cord blood banking cbr | collection and preservation of cord blood for personal use

The American Pediatric Association in 2008 recommended that physicians recommend that cord blood be donated instead of saved privately for family families. One of the major proponents for this was Joanne Kurtzberg, who profited from this by getting funding for her public cord blood bank at Duke University. She has since started her own private cord blood bank after doing more research on Cerebral Palsy. Interesting.
While many diseases can be treated with a cord blood transplant, most require stem cells from another donor (allogeneic).  Cord blood cells taken from the patient (autologous) typically contain the same defect or precancerous cells that caused the patient to need the transplant in the first place.  Most medical professionals believe the chance that cord blood banking will be utilized by the patient or a close relative is relatively low.  Estimates range from 1 out of 1,000 to 1 out of 200,000.[2]  From these estimates, privately stored cord blood is not likely to be utilized by the average family. The American Academy of Pediatrics has discouraged cord blood banking for self-use, since most diseases requiring stem cell transplants are already present in the cord blood stem cells.[3] Additionally, a recent study published in Pediatrics indicates that few transplants have been performed using privately stored cord blood.  From the responses of 93 transplant physicians, in only 50 cases was privately banked blood used.  In 9 of these cases the cord blood was transplanted back into the donor patient (autologous transplant).[4]  One of the main selling points of private cord blood banks is the possibility of a future  autologous transplant. 
Life Line Stem Cell asks mothers arriving for delivery to donate all perinatal tissue: cord blood, cord tissue, and the placenta. Cord blood donations that are eligible for transplant are sent to a public cord blood bank; the tissue collections go towards research programs.
Banked cord blood is most abundant in white blood cells and stem cells. While a lot of attention is paid to the stem cells, there are approximately 10 times more total nucleated cells (TNCs) than stem cells in any cord blood collection. TNCs are basically white blood cells, or leukocytes; they are the cells of the immune system that protect the body. Despite stem cells comprising one-tenth of most collections, cord blood is still considered a rich source of hematopoietic (he-mah-toe-po-ee-tic) stem cells (HSCs). HSCs are often designated by the marker CD34+. Hematopoietic stem cells can become two categories of cells: myeloid and lymphoid cells. Myeloid cells go on to form your red blood cells, platelets, and other cells of the blood. Lymphoid cells go on to become the B cells and T cells and are the basis for the immune system. Cord blood also contains mesenchymal (meh-sen-ki-mal) stem cells (MSCs), but they are much more abundant in cord tissue, which we will discuss in a minute.
Haematopoietic stem cells (HSCs) can make every type of cell in the blood – red cells, white cells and platelets. They are responsible for maintaining blood production throughout our lives. They have been used for many years in bone marrow transplants to treat blood diseases.
Banking a baby’s blood and stem cells in a cord blood bank is a type of insurance. Ideally, you would not need to access your baby’s stem cells in order to address a medical concern. However, using a cord blood bank can provide peace of mind in knowing that you have a valuable resource if you need it.
Your baby’s cord blood could be a valuable resource for another family.  From foundations to non-profit blood banks and medical facilities, there are numerous locations that will collect, process, and use the stem cells from your baby’s cord blood to treat other people.
In addition to the use of cord blood stem cells for transplantation, cord blood stem cells are currently being investigated for use in stem cell therapy.  Cord blood stem cells are multipotent and are believed to have greater plasticity (the ability to form into different stem cell types) than adult hematopoietic stem cells found in bone marrow.  HSCs are being investigated for use in autoimmune diseases such as diabetes, rheumatoid arthritis, and systemic lupus erythermatosis (SLE) in order to reprogram or reconstitute the immune system.  Additionally, research is being conducted on differentiating HSCs into other tissue types such as skeletal and cardiac muscle, liver cells (hepatocytes), and neurons.   HSCs are currently being used in gene therapy, due to their self-renewing properties, as a means of delivering genes to repair damaged cells.  HSCs are the only cells currently being used in this manner in clinical gene therapy trials.
There is no cost associated with public cord blood banking, but you do give up your rights to your baby’s stem cells at the time of donation. The public cord blood bank owns the donation. If your child or another family member needs a transplant in the future, there is no guarantee you would have access to your baby’s cord blood.
Blood from the umbilical cord and placenta is put into a sterile bag. (The blood is put into the bag either before or after the placenta is delivered, depending upon the procedure of the cord blood bank.)
