordbloodeducation.org in over a dozen languages and dialects, with the content adjusted to the national situation in different countries. These brochures were approved by our Scientific and Medical Advisory Panel and within the United States they are updated annually to adjust prices and include new clinical trials.
Our Foundation has also developed several Fact Sheets for medical professionals that are available for download from doctorsguidecordblood.org.
We are the world's only organization dedicated to cord blood education that can claim all of the following:
- we are incorporated as a non-profit,
- we cover both public donation and private storage in a balanced way,
- our content is written by scientists,
- we are supervised by an Advisory Panel of leading scientists and physicians,
- and we are accredited by Health on the Net Foundation (HON).
Our website contains numerous unique cord blood resources:
- World's most complete directory of family banks
- World's most complete directory of public banks
- World's only complete searchable maps of family banks, public banks, FACT banks, AABB banks
- Within the United States, the only complete searchable map of hospitals accepting cord blood donations
Health on the Net Foundation (HON) is an international non-profit under the United Nations that is dedicated to inspecting and accrediting medical websites for accurate and ethical content. Parent's Guide to Cord Blood Foundation is the only cord blood organization that is currently accredited by HON, and we have been continuously accredited since May 2001.
Websites accredited under the HON code are committed to abide by these 8 principles:
- Authority - Give qualifications of authors
- Complementarity - Information to support, not replace physician
- Confidentiality - Respect the privacy of site users
- Attribution - Cite the sources and dates of medical information
- Justifiability - Justification of claims / balanced and objective claims
- Transparency - Accessibility, provide valid contact details
- Financial disclosure - Provide details of funding
- Advertising - Clearly distinguish advertising from editorial content
Congress commissioned an Institute of Medicine study on the ideal structure of a national cord blood program. Based on the IoM report, Congress passed the Stem Cell Therapeutic and Research Act of 2005 that was signed into law 20 Dec. 2005. The key language regarding education is the requirement: Information provided to the maternal donor regard(s) all of her medically appropriate cord blood options. ie: Education of expectant parents and Informed Consent of maternal donors should cover all options, not just donation.
Cord Tissue Banking
The term "cord tissue" refers to the rest of the umbilical cord, other than the blood. A normal umbilical cord contains one artery, two veins, an outer skin, and it is filled with a gelatinous material called Wharton’s Jelly. Umbilical cords can vary widely in length, but the average cord is about 61 cm (24 inches) long and weighs 40 gm.
Percy Malpas 1964; British Medical Journal 1:673–674.
Like cord blood, the umbilical cord itself is a rich source of stem cells. However, they are a different population of stem cells, which immediately suggests there is value to storing both the cord blood stem cells and the cord tissue stem cells. While most of the stem cells in cord blood are blood-forming or hematopoietic stem cells (HSC), most of the stem cells in cord tissue are mesenchymal stem cells (MSC). The MSC are not distributed uniformly in the cord, but are mostly clustered around the walls of the blood vessels. The typical umbilical cord is estimated to hold 11 million progenitor cells per gram of tissue.
Schugar RC et al. 2009; Journal of Biomedicine and Biotechnology 2009:789526 (open access) doi:10.1155/2009/789526
Cord blood banking has become mostly standardized over the past 25 years, but cord tissue banking is still an evolving field and industry standards are still being developed. For example, in cord blood banking the standard method of processing is to separate the component of the blood that holds stem cells and cryogenically freeze the isolated cells.
Since 2015, half of family cord blood banks are also offering cord tissue storage, but their methods differ widely. Some banks merely freeze the cord intact with no attempt to process it. The majority of banks that offer cord tissue banking do process the cord, but the final biological product that they store may be either a tissue product (for example very small pieces of cord), or a cellular product of isolated cells (the same as cord blood storage), or both. The Parent’s Guide to Cord Blood Foundation is working to develop educational materials to help both parents and professionals navigate this rapidly evolving field.
Pedro Silva Couto 2014; Storage of Mesenchymal Stem/Stromal cells in family stem cell banks: What do they offer? Parent's Guide to Cord Blood newsletter May 2014
Parent's Guide to Cord Blood Foundation 2015; Cord Blood Industry Report 2015
Parent's Guide to Cord Blood Foundation 2016; poster #1606 at International Cord Blood Symposium, Transfusion doi:10.1111/trf.13686
Just like cord blood banking for the family, cord tissue banking is a form of biological insurance, where parents bank their baby’s stem cells for future therapies. The two main benefits of cord tissue banking are to have more stem cells from the same child and to have different types of cells. There is a great deal of current research on potential therapies with stem cells from the cord tissue and the placenta, either alone or together with cord blood stem cells. Parents who have more cells in storage will have more options in the future.
Perinatal Stem Cells 2nd edition 2013; book published by Wiley