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.

Definition and collection

Cord blood is a sample of blood taken from a newborn baby's umbilical cord. It is a rich source of hematopoietic stem cells, which are precursors to blood cells. As such, they have been used to treat certain diseases of the blood and immune system. The next largest group is inherited diseases (of red blood cells, the immune system and certain metabolic abnormalities.) Patients with lymphoma, myelodysplasia and severe aplastic anemia have also been successfully transplanted with cord blood. Cord blood is collected from the umbilical cord vein attached to the placenta after the umbilical 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. One unit of cord blood generally lacks stem cells in a quantity sufficient 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, cord clamping should be delayed a minimum of two minutes to prevent anemia over the first three months of life and enriching iron stores and ferritin levels for as long as six 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, and it is not during 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.

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. 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.[4]

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[5]) 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;"[5]

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),[6] in order to establish the inventory of non embryonal stem cell units necessary to provide unrelated, matched grafts for patients.[7][8]

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.[9] Several states also require accreditation, including New York, New Jersey, and California. Any company not accredited within those states are not legally permitted to collect cord blood from those states, even if the company is based out of state. Potential clients can check the New York accreditation status from the New York Umbilical Cord Blood Banks Licensed to Collect in New York. Both public and private cord blood banks are also 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 laboratories from the AABB list of accredited cord blood laboratories or the FACT search engine of accredited cord blood banks (on their home page). Other countries also have regulations pertaining to cord blood. In the United Kingdom, the Human Tissue Authority (www.hta.gov.uk) regulates the cord blood banking.

Today, cord blood banking in Canada is primarily conducted by private cord blood banks, which require payment in order to store a child's cord blood stem cells. Recently, however, the government has launched an initiative that will fund the creation of a national public cord blood bank. The initiative will cost $48 million over the course of the next 8 years, and will provide families all over the country with the chance to donate their child's umbilical cord blood to a national registry. 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.

Research

Though uses of cord blood beyond blood and immunological disorders is speculative, some research has been done in other areas.[10] 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 for Neonatal Hypoxic-Ischemic Encephalopathy[11][12] is being studied in humans, and earlier stage research is being conducted for treatments of stroke,[13][14][15] 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.[10][16][17]

Training programs for clinicians and researchers have been adopted throughout the world, in order to coordinate the research efforts. In 2004 Eurocord,[18] an international platform specialized in clinical research on umbilical cord blood Stem cells., was founded under efforts coordinated by Pr. Gregory Katz and Eliane Gluckman. Eurocord centralizes and analyzes clinical data from 511 transplant centers in 56 countries. Funded by the European Union, Eurocord works closely with the European School of Haematology.[19] In 2007, the association was recognized by the Medicen[20] network of cell therapy clusters. Eurocord also develops training programs for clinicians and researchers specialized in blood cancer and cell therapy. In 2010, Eurocord became part of the French Agence de la biomédecine.[21]

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. [22] Mesenchymal stem cells differentiate to build bone, cartilage and connective tissue, and they can also mediate the body’s inflammatory response to damaged or injured cells. [23] [24] [25] [26] There have been no clinical trials in humans yet that have used MSCs derived from cord tissue, though some have looked into the possibility of its use in treating certain diseases in animals. [27] [28] [29] [30] [31]

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.

Controversy

The policy of the American Academy of Pediatrics states that "private storage of cord blood as 'biological insurance' is unwise" unless there is a family member with a current or potential need to undergo a stem cell transplantation.[32][33][34] The American Academy of Pediatrics also notes that the odds of using one's own cord blood is 1 in 200,000 while the Institute of Medicine says that only 14 such procedures have ever been performed.[35] Private storage of one's own cord blood is unlawful in Italy and France, and it is also discouraged in some other European countries. The American Medical Association states "Private banking should be considered in the unusual circumstance when there exists a family predisposition to a condition in which umbilical cord stem cells are therapeutically indicated. However, because of its cost, limited likelihood of use, and inaccessibility to others, private banking should not be recommended to low-risk families."[36] The American Society for Blood and Marrow Transplantation and the American Congress of Obstetricians and Gynecologists also encourage public cord banking and discourage private cord blood banking. Nearly all cord blood transfusions come from public banks, rather than private banks,[34][37] partly because most treatable conditions can't use one's own cord blood.[38][39]

Cord blood contains hematopoietic stem cells (which can differentiate only into blood cells), and should not be confused with embryonic stem cells (pluripotent stem cells), which can differentiate into any cell in the body.[32][37] Cord blood stem cells are blood cell progenitors which can form red blood cells, white blood cells, and platelets. This is why cord blood cells are currently used to treat blood and immune system related genetic diseases, cancers, and blood disorders. On the possibility that cord blood stem cells could be used for other purposes, the World Marrow Donor Association and European Group on Ethics in Science and New Technologies states "The possibility of using one’s own cord blood stem cells for regenerative medicine is currently purely hypothetical....It is therefore highly hypothetical that cord blood cells kept for autologous use will be of any value in the future" and "the 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."[40]

The American Academy of Pediatrics supports efforts to provide information about the potential benefits and limitations of cord blood banking and transplantation, 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".[41] 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.