“This reanalysis supports several previously expressed opinions that autologous [to use one’s OWN cells] banking of cord blood privately as a biological insurance for the treatment of life-threatening diseases in children and young adults is not clinically justified because the chances of ever using it are remote. The absence of published peer-reviewed evidence raises the serious ethical concern of a failure to inform prospective parents about the lack of future benefit for autologous cord banking … Attempts to justify this [commercial cord blood banking] are based on the success of unrelated public domain cord banking and allogeneic [using someone ELSE’S cells] cord blood transplantation, and not on the use of autologous [the person’s OWN cells] cord transplantation, the efficacy of which remains unproven”.
Of course, this means that expectant parents will have one more choice to make about their child’s health and future. “I certainly don’t think parents should feel guilty if they don’t privately bank their child’s blood,” Dr. Kurtzberg says. The best choice is the one that works for your family.
Like most transplants, the stem cells must be a genetic match with the patients to be accepted by the body’s immune system. It goes without saying that a patient’s own cord blood will be a 100% match. The second highest chance of a genetic match comes from siblings.
Prior to freezing the cells, samples are taken for quality testing. Banks measure the number of cells that are positive for the CD34 marker, a protein that is used to estimate the number of blood-forming stem cells present. Typical cost, $150 to $200 per unit. They also measure the number of nucleated cells, another measure of stem cells, both before and after processing to determine the cell recovery rate. Typical expense, $35 per unit. A portion of the sample is submitted to check that there is no bacterial or fungal contamination. Typical expense, $75 per unit. Public banks will also check the ability of the sample to grow new cells by taking a culture called the CFU assay. Typical expense, $200 to $250 per unit.
Today, many conditions may be treatable with cord blood as part of a stem cell transplant, including various cancers and blood, immune, and metabolic disorders. Preserving these cells now may provide your family potential treatment options in the future.
In Europe, Canada, and Australia use of cord blood is regulated as well.[5] In the United Kingdom the NHS Cord Blood Bank was set up in 1996 to collect, process, store and supply cord blood; it is a public cord blood bank and part of the NHS.[7]
Florida Hospital for Children is conducting an FDA-regulated phase I clinical trial to investigate the use of a child’s stem cells derived from their own cord blood as a treatment for acquired sensorineural hearing loss.
Private cord blood banks allow families to store cord blood stem cells for themselves and their loved ones. They are privately funded, and typically charge a first-year processing fee that ranges from about $1,400 to $2,300, plus annual storage costs of about $115 to $175. (Americord offers cord blood banking for a one-time fee of $3,499, which includes 20 years of storage). The pros and cons of private cord blood banking are listed below.
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Cord blood donation doesn’t cost anything for parents. Public cord blood banks pay for everything which includes the collection, testing, and storing of umbilical cord blood. This means that cord blood donation is not possible in every hospital.
The cord blood collection process is simple, safe, and painless. The process usually takes no longer than five minutes. Cord blood collection does not interfere with delivery and is possible with both vaginal and cesarean deliveries.
Generally, cord blood can only be used to treat children up to 65 lbs. This is because there simply aren’t enough stem cells on average in one unit of cord blood to treat an adult.  Through our Cord Blood 2.0 technology, we have been able to collect up to twice as many stem cells as the industry average.  Getting more stem cells increases the chance of being able to treat someone later in life.
Cord blood contains mesenchymal stem cells but is much more abundant in hematopoietic stem cells. Cord tissue, on the other hand, contains some hematopoietic stem cells but is much richer in mesenchymal stem cells. Cord tissue, or Wharton’s jelly, is the protective layer that covers the umbilical cord’s vein and other vessels. Its MSCs can become a host of cells including those found in the nervous system, sensory organs, circulatory tissues, skin, bone, cartilage, and more. MSCs are currently undergoing clinical trials for sports injuries, heart and kidney disease, ALS, wound healing and autoimmune disease. As with cord blood, cord tissue is easily collected at the type of birth and holds great potential in regenerative medicine. Learn more about cord tissue banking here.
