Definitions & Overview: Umbilical Cord Blood
The umbilical cord connects an unborn baby to the placenta. The umbilical cord pumps oxygen and nutrient rich blood from the placenta to the baby, and brings back the oxygen and nutrient depleted blood to the placenta once it has circulated through the baby’s body. It contains one vein, which brings the blood from the placenta to the baby, and two arteries, which bring the blood back from the baby to the placenta. The tissue surrounding these umbilical cord vessels is called “Wharton’s jelly”. The placenta, umbilical cord, and the blood in both are all genetically identical to the baby, not the mother.
Cord blood is the blood that remains in the umbilical cord and placenta after a baby is born and the cord is cut, separating the baby from the mother. This blood is the baby’s blood.
The cord blood can be safely and easily collected and stored for future medical use whether a baby is born via vaginal delivery or caesarian section (C-section).
There is absolutely no risk or pain to the mother or baby involved in collection of cord blood. Collection takes place after the baby is born and does not in any way interfere with the birth.
The obstetrician or midwife overseeing the delivery can easily collect the cord blood using a kit provided in advance. After cleaning the umbilical cord, the cord blood is collected into a sterile bag and sent to a laboratory for processing.
Umbilical cord blood can be frozen and cryopreserved for more than 20 years (and possibly much longer), and thawed with the efficient recovery of HSCs that are suitable for transplant and able to engraft and repopulate the blood and immune system. 1,24
The optimal method for freezing and storing the cells is to combine the sample with a cryoprotectant and to slowly cool and freeze the sample at a controlled rate. This protects the cells from the damage that freezing can cause and maximizes their viability during the freezing process. 21 Once frozen, the sample is transferred for long-term storage in vapor or liquid nitrogen.
|Accreditation||Public and private cord blood and tissue banks can receive accreditation from accrediting bodies such as the American Association of Blood Banks (AABB) and the Foundation for the Accreditation of Cellular Therapy (FACT). Accreditation demonstrates that the bank meets a set of standards for collection, processing and storage, and undergoes periodic inspections and re-accreditation, which can provide assurances of quality methods, materials, and practices.|
|Cord blood and tissue stem cell matching||
A child will be a perfect match for its own banked cord blood or tissue stem cells. Siblings and other immediate family members could be at least a partial match for the baby’s HSCs and thus also potentially benefit from cord blood stored in a family bank in the case of future need. A sibling has a 25% chance of being a perfect match, a 50% chance of being a partial match, and a 25% chance of not matching at all. The biological parents of a baby will always be a partial match, as the egg and sperm each contribute half of the baby’s DNA.
|Engraftment||Following HSC transplant, the successful mobilization of the stem cells to the patient’s bone marrow, where they take up residence and begin to differentiate into the various cell types that make up the blood and immune systems.|
|FDA||United States Food and Drug Administration; all public and private cord blood and tissue banks in the U.S. must register with the FDA.|
|Graft-versus-host disease (GvHD)||
This occurs when the donor hematopoietic stem cells are transplanted into a recipient, and the donor immune cells in the graft see the body’s own cells as foreign, triggering an immune reaction that can cause severe and sometimes chronic symptoms, including organ damage. GvHD is less likely to occur (and if it occurs to be less severe) the closer the match between the donor and recipient. It of course does not happen if the patient gets back his own cells.
|Hematopoietic stem cell transplant||
The purpose of a HSC transplant is to replace the blood and immune cell populations of a patient suffering from a blood cancer or other blood disorder. To do this, the blood/immune-forming cells in the patient’s bone marrow are destroyed using high-dose chemotherapy and radiation, and the bone marrow is repopulated with healthy HSCs via a transplant procedure using either a patient’s own HSCs (collected in advance) or donor HSCs depending on the disease being treated and other circumstances.
|Hematopoietic stem cells (HSCs)||
Immature, blood-forming (hematopoietic) progenitor cells that are the building blocks of all the different types of hematopoietic cells. They have the potential to mature and differentiate to form the various types of cells that make up the human blood and immune systems. HSCs are present in bone marrow, peripheral blood, and cord blood.
