Cord blood

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.

Collection

Cord blood is obtained by syringing out the placenta through the umbilical cord at the time of childbirth, after the cord has been detached from the newborn.^[1] Cord blood is collected because it contains stem cells, including hematopoietic cells, which can be used to treat hematopoietic and genetic disorders. Although the cord blood does contain stem cells, there are generally not enough stem cells in one unit of cord blood to treat an adult patient. The placenta is a much better source of stem cells since it contains up to ten times more than cord blood.^[2] Some placental blood may be returned to the neonatal circulation if the umbilical cord is not prematurely clamped.^[3] According to Eileen K. Hutton, PhD and Eman S. Hassan, MBBch, there should be a delay of a minimum of two minutes before cord clamping. This prevents anemia over the first 3 months of life and enriching iron stores and ferritin levels for as long as 6 months. (Ref. "Late vs Early Clamping of the Umbilical Cord in Full-term Neonates," JAMA, March 21, 2007) If the umbilical cord is not clamped, such as in an extended-delayed cord clamping protocol, a physiological postnatal occlusion occurs upon interaction with cold air, when the internal gelatinous substance, called Wharton's jelly, swells around the umbilical artery and veins.

Regulation

In the United States, the Food and Drug Administration regulates cord blood under the category of “Human Cells, Tissues, and Cellular and Tissue Based-Products.” The Code of Federal Regulations under which the FDA regulates public and private cord blood banks is Title 21 Section 1271. Both public and private cord blood banks are eligible for voluntary accreditation with either the American Association of Blood Banks AABB or the Foundation for the Accreditation of Cellular Therapy FACT. Potential clients can check the current accreditation status of banks from the AABB list of accredited cord blood banks or the FACT search engine of accredited cord blood banks (on their home page). Other countries also have regulations pertaining to cord blood. It is also found out that no problems arise concerning cord blood donation. ^[4]

Use and applications

Physicians and researchers have begun to make progress evaluating the safety and efficacy of umbilical cord blood stem cells for certain therapeutic uses beyond blood cancers and genetic diseases of the blood.^[5]

The use of cord blood stem cells in treating conditions such as brain injury^[6] and type 1 diabetes^[7] is already being studied in humans, and earlier stage research is being conducted for treatments of stroke,^[8][9] and hearing loss.^[10] However, apart from blood disorders, the use of cord blood for other diseases is not a routine clinical modality and remains a major challenge for the stem cell community.^[5]

Current estimates indicate that approximately 1 in 3 Americans could benefit from regenerative medicine,^[11] and children whose cord blood stem cells are available for their own potential use could be among the first to benefit from new therapies as they become available^{[citation needed]}. With autologous (the person’s own) cells, there is no risk of the immune system rejecting the cells, so physicians and researchers are only performing these potential cord blood therapies on children who have their own stem cells available^{[citation needed]}.

Researchers are exploring the use of cord blood stem cells in the following regenerative medicine applications:

Type 1 Diabetes

A clinical trial underway at the University of Florida (NCT00305344) is examining whether an infusion of autologous cord blood stem cells into children with newly diagnosed Type 1 diabetes will impact metabolic control over time, as compared to standard insulin treatments. Preliminary results demonstrate that an infusion of cord blood stem cells is safe and may provide some slowing of the loss of insulin production in children with Type 1 diabetes.^[12]

Cardiovascular repair

The stem cells found in a newborn’s umbilical cord blood are holding great promise in cardiovascular repair. Researchers are noting several positive observations in pre-clinical animal studies. Thus far, in animal models of myocardial infarction, cord blood stem cells have shown the ability to selectively migrate to injured cardiac tissue, improve vascular function and blood flow at the site of injury, and improve overall heart function.^[11]

Cord blood harvesting

Umbilical cord blood is the blood left over in the placenta and in the umbilical cord after the birth of the baby. The cord blood is composed of all the elements found in whole blood. It contains red blood cells, white blood cells, plasma, platelets and is also rich in hematopoietic stem cells. These stem cells in cord blood have immense potential to cure heart related disease, eighty diseases in blood, infection such as Aspergillosis ^[13] and genetic disorders.^[2]