Up to 180 mL of blood can be taken from an umbilical cord for use in stem cell transplants.  Due to the experimental nature of cord blood transplants, such transplants are considered on a case-by-case basis.  This blood is collected from the umbilical cord, processed,[1] and cryogenically preserved shortly after the umbilical cord is clamped. This blood can be cryogenically preserved for public or private (family) use.  Public registries store cord blood donated for availability to the general public for transplantation.  Private registries store cord blood on behalf of families who wish to use this blood for the donor infant, siblings, or other family members.  Private cord blood banks charge a collection fee (ranging from $1,000-2,000) and an annual storage fee (approximately $150 per year).
Your baby isn’t the only one who may benefit from having access to preserved newborn stem cells. The cells can potentially be used by siblings and parents, too. In many cord blood treatments, stem cells from a matched family member are preferred.
Banking of stem cells from cord blood began in 1994 with the foundation of the New York Blood Centre Cord Blood Bank. The field of umbilical cord blood storage has matured considerably over the last two decades. We continue to learn more about the long-term effects of cryo-preservation on the cells, which has resulted in increased storage times.
Your baby’s newborn stem cells are transported to our banking facilities by our medical courier partner, and you can receive tracking updates. Each sample is processed and stored with great care at our laboratory in Tucson, Arizona. CBR’s Quality Standard means we test every cord blood sample for specific quality metrics.
Collected cord blood is cryopreserved and then stored in a cord blood bank for future transplantation. Cord blood collection is typically depleted of red blood cells before cryopreservation to ensure high rates of stem cell recovery.[4]
There are several cord blood banks that are accredited by the American Association of Blood Banks. Most offer information on cord blood banking and provide private cord blood banking services. With a little research, you should be able to locate a credible cord blood bank online.
Cord blood cannot be used if the donor (baby) contains the same genetic illness as the recipient. Most cord blood banks glaze over this, but it is important to understand that the odds of using cord blood for the same child are much lower than the odds of using them for a sibling.
The Stem Cell Therapeutic and Research Act was passed in 2005, which supports building a public reserve of 150,000 cord blood units from ethnically diverse donors in order to treat more than 90% of patients in need of HSC transplants.  Donors from ethnic minority patients are particularly in need due to the greater variation of HLA-types in non-Caucasian ethnicities. Thirty-five percent of cord blood units go to patients of diverse ethnic and racial backgrounds.
Cord blood in public banks is available to unrelated patients who need haematopoietic stem cell transplants. Some banks, such as the NHS bank in the UK, also collect and store umbilical cord blood from children born into families affected by or at risk of a disease for which haematopoietic stem cell transplants may be necessary – either for the child, a sibling or a family member. It is also possible to pay to store cord blood in a private bank for use by your own family only.
Generally not. The reason siblings are more likely to match is because they get half of their HLA markers from each parent. Based on the way parents pass on genes, there is a 25 percent chance that two siblings will be a whole match, a 50 percent chance they will be a half match, and a 25 percent chance that they will not be a match at all. It is very rare for a parent to be a match with their own child, and even more rare for a grandparent to be a match.
If you make a donation to a public cord blood bank, you can’t reserve it for your family, so it may not be available for your future use. Both the American Academy of Pediatrics (AAP) and American Medical Association (AMA) recommend public cord blood banking over private cord blood banking. Here’s why:
While banking cord blood is a new experience for many parents, it is a simple one. After all, most mothers are worried about how the delivery will go and don’t want to also be worried about the details of collecting, processing and cryo-preserving their babies’s cord blood. Thankfully, the healthcare provider and the cord blood bank do most of the work. Here are the steps found in cord blood banking:
The majority of programs that accept cord blood donations require the mother to sign up in advance. In the united States, the current requirement is to sign up by the 34th week of pregnancy. This cannot be over-stressed; time and time again, mothers who want to donate are turned away because they did not inquire about donation until it was too late.
There are some hospitals that have dedicated collections staff who can process mothers at the last minute when they arrive to deliver the baby. However, in the United States that is the exception to the rule.
Though uses of cord blood beyond blood and immunological disorders is speculative, some research has been done in other areas.[17] Any such potential beyond blood and immunological uses is limited by the fact that cord cells are hematopoietic stem cells (which can differentiate only into blood cells), and not pluripotent stem cells (such as embryonic stem cells, which can differentiate into any type of tissue). Cord blood has been studied as a treatment for diabetes.[18] However, apart from blood disorders, the use of cord blood for other diseases is not in routine clinical use and remains a major challenge for the stem cell community.[17][18]
The University of Texas Health Science Center at Houston is conducting a pioneering FDA-regulated phase I/II clinical trial to compare the safety and effectiveness of two forms of stem cell therapy in children diagnosed with cerebral palsy. The randomized, double-blinded, placebo-controlled study aims to compare the safety and efficacy of an intravenous infusion of autologous cord blood stem cells to bone marrow stem cells.