Matching of human leukocyte (white blood cell) antigens between donor and recipient is performed to determine the suitability of a cord blood or tissue sample for transplant. Six specific HLAs are typically tested to identify a perfect or partial match.
If a donor and recipient have identical antigens at all six HLA sites tested (6/6), the cord blood sample is considered to be a perfect match. If the donor and recipient have the same antigens at three specific HLA sites (HLA-DR, HLA-B, and HLA-A) or alternatively, at four or five of the six HLAs tested, the donor tissue is considered to be a partial match.
|Human leukocyte antigen (HLA) system||
Human leukocyte antigens are molecules on the surface of cells that help the body’s immune system distinguish its own cells from foreign cells, such as bacteria and other infectious microorganisms or cancer cells. Whether or not a donor cord blood or tissue sample is suitable for transplant in potential recipient is determined based on HLA matching.
|Investigational New Drug (IND)||The U.S. FDA issues an IND application to allow an exemption for use of a non-commercial drug product for therapeutic applications. A cord blood or tissue sample stored at a private (and in some cases also at a public) bank requires an IND for use in a transplant procedure.|
|Major histocompatibility complex (MHC)||
HLAs make up the major histocompatibility complex. MHC class I and II antigens are the most immunogenic — that is, the most likely to cause rejection of donor tissue. Among these, six HLAs in particular are typically tested to determine if a donor cord blood sample is a suitable match for transplant into a recipient.
|Mesenchymal stem cells (MSCs)||
The stem cells isolated from umbilical cord tissue. These are non-hematopoietic adult stem cells. In the developing embryo, MSCs are precursors for many different types of cells in the body. MSCs are present in almost all types of tissues and organs. In the laboratory, human MSCs have been shown to be able to mature to form osteocytes (bone cells), chondrocytes (cartilage), adipocytes (fat cells), hepatocytes (liver cells), pancreatic cells (islet cells that produce insulin), and neuronal cells. Hundreds of clinical trials worldwide are evaluating the potential for MSC-based cell therapy to treat a variety of diseases and for tissue repair and regenerative medicine.
|Private cord blood and tissue banks||A private bank collects cord blood and cord tissue at the time you deliver your baby, at the hospital of your choice, any day and any time. The sample is sent to the laboratory for processing and storage. Cord blood that you store in a private bank is reserved for your exclusive use and is available to you at any time.|
|Public cord blood banks||
Cord blood donated to a public bank is available to anyone who may need it and you are not able to reserve it for your child or family members. Public banks do not charge to collect, process, or store cord blood. If you need to retrieve your sample, or another donor’s sample from a public bank in the future, retrieval typically costs about $30,000. Public banks discard 50-80% of the cord blood samples donated due to poor results on quality testing of the sample or insufficient numbers of stem cells.
|Umbilical cord blood||The umbilical cord connects an unborn baby to the placenta. Through the umbilical cord, the baby receives oxygen and nourishment from the mother throughout the pregnancy. Cord blood is the blood that remains in the umbilical cord and placenta after a baby is born and the cord is cut, separating the baby from the mother. It contains hematopoietic stem cells (HSCs) that have therapeutic value.|
|Umbilical cord tissue||
Cord tissue is made up of the tissue and cells that surround the blood vessels in the umbilical cord. Like cord blood, cord tissue also contains stem cells with potential medical uses; these are called mesenchymal stem cells (MSCs).
Why is cord blood important, what is its value and why do people bank it?
Cord blood contains hematopoietic stem cells (HSCs). These are immature, blood-forming (hematopoietic) progenitor cells that are the cells that divide to create all of the different types of hematopoietic cells found in the bone marrow. They have the potential to mature and differentiate to form the various types of cells that make up the human blood and immune systems. HSCs are only present in bone marrow, peripheral blood, and cord blood. Cord blood has, by far, the highest concentration of HSC’s.