There are several methods for collecting cord blood. The method most commonly used in clinical practice is the “closed technique”, which is similar to standard blood collection techniques. With this method, the technician cannulates the vein of the severed umbilical cord using a needle that is connected to a blood bag, and cord blood flows through the needle into the bag. On average, the closed technique enables collection of about 75 ml of cord blood.^[14]

Collected cord blood is cryopreserved and then stored in a cord blood bank for future transplantation. A cord blood bank may be private (i.e. the blood is stored for and the costs paid by donor families) or public (i.e. stored and made available for use by unrelated donors). While public cord blood banking is widely supported, private cord banking is controversial in both the medical and parenting community. Although umbilical cord blood is well-recognized to be useful for treating hematopoietic and genetic disorders, some controversy surrounds the collection and storage of umbilical cord blood by private banks for the baby's use. Only a small percentage of babies (estimated at between 1 in 1,000 to 1 in 200,000^[15]) ever use the umbilical cord blood that is stored. The American Academy of Pediatrics 2007 Policy Statement on Cord Blood Banking states that:

"Physicians should be aware of the unsubstantiated claims of private cord blood banks made to future parents that promise to insure infants or family members against serious illnesses in the future by use of the stem cells contained in cord blood;"^[15]

Cord blood is stored by both public and private cord blood banks. Public cord blood banks store cord blood for the benefit of the general public, and most U.S. banks coordinate matching cord blood to patients through the National Marrow Donor Program (NMDP). Private cord blood banks are usually for-profit organizations that store cord blood for the exclusive use of the donor or donor's relatives.

Public cord blood banking is supported by the medical community. However, private cord blood banking is generally not recommended unless there is a family history of specific genetic diseases.

New parents have the option of storing their newborn's cord blood at a private cord blood bank or donating it to a public cord blood bank. The cost of private cord blood banking is approximately $2000 for collection and approximately $125 per year for storage, as of 2007. Donation to a public cord blood bank is not possible everywhere, but availability is increasing. Several local cord blood banks across the United States are now accepting donations from within their own states. The cord blood bank will not charge the donor for the donation; the OB/GYN may still charge a collection fee, although many OB/GYNs choose to donate their time.

After the first sibling-donor cord blood transplant was performed in 1988, the National Institute of Health (NIH) awarded a grant to Dr. Pablo Rubinstein to develop the world's first cord blood program at the New York Blood Center (NYBC),^[16] in order to establish the inventory of non embryonal stem cell units necessary to provide unrelated, matched grafts for patients.

In 2005, University of Toronto researcher Peter Zandstra developed a method to increase the yield of cord blood stem cells to enable their use in treating adults as well as children.^[17]

Banking Umbilical Cord Tissue

Expectant parents can now also collect and preserve stem cells from the tissue of the umbilical cord, whose medical name is Wharton’s Jelly. Whereas cord blood is a rich source of Hematopoietic stem cells (HSC) that differentiate to form the lineage of blood cells, cord tissue is a rich source of Mesenchymal stem cells (MSC). The International Society of Cellular Therapy. ISCT, has established criteria for defining MSC. ^[18] Mesenchymal stem cells differentiate to build bone, cartilage and connective tissue, and they are also very effective at mediating the body’s inflammatory response to damaged or injured cells. ^[19] Harvesting the tissue of the umbilical cord can yield between 21 and 500 million MSC. ^[20] By comparison, a typical cord blood collection in a private bank has a median total nucleated cell count of 470 million. ^[21] For parents, private storage at birth of stem cells from both cord blood and cord tissue offer more options for future medical use.