Cord blood is currently approved by the FDA for the treatment for nearly 80 diseases, and cord blood treatments have been performed more than 35,000 times around the globe to treat cancers (including lymphoma and leukemia), anemias, inherited metabolic disorders and some solid tumors and orthopedic repair. Researchers are also exploring how cord blood has the ability to cross the blood–brain barrier and differentiate into neurons and other brain cells, which may be instrumental in treating conditions that have been untreatable up to this point. The most exciting of these are autism, cerebral palsy and Alzheimer’s.
No one knows how stem cells will be used in the future, but researchers hope that they may be used to treat many conditions, like Alzheimer’s, diabetes, heart failure, spinal cord damage, and other conditions.

5 Replies to “cord blood banking cbr | collection and preservation of cord blood for personal use”

  1. Dennis Michael Todd, PhD, joined Community Blood Services as its President and CEO in 2000. Community Blood Services operates the NJ Cord Blood Bank and The HLA Registry bone marrow donor center, both of which are affiliated with the National Marrow Donor Program (NMDP). In 2012, the blood center expects to distribute over 85,000 units of red cells and 20,000 platelets to hospitals and medical centers throughout northern NJ and Orange County, NY. Dr. Todd is presently a member of the NMDP Executive Committee and Chairman of the Finance Committee. He is a member of the International Society for Cellular Therapy (ISCT), the International Society for Stem Cell Research (ISSCR), the AABB, the American Association of Bioanalysts, and the New Jersey Society of Blood Bank Professionals.
    If you or your spouse or partner has a family history of a disease that is treatable with stem cells, or if a family member is currently in need of a stem cell transplant, private cord blood banking could be the right choice for you. To read more reasons to consider private cord blood banking, click here.
    Bone marrow and similar sources often requires an invasive, surgical procedure and one’s own stem cells may already have become diseased, which means the patient will have to find matching stem cells from another family member or unrelated donor. This will increase the risk of GvHD. In addition, finding an unrelated matched donor can be difficult, and once a match is ascertained, it may take valuable weeks, even months, to retrieve. Learn more about why cord blood is preferred to the next best source, bone marrow.
    Stem Cell Storage is not included in their price. Viacord and Cord Blood Registry both charge for annual storage. This means that when you pay for your initial cord blood and/or cord tissue storage you will also have to pay annually for storage.
     In the procurement of embryonic stem cells for research, the embryo from which the cells are harvested is destroyed.  For those who believe that human life begins at conception this research is obviously unethical.  In contrast, adult stem cells can be isolated from tissue from a consenting patient.  While cord blood stem cells are classified as adult stem cells, they appear to have greater potency (ability to differentiate into other cell types) than other adult stem cells, making them a potentially valuable option for use in a variety of treatments and therapies.   Cord blood stem cells offer some of the advantages of ESCs without any of the ethical drawbacks.   Research into the use of cord blood stem cells for the treatment of disease and disability is a promising and ethical avenue of stem cell research.
    In the United States, the Food and Drug Administration regulates any facility that stores cord blood; cord blood intended for use in the person from whom it came is not regulated, but cord blood for use in others is regulated as a drug and as a biologic.[6] Several states also have regulations for cord blood banks.[5]
    Umbilical cord blood is blood that remains in the placenta and in the attached umbilical cord after childbirth. Cord blood is collected because it contains stem cells, which can be used to treat hematopoietic and genetic disorders.
    Cord Blood Registry is a registered trademark of CBR® Systems, Inc.  Annual grant support for Parent’s Guide to Cord Blood Foundation is made possible by CBR® through the Newborn Possibilities Fund administered by Tides Foundation.
    Tissue typed and listed on the registry of the C.W. Bill Young Cell Transplantation Program, also called the Be The Match Registry®. (The registry is a listing of potential marrow donors and donated cord blood units. When a patient needs a transplant, the registry is searched to find a matching marrow donor or cord blood unit.)