HSCs are able to reconstitute the human hematopoietic system when it has been damaged or destroyed by disease, chemotherapy, or radiation. Cord-blood derived HSCs have been used successfully in transplants to treat various blood diseases and cancers since 1988. According to estimates, more than 30,000 cord blood transplants have been performed to treat children and adults with at least 80 different blood, immune, and bone diseases. C Transplants in children using umbilical cord blood-derived HSCs have achieved comparable or better survival outcomes compared to bone marrow-derived HSC transplants, and the results using cord blood to treat adults are continuing to improve. C,Q
Evidence shows several advantages to using cord blood for HSC transplants as their more primitive, immature nature makes them less likely to provoke an immune reaction in the recipient. A Cord blood HSC transplants may not require as close a “match” between donor and recipient as would HSCs derived from bone marrow or peripheral blood. A Cord blood-derived stem cell transplants also tend to cause fewer side effects and require fewer transplant medications compared to bone marrow transplants.
Researchers are continually discovering new ways to use cord blood stem cell transplants to treat an ever-increasing number and scope of disorders. In addition to blood and immunodeficiency diseases, and cancers, treatable conditions now include autoimmune disorders, and genetic and metabolic diseases. Because of this rapid expansion in the number and type of diseases treated by cord blood, it is impossible to predict the full scope of potential future therapeutic uses for cord blood stem cell transplants.
Examples of Diseases Being Treated with Cord Blood Transplant
Leukemias Severe combined immunodeficiency (SCID)
Lymphomas Purine nucleoside phosphorylase deficiency
Multiple myeloma Reticular dysplasia
Hodgkin’s disease Wiskott-Aldrich syndrome
Retinoblastoma Ataxia telangiectasia
Neutropenias DiGeorge syndrome
Solid tumors Kostmann syndrome
Chronic granulomatous disease
Adenosine deaminase deficiency
Leukocyte adhesion deficiency
Blood disorders: Metabolic disorders:
Sickle cell anemia Adrenoleukodystrophy
Thalassemia Krabbe disease
Aplastic anemia Hunter syndrome
Fanconi anemia Hurler syndrome
Diamond-Blackfan anemia Sanfilippo syndrome
Amegakaryocytosis thrombocytopenia Lesch-Nyhan syndrome
Mucolipidosis Type II, III
Niemann Pick syndrome,
type A and B
For possible self-use, as it is a perfect match, and a donor may not be found.
Umbilical cord blood collected at birth contains HSCs that are, by definition, a perfect genetic match to the baby, since it is the baby’s blood. The cord blood can be processed and the HSCs cryopreserved, or “banked.” The valuable HSCs can be maintained in a viable state for more than 20 years, and possibly much longer.C,N
Private banking of a baby’s cord blood is like having a “biological insurance policy.” Perfectly matched HSCs would be available for use should an appropriate medical need arise as the child grows up. Cord blood is available on-demand and does not require a search for a donor or a surgical procedure to obtain. Nor can it ever be released to anyone else without the parents’ permission.
An estimated 10,000-15,000 people/year who need an HSC transplant cannot find a related bone marrow donor that is a sufficiently close match, from the public data base.M For bone marrow transplants, the probability of finding a match varies with race/ethnicity.L Whites of European descent have the highest probability, at 75%, and blacks of South or Central American descent the lowest, at %. The likelihood of finding a bone marrow match in a donor registry is 46% for whites of Middle Eastern or North African descent, and ranges from 27-52% for Hispanics, Asians, Pacific Islanders, and Native Americans. 6 The probability of finding a match also tends to be lower for mixed-race individuals.
Similarly, for cord blood stored in public banks, the probability of a person finding a match varies with race/ethnicity. The proportion of donors to the New York Blood Center’s National Cord Blood Program, the oldest and largest public cord blood bank in the U.S., is about 37% Caucasian, 21% Hispanic, 20% African American (at least one parent), 13-15% multi-race, and 8% Asian.M
For siblings and other family members.
A sibling and other immediate family member could be at least a partial match for the baby’s HSCs and thus also potentially benefit from cord blood stored in a family bank in the case of future need.