Numerous clinical trials are using MSC derived from the bone marrow of adult volunteers to treat heart disease, stroke, bone disease and injury, and autoimmune diseases such as Type 1 Diabetes, Multiple Sclerosis, and Crohn’s Disease. ^[22] As yet, there are no clinical trials in humans using MSCs derived from cord tissue. However, over 50 studies have used MSC derived from cord tissue to treat animal models of human diseases, including: Lung Cancer, ^[23] Parkinson's Disease, ^[24] Rheumatoid Arthritis, ^[25] Sports injuries to cartilage, ^[26] and Type 1 Diabetes. ^[27]

Currently there is no standard procedure or accrediting criteria for storage of MSC from umbilical cord tissue. Many cord blood banks are storing the cord tissue by freezing an intact segment of the umbilical cord. This procedure has the advantage of waiting for the technology of cell separation to mature, but has the disadvantage that there is no guarantee it will be possible to efficiently retrieve viable stem cells from a previously frozen cord. A few cord blood banks are extracting stem cells from the cord tissue before cryogenic storage. This procedure has the disadvantage that it uses the current separation method, but the advantage that it yields minimally manipulated cells that are treatment ready and comply with FDA regulations on cell therapy products.

The UK NHS Cord Blood Bank

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.

• The first unrelated transplant (the patient was not related to the donor) occurred in February 1998
• Cord blood collected for the NHS Cord Blood Bank is collected by specially trained and dedicated staff. It is collected from the following hospitals – Barnet General, Northwick Park, Watford, Luton and Dunstable and St George’s in Tooting
• Trained NHS Cord Blood Bank staff contact mothers who have registered to donate before they have their baby to ask some simple lifestyle questions and to obtain verbal consent for the collection, testing and use of the donation
• The NHS Cord Blood Bank has issued cord blood units to 22 countries. This is a reciprocal arrangement internationally enabling patients worldwide to get the best treatment
• The NHS Cord Blood Bank is accredited by NetCord-FACT and licensed by the Human Tissue Authority

Medical Guidelines & Legislation

While the American Academy of Pediatrics discourages private banking except in the case of existing medical need, it also believes that information about the potential benefits and limitations of cord blood banking and transplantation should be provided so that parents can make an informed decision. In addition, the American College of Obstetricians and Gynecologists recommends that if a patient requests information on umbilical cord blood banking, balanced information should be given.

Cord blood education is also supported by legislators at the federal and state levels. In 2005, the National Academy of Sciences published an Institute of Medicine (IoM) report titled, "Establishing a National Cord Blood Stem Cell Bank Program". The IoM report recommended that expectant parents be given a balanced perspective on their options for cord blood banking. In response to their constituents, state legislators across the country are introducing legislation intended to help inform physicians and expectant parents on the options for donating, discarding or banking newborn stem cells. Currently 17 states, covering two-thirds of U.S. births, have enacted legislation recommended by the IoM guidelines.

Controversy

While there is general support in the medical community for public banking of cord blood, the question of private banking has raised objections from many governments and nonprofit organizations. The controversy centers on varying assessments of the current and future likelihood of successful uses of the stored blood. In March 2008, a paper was published by Nietfeld et al.^[28] in the journal Biology of Blood and Marrow Transplantation which computed the lifetime probability (up to age 70) that an individual in the US would undergo a stem cell transplant. The likelihood of an autologous transplant using your own stem cells is 1 in 435, the likelihood of an allogeneic transplant from a matched donor (such as a sibling) is 1 in 400, and the net likelihood of any type of stem cell transplant is 1 in 217.^{[citation needed]}

The National Marrow Donor Program estimates that by the year 2015, there will be 10,000 cord blood transplants worldwide per year using publicly banked cord blood. It is therefore vitally important to build public repositories of cord blood donations throughout the world. In the United States, the Health Resources and Services Administration (HRSA) of the US Dept. of Health and Human Services is responsible for funding national programs to register marrow donors and bank cord blood donations.^[29]

In March 2004, the European Union Group on Ethics (EGE) has issued Opinion No.19^[30] titled Ethical Aspects of Umbilical Cord Blood Banking. The EGE concluded that "[t]he legitimacy of commercial cord blood banks for autologous use should be questioned as they sell a service, which has presently, no real use regarding therapeutic options. Thus they promise more than they can deliver. The activities of such banks raise serious ethical criticisms."^[30] However, in the final section 1.27 of their Opinion, the EGE admits that: "if in the future regenerative medicine developed in such a way that using autologous stem cells became possible, then the fact to have one's own cord blood being stored at birth could increase the chance of having access to new therapies."^[30]