    Collected cord blood is cryopreserved and then stored in a cord blood bank for future transplantation. Cord blood collection is typically depleted of red blood cells before cryopreservation to ensure high rates of stem cell recovery.[4]

  2. Hello everyone and welcome to Cord-Blood.org website! On this page, you will learn in a short what is cord-blood.org website about. First, and probably the most important thing to make clear, is that Cord-Blood.org website is not in anyway associated, affiliated, or partnered with any…
    And as Victor and Tracey Dones learned, a child’s own cord blood can’t always be used to treat him, even when he’s young. “Childhood leukemia is one of the diseases private banks like to play up, but most kids with leukemia are cured with chemotherapy alone. If a transplant is needed, we wouldn’t use a child’s tainted cord blood,” Dr. Kurtzberg says.

  3. Congratulations to the Marepalli family, this week’s winners of a free year of storage! CBR Clients: Enter for a chance to win by tagging a family photo with #CBRFamilyContest! #MyStemCellsLiveAtCBR pic.twitter.com/RLIx54bLqS
    The cord blood of your baby is an abundant source of stem cells that are genetically related to your baby and your family. Stem cells are dominant cells in the way they contribute to the development of all tissues, organs, and systems in the body.
    It depends on who you ask. Although commercial cord blood banks often bill their services as “biological insurance” against future diseases, the blood doesn’t often get used. One study says the chance that a child will use their cord blood over their lifetime is between 1 in 400 and 1 in 200,000.
    The therapeutic potential of stem cells from the umbilical cord is vast. Cord blood is already being used in the treatment of nearly 80 life-threatening diseases2, and researchers continue to explore it’s potential. Duke University Medical Center is currently using cord blood stem cells in a Phase II clinical trial to see if it benefits kids with Autism. The number of clinical trials using cord tissue stem cells in human patients has increased to approximately 150 since the first clinical trial in 2007. Cord tissue stem cells are also being studied for the potential use in kids with Autism – a Phase I Clinical Trial is underway.
    Georgia Regents University is conducting an FDA-regulated phase I/II clinical trial to assess whether an infusion of autologous stem cells derived from their own cord blood can improve the quality of life for children with cerebral palsy.
    If you feel that the procedure is too expensive for your child, check with the hospital to see if there are any programs and/or grants available that can assist with the procedure.  Some companies do offer financial aid.
    The main reason for this requirement is to give the cord blood bank enough time to complete the enrollment process. For the safety of any person who might receive the cord blood donation, the mother must pass a health history screening. And for ethical reasons, the mother must give informed consent.

  4. CBR was the first family bank accredited by AABB (formerly the American Association of Blood Banks) and the company’s quality standards have been recognized through ISO 9001:2008 certification—the global business standard for quality. The Federal Drug Administration (FDA) has issued cord blood regulations, and the states of California, Illinois, Maryland, New York and New Jersey have mandatory licensing for cord blood banking. The stringent laboratory processes, record keeping, quality control and quality assurance of CBR are designed to meet all federal and state guidelines and regulations.
    Blood in the umbilical cord and placenta is rich with blood-forming stem cells that can help save the lives of patients with diseases and disorders such as leukemia, lymphoma and aplastic anemia. With your consent, Canadian Blood Services can collect cord blood when you deliver your baby for Canadian Blood Services’ Cord Blood Bank—to be used by anyone who needs stem cell treatment.
    || Payment Plan Disclosures for CareCredit 48-Month Plan – Availability subject to credit approval. $1,650 or as low as $46 per month. If you pay only the minimum amount it will take you 48 months to pay off the balance and $2,201 total. A 14.90% Extended Payment Plan for 48 Months on purchases of $1,000 or more with your CareCredit card. Fixed minimum monthly payments required. Penalty APR may apply if you make a late payment. On promo purchase, fixed monthly payments equal to 4.8439% of initial purchase balance for 24 months; 3.4616% of initial purchase balance for 36 months; 2.7780% of initial purchase balance for 48 months required, and interest charges will be applied to promo balance at a reduced 14.90% APR if (1) promo purchases paid in full in promotion duration as indicated, and (2) all minimum monthly payments on account paid when due. Purchase APR of up to 29.99% applies to expired promotions and optional charges.