A sibling has a 25% chance of being a full match, a 50% chance of being a partial match, and a 25% chance of not matching at all. The biological parents of a baby will always be a partial match, as the egg and sperm each contribute half of the baby’s DNA.
It may be wise to consider banking cord blood if a disease runs in the family, such as sickle cell anemia, leukemia, or another type of blood disorder. Cord blood HSC’s from an unaffected family member could still be a match for an affected relative thus be available for transplant if the need arises.
However, a child would not be able to use his or her own cord blood to treat a genetic disorder, blood cancers such as leukemia, and possibly some other diseases with an immune or heritable component. This is because the cells in the cord blood would either carry the same affected genes or have already shown a predisposition toward cancer.
The extent of a match — also described as the histocompatibility of a donor tissue, or the likelihood that it will be accepted by the recipient — is determined by the human leukocyte antigen (HLA) system. HLAs are molecules on the surface of cells that help the body’s immune system distinguish its own cells from foreign cells, such as bacteria and other infectious microorganisms or cancer cells. When the body’s immune system sees an HLA protein — also called an antigen — that it does not recognize, it launches an attack to destroy the invading cell or microorganism. This is the basis for the body’s ability to fight infection.
In transplantation, this is the mechanism that can trigger rejection of a donor organ. In a hematopoietic stem cell transplant it can cause Graft-versus-Host Disease (GvHD). In GvHD, it is the immune cells in the donor graft that see the cells of the person they are transplanted into as foreign. This triggers an immune reaction that can cause severe and sometimes chronic symptoms, including organ damage.
GvHD does not occur when people receive their own cells, which is called an autologous transplant.B It can occur only with a transplant of donor cells — an allogeneic transplant — and is less likely to occur the closer the match is between the donor and recipient. When the donor and recipient are related, the risk of GvHD is about 30-40%; whereas in unrelated transplants the chance for GvHD rises to about 60-.B
There are three types or classes of Human Leukocyte Antigens (HLA). Class I and II antigens are the most immunogenic — that is, the most likely to cause rejection of donor tissue, if the donor and recipient do not match. Among these, six HLAs in particular are typically tested to determine if a donor cord blood sample is a suitable match for transplant into a recipient.
If a donor and recipient have identical antigens at all six HLA sites tested (6/6), the cord blood sample is considered to be a perfect match. If the donor and recipient have the same antigens at three specific HLA sites (HLA-DR, HLA-B, and HLA-A) or alternatively, at four or five of the six HLAs tested, the donor tissue will be considered to be a partial match.
A full biological brother or sister of a possible cord blood donor, by definition, shares the same parents as their sibling. All children inherit half of their DNA from one parent and half from the other. Therefore, each sibling has a 25% chance of being a perfect match and a 25% chance of not being a match at all. Each has a 50% chance of matching three, four, or five antigens and being at least a partial match.
A person has two copies of each gene; (except those genes located on the sex, X and Y chromosomes.) A child inherits one copy of each gene from the mother and one copy from the father. The HLA genes are inherited as a group. Thus each parent has a specific cluster or “haplotype”, with six main genes that are inherited together. From the chart below, we can see that two parents each with two different HLA haplotypes, can have children of four different genetic HLA types.
A full biological brother or sister of a possible cord blood donor, by definition, shares the same parents as their sibling. All children inherit one set of HLA genes from one parent and one from the other. Therefore, each sibling has a 25% chance of being a perfect match and a 25% chance of not being a match at all. Each has a 50% chance of being at least a partial match.
What is umbilical cord tissue, how is it collected and why is it important?
Cord tissue surrounds the blood vessels in the umbilical cord. Like cord blood, cord tissue also contains stem cells with potential medical uses.
The stem cells present in cord tissue differ from those in cord blood. Cord tissue contains mesenchymal stem cells (MSCs), which are non-hematopoietic (blood forming) stem cells. In the developing embryo, MSCs are divided and develop into many different types of cells in the body. Almost every organ and tissue in a child’s body developed from MSCs.