In May 2006 The World Marrow Donor Association (WMDA) Policy Statement for the Utility of Autologous or Family Cord Blood Unit Storage^[31] stated that:

1. The use of autologous cord blood cells for the treatment of childhood leukemia is contra-indicated because pre-leukemic cells are present at birth. Autologous cord blood carries the same genetic defects as the donor and should not be used to treat genetic diseases.
2. There is at present no known protocol where autologous cord blood stem cells are used in therapy.
3. If autologous stem cell therapies should become reality in the future, these protocols will probably rely on easily accessible stem cells.

Emerging Stem Cell Applications

Brain Injury Cerebral Palsy Type 1 Diabetes Heart Disease

As of spring 2008, there are several known instances where autologous use of cord blood is indicated:

1. Whereas the WMDA cautioned against autologous transplant for diseases with a genetic signature, there are pediatric cancers (ex: neuroblastoma) and acquired conditions (ex: aplastic anemia) which can be treated by autologous transplant. There has even been one autologous transplant for leukemia^[32]
2. Type 1 diabetes, also known as juvenile diabetes, has been shown to improve if treated shortly after onset with an infusion of autologous cord blood.^[33] The American Diabetes Association reports that 1 in 7000 children is diagnosed each year with Type 1 diabetes, and 1 in 600 children are living with it.
3. A Phase I clinical trial is underway at Duke University to investigate whether cerebral palsy and other forms of pediatric brain injury may respond to infusions of autologous cord blood.^[34] The Brain Injury Association of America^[35] estimates that the prevalence of Cerebral Palsy is about 1 in 300 among children up to age 10.

See also

• Bone Marrow Donors Worldwide
• Cord blood bank
• Stem cell
• Doula
• Umbilical cord
• Placenta cord banking
• Gift of Life Bone Marrow Foundation
• Relicord
• Americord Registry
• LifeLine Cryogenics