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.[42] The National Marrow Donor Program forecasts that by the year 2015, there will be 10,000 cord blood transplants worldwide per year using publicly banked cord blood. It is therefore beneficial to build public repositories of cord blood donations. 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.[43]

In March 2004, the European Union Group on Ethics (EGE) has issued Opinion No.19[44] 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."[44]

In May 2006 The World Marrow Donor Association (WMDA) Policy Statement for the Utility of Autologous or Family Cord Blood Unit Storage[45] 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.

As of spring 2008, there were several known instances where autologous use of cord blood was possible, though other areas of research are more speculative.[46][47] [48][49]

See also

References

  1. ↑ Cord Blood Banking: Donating Umbilical Cord Blood, Buzzle.com
  2. ↑ 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. ↑ Christopher D. Hillyer, Ronald G. Strauss & Naomi L. C. Luban. (2004). Handbook of Pediatric Transfusion Medicine. Academic Press. pp. 295, 296. ISBN 0-12-348776-5.
  5. 1 2 2007 "Policy Statement on Cord Blood Banking" Check |url= value (help). The American Academy of Pediatrics.
  6. ↑ NIH data
  7. ↑ 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.
  8. ↑ Raymer, Elizabeth (2005-10-14). "New strategy will boost cord blood stem cells". University of Toronto. Archived from the original on September 19, 2006. Retrieved September 20, 2006. External link in |work= (help)
  9. ↑ http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=1271
  10. 1 2 Hal E. Broxmeyer PhD and Franklin O. Smith MD (2009). "Cord Blood Hematopoietic Cell Transplantation.". Thomas' Hematopoietic Cell Transplantation, Fourth Edition (Fourth Edition).
  11. ↑ Haller M J; Viener, HL; Wasserfall, C; Brusko, T; Atkinson, MA; Schatz, DA; 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.
  12. ↑ http://clinicaltrials.gov/ct2/show/NCT00593242?term=NCT00593242&rank=1
  13. ↑ Vendrame M; Gemma, Carmelina; Pennypacker, Keith R.; Bickford, Paula C.; Davis Sanberg, Cyndy; Sanberg, Paul R.; Willing, Alison E.; 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.
  14. ↑ Vendrame M; Gemma, Carmelina; Mesquita, Dirson De; Collier, Lisa; Bickford, Paula C.; Sanberg, Cyndy Davis; Sanberg, Paul R.; Pennypacker, Keith R.; Willing, Alison E.; 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.
  15. ↑ Revoltella RP; Papini, Sandra; Rosellini, Alfredo; Michelini, Monica; Franceschini, Valeria; Ciorba, Andrea; Bertolaso, Lucia; Magosso, Sara; Hatzopoulos, Stavros; Lorito, Guiscardo; Giordano, Pietro; Simoni, Edi; Ognio, Emanuela; Cilli, Michele; Saccardi, Riccardo; Urbani, Serena; Jeffery, Rosemary; Poulsom, Richard; Martini, Alessandro; 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.
  16. ↑ Harris DT; Badowski, Michael; Ahmad, Nafees; Gaballa, Mohamed A; 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.
  17. ↑ Haller MJ; Viener, Hilla-Lee; Wasserfall, Clive; Brusko, Todd; Atkinson, Mark A.; Schatz, Desmond A.; 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.
  18. ↑ http://www.eurocord-ed.org/
  19. ↑ http://www.esh.org/
  20. ↑ http://www.medicen.org/
  21. ↑ http://www.agence-biomedecine.fr/article/528
  22. ↑ Dominici M; Le Blanc, K; Mueller, I; Slaper-Cortenbach, I; Marini, FC; Krause, DS; Deans, RJ; Keating, A; Prockop, DJ; Horwitz, EM; et al. (2006). "Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement". Cytotherapy. 8 (4): 315–317. doi:10.1080/14653240600855905. PMID 16923606.
  23. ↑ Uccelli A; Moretta, L; Pistoia, V; et al. (2008). "Mesenchymal stem cells in health and disease.". Nature Reviews Immunology 8 (9): 726–735. doi:10.1038/nri2395. PMID 19172693.