The MSCs collected from umbilical cord tissue are a perfect match to the baby, and could be a partial match to siblings and possibly other relatives. Matching of MSCs, is based on the same HLA antigens, which are present in all of the cells in a child’s body, just like the HSCs collected from cord blood.
There is no risk or harm to the mother or baby involved in the collection of cord tissue. After the birth of the baby and delivery of the placenta (and usually after the collection of the cord blood), the obstetrician or midwife can collect the cord tissue. A 3-5 inch section of the cleaned umbilical cord is typically cut out and placed into a sterile collection container. (If not stored, the cord, like the placenta and cord blood, is disposed of.) The container is transported to the laboratory for processing and cryogenic storage, usually in the same package as the cord blood.
Hundreds of clinical trials worldwide are evaluating the potential for MSC-based cell therapy to treat a variety of diseases and for tissue repair and regenerative medicine. O In the laboratory, human MSCs have been shown to be able to mature to form osteocytes (bone cells), chondrocytes (cartilage), adipocytes (fat cells), hepatocytes (liver cells), pancreatic cells (islet cells that produce insulin), and neuronal cells (which make up nerves). O
Research is continuing to determine how best to use MSCs for transplantation, including optimal doses, routes of administration, how and when they are most likely to engraft, and where they go when they are introduced into the circulation. P
Ongoing studies to explore the potential therapeutic uses of MSCs are focusing in particular on their role in stimulating healing and tissue repair and regeneration. For instance, clinical trials are investigating the use of MSCs to repair extensive bone breaks and damaged cartilage, and for treating spinal cord injuries and diseases that affect cardiac or skeletal muscles. The regenerative potential of MSCs is the focus of ongoing clinical studies in patients with type 1 diabetes, rheumatoid arthritis, Parkinson’s disease, and Crohn’s disease, and many others.
Evidence published in the scientific literature suggests that umbilical cord-derived MSCs might have a therapeutic advantage over other sources due to their more primitive, proliferative, and immunosuppressive characteristics, especially for treating autoimmune and neurodegenerative diseases.
MSCs and HSCs — derived from cord tissue and cord blood, respectively — are different kinds of stem cells that have different potential therapeutic uses. One cannot be used in place of the other.
Collecting cord tissue at birth and banking it for future medical use provides an available resource of genetically matched MSCs. Collecting cord blood does the same for HSCs. Thus, banking both cord blood and cord tissue would make both HSCs and MSCs available for future use, increasing both the child’s and the family’s potential treatment options.
Intensive research efforts are underway worldwide to develop new techniques for using MSCs from cord tissue for transplant. Clinical studies are ongoing in a broad and expanding range of diseases and medical conditions for which HSCs from cord blood may be used. The future for the use of both of these types of stem cells is very bright and exciting.
A Brief History of Cord Blood Banking & Transplant
- Dr. Hal Broxmeyer, of Indiana University (Indianapolis, IN), analyzed human cord blood for the presence of hematopoietic stem cells (HSC’s) and progenitor cells. He envisioned using these cells for transplant to reconstitute the human hematopoietic system.
- Dr. A.D. Auerbach, of the Rockefeller University (New York, NY), showed that prenatal diagnosis could be used to rule out Fanconi anemia in the unborn sibling of a child with Fanconi anemia, setting the stage for the first cord blood stem cell transplant.F The fetus would have a 75% chance of not having the disease, and if so, once born the infant’s cord blood could potentially be transplanted to the affected sibling.