References

1. ^ Cord Blood Banking: Donating Umbilical Cord Blood, Buzzle.com
2. ^ ^{a b} Cairo MS, Wagner JE (1997). "Placental and/or umbilical cord blood: an alternative source of hematopoietic stem cells for transplantation.". Blood 90 (12): 4665–4678. PMID 9389681. 
3. ^ Umbilical Cord Issues/Delayed Cord Clamping, gentlebirth.org
4. ^ "Cord Blood Donation Problems". http://bloodbanker.com/cord/cord-blood-donation-problems. Retrieved May 28, 2006. 
5. ^ ^{a b} Hal E. Broxmeyer PhD and Franklin O. Smith MD (2009). "Cord Blood Hematopoietic Cell Transplantation.". Thomas' Hematopoietic Cell Transplantation, Fourth Edition (Fourth Edition). http://www3.interscience.wiley.com/cgi-bin/summary/122239838/SUMMARY. 
6. ^ Cord Blood for Neonatal Hypoxic-Ischemic Encephalopathy, Autologous Cord Blood Cells for Hypoxic Ischemic Encephalopathy Study 1. Phase I Study of Feasibility and Safety
7. ^ Haller MJ, etal.; Viener, HL; Wasserfall, C; Brusko, T; Atkinson, MA; Schatz, DA (2008). "Autologous umbilical cord blood infusion for type 1 diabetes.". Exp. Hematol. 36 (6): 710–715. doi:10.1016/j.exphem.2008.01.009. PMC 2444031. PMID 18358588. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2444031. 
8. ^ Vendrame M, et al. (2006). "Cord blood rescues stroke-induced changes in splenocyte phenotype and function.". Exp. Neurol. 199 (1): 191–200. doi:10.1016/j.expneurol.2006.03.017. PMID 16713598. 
9. ^ Vendrame M, et al. (2005). "Anti-inflammatory effects of human cord blood cells in a rat model of stroke.". Stem Cells Dev. 14 (5): 595–604. doi:10.1089/scd.2005.14.595. PMID 16305344. 
10. ^ Revoltella RP, et al. (2008). "Cochlear repair by transplantation of human cord blood CD133+ cells to nod-scid mice made deaf with kanamycin and noise.". Cell Transplant. 17 (6): 665–678. doi:10.3727/096368908786092685. PMID 18819255. 
11. ^ ^{a b} Harris DT, et al. (2007). "The potential of cord blood stem cells for use in regenerative medicine.". Expert Opin. Biol. Ther. 7 (9): 1311–1322. doi:10.1517/14712598.7.9.1311. PMID 17727322. 
12. ^ Haller MJ, et al. (2008). "Autologous umbilical cord blood infusion for type 1 diabetes.". Exp. Hematol. 36 (6): 710–715. doi:10.1016/j.exphem.2008.01.009. PMC 2444031. PMID 18358588. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2444031. 
13. ^ "Bouncing Back!". http://bloodbanker.com/cord/bouncing-back. Retrieved August 16, 2011. 
14. ^ Christopher D. Hillyer, Ronald G. Strauss & Naomi L. C. Luban. (2004). Handbook of Pediatric Transfusion Medicine. Academic Press. pp. 295, 296. ISBN 012-348-776-5. 
15. ^ ^{a b} 2007 "Policy Statement on Cord Blood Banking". The American Academy of Pediatrics. http://aappolicy.aappublications.org/cgi/content/full/pediatrics;119/1/165 2007. 
16. ^ NIH data
17. ^ Raymer, Elizabeth (2005-10-14). "New strategy will boost cord blood stem cells". University of Toronto. Archived from the original on September 19, 2006. http://web.archive.org/web/20060919013034/http://www.news.utoronto.ca/bin6/051014-1723.asp. Retrieved September 20, 2006. 
18. ^ Dominici M, etal.; Le Blanc, K; Mueller, I; Slaper-Cortenbach, I; Marini, FC; Krause, DS; Deans, RJ; Keating, A et al. (2006). "Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.". Cytotherapy. 8: 315–317. PMID 16923606. 
19. ^ Uccelli A, etal.; Moretta, L; Pistoia, V (2008). "Mesenchymal stem cells in health and disease.". Nature Reviews Immunology. 8 (9): 726–735. doi:10.1038/nri2395. PMID 19172693. 
20. ^ Schugar, Rebecca C., etal.; Chirieleison, SM; Wescoe, KE; Schmidt, BT; Askew, Y; Nance, JJ; Evron, JM; Peault, B et al. (2009). "Autologous umbilical cord blood infusion for type 1 diabetes.". Journal of Biomedicine and Biotechnology 2009. doi:10.1155/2009/789526. PMID 20037738. 
21. ^ Sun, Jessica J, etal.; Allison, C; McLaughlin, L; Sledge, B; Waters-Pick, S; Kurtzberg, J (2010). "Differences in quality between privately and publicly banked umbilical cord blood units: a pilot study of autologous cord blood infusion in children with acquired neurological disorders.". Transfusion. 50 (9): 1980–1987. doi:10.1111/j.1537-2995.2010.02720.x. PMID 20546200. 
22. ^ Giordano A, etal.; Galderisi, U; Marino, IR (2007). "From the laboratory bench to the patient’s bedside: An update on clinical trials with mesenchymal stem cells.". Exp. Hematol. 211 (1): 27–35. PMID 17226788. 