  24. ↑ Schugar, R.C.; Chirieleison, SM; Wescoe, KE; Schmidt, BT; Askew, Y; Nance, JJ; Evron, JM; Peault, B; Deasy, BM (2009). "Autologous umbilical cord blood infusion for type 1 diabetes". Journal of Biomedicine and Biotechnology 2009: 1–11. doi:10.1155/2009/789526. PMC 2796378. PMID 20037738.
  25. ↑ Sun, J; Allison, J; McLaughlin, C; Sledge, L; Waters-Pick, B; Wease, 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.
  26. ↑ Giordano A; Galderisi, U; Marino, IR; et al. (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. doi:10.1002/jcp.20959. PMID 17226788.
  27. ↑ Maurya DK; Doi, Chiyo; Kawabata, Atsushi; Pyle, Marla M; King, Clay; Wu, Zhihong; Troyer, Deryl; Tamura, Masaaki; et al. (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. PMC 2988749. PMID 21029413.
  28. ↑ Fu, YS,; Cheng, YC; Lin, MY; Cheng, H; Chu, PM; Chou, SC; Shih, YH; Ko, MH; Sung, MS (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. doi:10.1634/stemcells.2005-0053. PMID 16099997.
  29. ↑ Liu, Y; et al. (2010). "Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis". Arthritis Research & Therapy 12 (6): R210. doi:10.1186/ar3187. PMC 3046518. PMID 21080925.
  30. ↑ Limin Wang; Tran, I; Seshareddy, K; Weiss, ML; Detamore, MS; et al. (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. PMID 19260778.
  31. ↑ Rita Anzalone; Lo Iacono, Melania; Loria, Tiziana; Di Stefano, Antonino; Giannuzzi, Pantaleo; Farina, Felicia; La Rocca, Giampiero; et al. (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.
  32. 1 2 http://pediatrics.aappublications.org/content/119/1/165.full
  33. ↑ "AAP News Release - AAP: CORD BLOOD BANKING FOR FUTURE TRANSPLANTATION NOT RECOMMENDED". www.nationalcordbloodprogram.org. Retrieved 2015-04-17.
  34. 1 2 Thornley, Ian; Eapen, Mary; Sung, Lillian; Lee, Stephanie J.; Davies, Stella M.; Joffe, Steven (03/01/2009). "Private Cord Blood Banking: Experiences and Views of Pediatric Hematopoietic Cell Transplantation Physicians". Pediatrics 123 (3): 1011–1017. doi:10.1542/peds.2008-0436. ISSN 0031-4005. PMID 19255033. Retrieved 2015-04-17. Check date values in: |date= (help)
  35. ↑ "Umbilical cord blood banking: Pros & cons, costs, banking basics". www.webmd.com. Retrieved 2015-04-17.
  36. ↑ "Opinion 2.165 - Umbilical Cord Blood Banking". www.ama-assn.org. Retrieved 2015-04-17.
  37. 1 2 Besser, Dr Richard; Schwartz, Susan; Romo, Christine (2010-05-07). "Cord Blood: Marketing Before Medicine?". ABC News. Retrieved 2015-04-17.
  38. ↑ Allergy/Immunology, Section on Hematology/Oncology and Section on (2007-01-01). "Cord Blood Banking for Potential Future Transplantation". Pediatrics 119 (1): 165–170. doi:10.1542/peds.2006-2901. ISSN 0031-4005. PMID 17200285. Retrieved 2015-04-17.
  39. ↑ Searcey, Dionne; Stewart, Christopher S. (2014-04-25T16:55:00.000Z). "Inside the Private Umbilical Cord Blood Banking Business". Wall Street Journal. ISSN 0099-9660. Retrieved 2015-04-17. Check date values in: |date= (help)
  40. ↑ "http://bloodcell.transplant.hrsa.gov/cord/files/wmdapolicystatement.pdf" (PDF). bloodcell.transplant.hrsa.gov. Retrieved 2015-04-17. External link in |title= (help)
  41. ↑ "Establishing a National Cord Blood Stem Cell Bank Program - Institute of Medicine". www.iom.edu. Retrieved 2015-04-17.
  42. ↑ 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.
  43. ↑ Health Resources and Services Administration
  44. 1 2 Opinion N° 19, European Union Group on Ethics
  45. ↑ 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 (PDF) on September 26, 2006. Retrieved June 2, 2006. External link in |work= (help)
  46. ↑ 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
  47. ↑ 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.
  48. ↑ 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.
  49. ↑ Duke University, Neonatal Hypoxic-Ischemic Encephalopathy; Phase I clinical trial NCT00593242,


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