    In this way, cord blood offers a useful alternative to bone marrow transplants for some patients. It is easier to collect than bone marrow and can be stored frozen until it is needed. It also seems to be less likely than bone marrow to cause immune rejection or complications such as Graft versus Host Disease. This means that cord blood does not need to be as perfectly matched to the patient as bone marrow (though some matching is still necessary).
    Cord blood can’t be used to treat everything. If your child is born with a genetic condition such as muscular dystrophy or spina bifida, then the stem cells would have that condition, says Dr. Kurtzberg. But if the cord blood donor is healthy and there is a sibling or another immediate family member who has a genetic condition, the cord blood could be a good match for them.
    Upon arrival at CBR’s laboratory, the kit is immediately checked in and inspected. Next, the cord blood unit is tested for sterility, viability, and cell count. In addition, the cord tissue is tested for sterility. CBR processes cord blood using the AutoXpress® Platform* (AXP®) – a fully automated, functionally closed stem cell processing technology. The AXP platform is an integral component of CBR’s proprietary CellAdvantage® system. CBR has the industry’s highest published average cell recovery rate of 99%.
    In Europe and other parts of the world, cord blood banking is more often referred to as stem cell banking. As banking cord blood is designed more to collect the blood-forming stem cells and not the actual blood cells themselves, this term may be more appropriate.
    The syringe or bag should be pre-labeled with a unique number that identifies your baby. Cord blood may only be collected during the first 15 minutes following the birth and should be processed by the laboratory within 48 hours of collection.
    The AMA also suggests considering private cord blood banking if there is a family history of malignant or genetic conditions that might benefit from cord blood stem cells. Keep in mind, however, that to find a suitable match for any type of transplant, 70% must look outside their family.

  5. ^ a b c American Academy of Pediatrics Section on Hematology/Oncology; American Academy of Pediatrics Section on Allergy/Immunology; Lubin, BH; Shearer, WT (January 2007). “Cord blood banking for potential future transplantation”. Pediatrics. 119 (1): 165–70. doi:10.1542/peds.2006-2901. PMID 17200285.
    Cord blood does not have to be as closely matched as bone marrow or peripheral blood transplants. Bone marrow transplants typically require a 6/6 HLA match.  While a closely matched cord blood transplant is preferable, cord blood has been transplanted successfully with as few as 3/6 matches.  For patients with uncommon tissue types, cord blood may be an option if a suitable adult donor cannot be found.  Since cord blood is cryogenically preserved and stored, it is more readily available than bone marrow or peripheral blood from an unrelated donor, allowing transplants to take place within a shorter period of time.  It takes approximately two weeks to locate, transfer, and thaw a preserved cord blood unit.  Finding a suitable bone marrow donor typically takes at least two months.
    Gift of Life is a non-profit charity that seeks to help Jewish patients find a transplant match.  They recruit both bone marrow donors and cord blood donations from the Jewish community.  Gift of Life operates their own accredited cord blood laboratory that participates in the national NMDP network.
    When it comes to cord blood banking, expectant parents have three options: (1) They can privately store their cord blood for their family, (2) They can take the public option and donate their cord blood for other families, or (3) They can do nothing, at which point the medical facility must dispose of the cord blood as medical waste. At Cryo-Cell International, we believe cord blood should not be discarded. Many states agree with our basic sentiment and have passed laws or guidelines for physicians to use when discussing private and public banking options with expectant parents.
      There are many “what if” situations that we all consider in our life. One of the most serious is “What if a child or other family member was to become seriously ill?” Cord Blood Banking clinics have been growing exponentially in response to this…
    A limitation of cord blood is that it contains fewer HSCs than a bone marrow donation does, meaning adult patients often require two volumes of cord blood for treatments. Researchers are studying ways to expand the number of HSCs from cord blood in labs so that a single cord blood donation could supply enough cells for one or more HSC transplants.
    In Europe and other parts of the world, cord blood banking is more often referred to as stem cell banking. As banking cord blood is designed more to collect the blood-forming stem cells and not the actual blood cells themselves, this term may be more appropriate.
    [3] American Academy of Pediatrics Section on Hematology/Oncology, American Academy of Pediatrics Section on Allergy/Immunology, Bertram H. Lubin, and William T. Shearer, “Cord Blood Banking for Potential Future Transplantation,” Pediatrics 119 (2007): 165-170.

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