23. ^ Maurya DK, etal. (2010). "Therapy with un-engineered naïve rat umbilical cord matrix stem cells markedly inhibits growth of murine lung adenocarcinoma.". BMC Cancer. 10: 590. doi:10.1186/1471-2407-10-590. PMID 21029413. 
24. ^ Fu, YS,; Cheng, YC; Lin, MY; Cheng, H; Chu, PM; Chou, SC; Shih, YH; Ko, MH et al. (2006). "Conversion of human umbilical cord mesenchymal stem cells in Wharton's jelly to dopaminergic neurons in vitro: potential therapeutic application for Parkinsonism.". Stem Cells. 24 (1): 115–124. PMID 16099997. 
25. ^ Liu, Y, etal. (2010). "Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis.". Arthritis Research & Therapy 12: R210. doi:10.1186/ar3187. PMID 21080925. 
26. ^ Limin Wang, etal.; Tran, I; Seshareddy, K; Weiss, ML; Detamore, MS (2009). "A Comparison of Human Bone Marrow–Derived Mesenchymal Stem Cells and Human Umbilical Cord–Derived Mesenchymal Stromal Cells for Cartilage Tissue Engineering". Tissue Engineering Part A. 15 (8): 2259–2266. doi:10.1089/ten.tea.2008.0393. 
27. ^ Rita Anzalone, etal. (2008). "Wharton’s Jelly Mesenchymal Stem Cells as Candidates for Beta Cells Regeneration: Extending the Differentiative and Immunomodulatory Benefits of Adult Mesenchymal Stem Cells for the Treatment of Type 1 Diabetes.". Stem Cell Reviews and Reports. 7 (23): 342–363. doi:10.1007/s12015-010-9196-4. PMID 20972649. 
28. ^ Nietfield, J; Pasquini, MC; Logan, BR; Verter, F; Horowitz, MM (2008). "Lifetime probabilities of hematopoietic stem cell transplantation in the U.S.". Biology of Blood and Marrow Transplantation 14 (3): 316–322. doi:10.1016/j.bbmt.2007.12.493. PMC 2531159. PMID 18275898. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2531159. 
29. ^ Health Resources and Services Administration
30. ^ ^{a b c} Opinion N° 19, European Union Group on Ethics
31. ^ World Marrow Donor Association (2006). "Policy Statement for the Utility of Autologous or Family Cord Blood Unit Storage" (PDF). World Marrow Donor Association. Archived from the original on September 26, 2006. http://web.archive.org/web/20060926115915/http://www.worldmarrow.org/fileadmin/WorkingGroups_Subcommittees/DRWG/Cord_Blood_Registries/WMDA_Policy_Statement_Final_02062006.pdf. Retrieved June 2, 2006. 
32. ^ Hayani, A; Lampeter, E.; Viswanatha, D.; Morgan, D.; Salvi, S. N. (2007). "First report of autologous cord blood transplantation in the treatment of a child with leukemia". Pediatrics 119 (1): 296–300. doi:10.1542/peds.2006-1009. PMID 17200253. 
33. ^ Haller, M.J.; Viener, HL; Wasserfall, C; Brusko, T; Atkinson, MA; Schatz, DA (2008). "Autologous umbilical cord blood infusion for type 1 diabetes". Exp. Hematol 36 (6): 710–715. doi:10.1016/j.exphem.2008.01.009. PMC 2444031. PMID 18358588. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2444031. 
34. ^ Duke University, Neonatal Hypoxic-Ischemic Encephalopathy; Phase I clinical trial NCT00593242, [1]
35. ^ Brain Injury Association of America

LifeLine Cryogenics Cord Blood Bank</big>

External links

General information

• National Marrow Donor Program
• Save the Cord Foundation, a non-profit educational foundation established to create unbiased awareness about the life saving benefits of cord blood.
• Cord Blood Association of Canada — A non-profit organization about cord blood banking.
• The New Jersey Cord Blood Bank (NJCBB)
• The March of Dimes - Umbilical Cord Blood
• Parent's Guide to Cord Blood Foundation, a non-profit educational foundation
• Gift of Life Cord Blood Program
• Cord blood donation
• Cord Blood Science

Free, public donation information

• Alberta Cord Blood Bank — Accepts free collections throughout Canada
• NHS Cord Blood Bank — Accepts free collections throughout England and Wales
• National Marrow Donor Program — Details on umbilical cord blood donation
• ITxM Cord Blood Services — ITxM accepts public cord blood donations in the Chicago area and western Pennsylvania.

Diseases treated with cord blood

• Diseases treatable with hematopoietic cells — i.e., marrow, cord blood and peripheral blood stem cells
• National Cord Blood Program — Frequency of patients transplanted with cord blood by disease