- The first related cord blood stem cell transplant was performed in 1988 in Paris, France, in a procedure led by Professor Eliane Gluckman. The patient was a child with Fanconi anemia and the donor was an HLA-identical sibling shown by prenatal testing not to have the disease. (Since the genes for Fanconi anemia and HLA type are on different chromosomes, this is quite possible.) The transplant was successful, without Graft vs Host Disease (GvHD), and the patient was alive and free of disease more than 15 years after the transplant. The donor stem cells fully reconstituted the patient’s hematologic and immune system.S,F
- Transplantation of umbilical cord blood from an HLA-identical sibling to treat a child with chronic myelogenous leukemia (CML) was reported. T The recipient had first been treated with myeloablative therapy to destroy existing HSCs. (Basically, all of the cells in the sick sibling’s bone marrow were intentionally destroyed with .) The donor stem cells successfully engrafted in the recipient’s bone marrow and were documented in the circulating blood. This case showed that umbilical cord blood contains sufficient numbers of HSCs to treat children with leukemia following myeloablative therapy. Unfortunately, in this patient the CML recurred.
- The first HLA-partially matched cord blood transplant (not a complete match of all six tested HLA antigens; see Glossary for definition of HLA system) to treat a child with acute lymphoblastic leukemia (ALL) was reported.
- An umbilical cord blood transplant in an adult with chronic myelogenous leukemia (CML) was reported. U A 26-year-old patient received a cord blood transplant from an unrelated donor after myeloablative therapy. The cord blood was obtained from a public blood bank. The donor-recipient pair were a 5/6 HLA match. The donor’s stem cells successfully engrafted and the recipient’s peripheral blood was completely replaced by donor-derived blood cells. Eight months after the transplant, the patient had no evidence of CML.
- Unrelated umbilical cord blood transplants in children were reported.G Twenty-five children with various malignant and non-malignant diseases received cord blood transplants from unrelated donors. One donor-recipient pair was a perfect (6/6) match, 20 had one mismatch (5/6), three mismatched at two HLA sites (4/6), and one pair mismatched at three sites (3/6). Twelve of the 25 children (48%) survived and did not have a disease-related event for The study demonstrated that partially mismatched (at 1 to 3 HLA sites) cord blood transplants from unrelated donors were a possible, though imperfect, source of stem cells which could sometimes reconstitute the hematopoietic system.
- Report of successful umbilical cord blood stem cell transplant in a child with sickle cell anemia was published. V The patient received cord blood cells collected from a sibling who was an identical HLA match, and was a carrier of the sickle cell trait, but did not have the disease. Complete donor cell engraftment was reported, with no graft-vs-host-disease. The recipient was cured of sickle cell anemia.
- The U.S. Food and Drug Administration (FDA) introduces an Investigational New Drug (IND; see Glossary) for cord blood under the Cord Blood Transplantation Study (COBLT).
- A published study shows less risk of both acute and chronic graft-versus-host disease with umbilical cord blood transplants from HLA-identical siblings compared to bone marrow transplants from HLA-identical siblings, establishing the superiority of cord blood HSCs to peripheral blood HSCs. H
- Fifteen years of basic science and clinical research, and accumulated experience with individual cases of cord blood stem cell transplantation, demonstrates successes and promise of using cord blood to treat a variety of hematologic, immunologic, genetic, and malignant diseases.
- An estimated 30,000 cord blood stem cell transplants have been performed to date, targeting at least 80 different disorders.
- Within the past decade, researchers have begun to examine the effectiveness of using cord blood transplantation to treat a broader range of disorders including, for example, type I diabetes, cerebral palsy, autism, sickle cell disease, Alzheimer’s disease, multiple sclerosis, and metabolic disorders.
- Since the mid-2000s, clinicians have been optimizing approaches that use two of cord blood for adult transplants. Scientists have also been developing methods to multiply the number of stem cells in a single unit of cord blood, prior to transplantation, to allow for expanded dosing and transplants in larger individuals.
Processing & Storage of Cord Blood and Cord Tissue
What happens to a cord blood sample from the time of its collection until it may be needed for a transplant?
The cells in cord blood remain stable for up to about 72 hours after collection at room temperature, during the time they are transported from the site of the birth to the laboratory.
In the laboratory, most of the red blood cells and the liquid portion of the blood, known as the plasma, are usually removed. These components of the blood do not contain hematopoietic stem cells (HSCs) and do not need to be stored.
A cryopreservative is added to the remaining cells, which include the HSCs.
The combined fluid is then cooled in a controlled manner to -196 degrees Centigrade. The sample is transferred to cryo-storage tanks (which are basically big, sophisticated, well monitored thermos bottles) where it is stored in vapor nitrogen or liquid nitrogen.
Before the HSCs are cryopreserved, the lab will perform quality testing to measure the viability (percent alive) of the stem cells and the number of HSCs in the sample. Cultures will be done to look for any bacterial contamination.
A sample of the mother’s blood will also be tested to detect any diseases or infectious agents present at the time of delivery that could have been transferred to the cord blood.
Do different cord blood laboratories process samples differently? If so, is there any evidence that some techniques yield better results than others? Are there gold standards?
Cord blood and tissue processing differs between cord blood processing laboratories.
Maze Cord Blood uses Community Blood Services (CBS) to process the cord blood and cord tissue samples it collects. CBS uses the state-of-the-art, fully automated Sepax S-100 processing system. It is a sterile, single-use, closed system, which ensures that the cord blood does not come in contact with the external environment, thus minimizing the chances of contamination.
Once reduced in volume, the sample is mixed with a 55% DMSO/Dextran 40 cryopreservative solution using the COOLMIX AS-210 automated temperature-controlled system to cool the cells. Each sample is labeled with a unique identifying number. The stem cells are stored in nitrogen tanks using vapor (as opposed to liquid) nitrogen, which maintains a consistent temperature throughout the tank and better protects the samples from any infectious agents, which could theoretically be able to “swim” through liquid nitrogen and potentially spread from one sample to another. Tank temperatures are continuously monitored, with back-up alarm systems in place to warn of even the slightest temperature variability.
Among the differences in sample processing between cord blood banks is the choice of anticoagulant added to the cord blood after collection. An anticoagulant prevents blood clots from forming while the sample is in transit to the lab, which would decrease the number of HSCs left after processing. The most commonly used anticoagulants for processing cord blood are citrate phosphate dextrose (CPD) and lyophilized (dried) heparin.
Maze Cord Blood uses CPD as studies show it to be the safest, most effective anticoagulant available today. Heparin is not the anticoagulant recommended by the FDA or the transplant community, mainly because it tends to break down after about 12 hours. This can allow blood clots to form in the baby’s cord blood sample and make it unsuitable for processing.
But to answer the question, fortunately, or unfortunately, there are no externally validated studies that show that any particular blood bank’s proprietary methods of collection, processing, or storage is best. All of the reputable and approved banks seem to have similar, if not identical, results.
Are there standards and regulatory guidelines that must be met by public and/or private cord blood banks (e.g., FDA, state authorities, AABB, accrediting organizations)? Does having multiple accreditation mean that a bank is better?
Food and Drug Administration (FDA) Regulation and Licensing
All cord blood banks must register with the FDA. In addition, the FDA sets standards for testing and processing cord blood and inspects facilities to ensure that proper practices are being followed. This applies to public and private cord blood banks.
The FDA views cord blood as a biological product and, therefore, its regulation falls under the agency’s Center for Biologics Evaluation and Research (CBER). A cord blood bank or laboratory that performs any of the steps in cord blood collection, processing, and/or storage has to register with the FDA. They are subject to FDA inspections to ensure that they are in compliance with FDA regulations.
As stated by the FDA: “Cord blood stored for personal use and for use in first- or second-degree relatives that also meets other criteria in FDA’s regulations does not require approval before use. Private cord banks must still comply with other FDA requirements, including establishment registration and listing, donor screening and testing for infectious diseases (except when used for the original donor), reporting and labeling requirements, and compliance with current good tissue practice regulations.”A
Cord blood that is stored in public banks and intended for use by patients unrelated to the donor is viewed as a “drug” and a biological product by the FDA. It must be licensed for use in a medical procedure, under a Biologics License Application (BLA) and meet established current Good Manufacturing Practice (GMP) processing requirements. Unlicensed cord blood units are considered to be investigational products and require an Investigational New Drug (IND) application for their use in a transplant procedure.A
In addition to FDA registration and regulations, private cord blood banks in the U.S. may also receive other accreditation. This represents a type of quality assurance, indicating, for example, that a bank follows established procedures and keeps clear and appropriately maintained records.I Accreditation is not a form of regulation and does not endorse or mandate differences in techniques or technologies used to process and store cord blood. In other words, it just confirms that minimum standards are being met.
The two main accrediting agencies are the American Association of Blood Banks (AABB) and the Foundation for the Accreditation of Cellular Therapy (FACT).
AABB is an international organization. As stated on its website, “AABB encourages innovations and improvements in technology and does not endorse any one method or manufacturer over another.”J It publishes voluntary standards for cord blood banking that describe the minimum acceptable requirements for facilities to receive accreditation. AABB assesses a facility that applies for AABB accreditation to ensure compliance with its standards. Re-evaluation takes place every 2 years to renew accreditation.
FACT is a voluntary accreditation based on compliance with the organization’s standards, verified by on-site, peer-reviewed inspections. Clinical programs must perform a specified minimum number of transplants each year, and collection facilities must perform a requisite number of cell collection procedures annually. “Accredited programs utilize processes guided by quality management systems.”
The Value of Accreditation
Having accreditation for banking cord blood and cord tissue stem cells shows that a laboratory meets international standards for processing and storing samples. Accreditation also indicates that a laboratory undergoes regular inspections by the accrediting organization. Whenever a stored cord blood or tissue unit is being considered for transplantation, accreditation of the processing and storage bank will be an important factor in the acceptance of the sample by major transplant centers globally.
For parents, accreditation provides assurance that their baby’s cord blood and cord tissue samples will be properly and safely processed and stored, in compliance with internationally accepted standards.
As stated in a recent review article: “Accreditation establishes a uniform level of practice and promotes high-quality products/practices, leading to improved patient outcomes and elevates the bank’s position as a quality organization and informs patients, health insurance companies, and governments that your organization is dedicated to excellence in patient care and laboratory practices. Accreditation provides evidence of external validation through on-site inspections and facilitates the establishment of quality management and process control to minimize liabilities and regulatory non-compliance.”W
How is cord tissue collected?
The cord tissue is simply a piece of the umbilical cord itself. The cord tissue is collected after the cord blood, as the umbilical cord is needed to carry the cord blood from the placenta in to the collecting bag.
After this, a section of the umbilical cord, usually about six inches, is cleaned, and cut, and placed in the specimen jar provided by the cord blood lab in the collection kit.
How is cord tissue processed?
Some banks store the umbilical cord tissue sample essentially intact, with minimal processing, just cutting the 6-inch or so length of cord into small segments for cryopreservation. Other laboratories first process the tissue to extract the stem cells, prior to cryopreservation.
Is there a difference between storing whole cord tissue compared to processing the tissue before storing it?
Umbilical cord tissue contains three different types of cells: mesenchymal stem cells MSCs), endothelial cells, and epithelial cells. If whole cord is stored, then all three cell types would be present in the cryopreserved sample. Processing of the tissue prior to storage isolates the MSCs and only these are then cryopreserved.
Both strategies will yield MSCs suitable for culture and ultimate transplantation.
Currently, most clinical trials are focusing on the potential use of MSCs, as opposed to endothelial and epithelial cells.
Banking whole tissue is faster and easier. However, if the stem cells are needed in the future, once the whole cord tissue sample is thawed, processing would be required to extract the MSCs and grow them in culture to expand the number of stem cells so there is a sufficient amount for transplantation. This can be a lengthy and costly process. In addition, the more extensive processing involved in culturing the cells would mean that the FDA would view the resulting MSCs as a drug product, requiring an Investigational New Drug (IND) application for therapeutic use.
The main advantage of extracting MSCs from the fresh cord tissue sample is the rapid availability of the stem cells if they should be needed, with less need for additional processing or culturing.
At Maze Cord Blood, we have decided to process the cord tissue, prior to freezing, for the above reasons, despite the fact that it is a more time consuming process.