Cord blood

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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 such as cancer.

Contents

Constituents

Cord blood is composed of all the elements found in whole blood – red blood cells, white blood cells, plasma, platelets. [6] Compared to whole blood some differences in the blood composition exist, for example, cord blood contains higher numbers of natural killer cells, lower absolute number of T-cells and a higher proportion of immature T-cells. [7] However, the interest in cord blood is mostly driven by the observation that cord blood also contains various types of stem and progenitor cells, mostly hematopoietic stem cells. [6] [7] [8] Some non-hematopoietic stem cell types are also present in cord blood, for example, mesenchymal stem cells, however these are present in much lower numbers than what can be found in adult bone marrow. [7] [8] Endothelial progenitor cells and multipotent unrestricted adult stem cells can also be found in cord blood. [8] Unlike embryonic stem cells which are pluripotent, cord blood stem cells are multipotent. [8] [9] [10]

Medical uses

Cord blood is used the same way that hematopoietic stem cell transplantation is used to reconstitute bone marrow following radiation treatment for various blood cancers, and for various forms of anemia. [11] [12] Its efficacy is similar as well. [11]

Adverse effects in transplantation

Adverse effects are similar to hematopoietic stem cell transplantation, namely graft-versus-host disease if the cord blood is from a genetically different person, and the risk of severe infection while the immune system is reconstituted. [11] To assure that the smallest amount of complications occur during transplantation, levels of engraftment must be present; specifically both neutrophils and platelets must be being produced. [13] This process of neutrophil and platelet production after the transplant, however, takes much longer than that of stem cells. [13] In many cases, the engraftment time depends on the cell dose, or the amount of stem cells obtained in the sample of blood. [13] In Dr. Moise's article about umbilical cord blood, it was found that there is approximately 10% less stem cells in cord blood than there is in bone marrow. [13] [14] Therefore, a sufficient amount of cord blood must be obtained in order to collect an adequate cell dose, however this amount varies from infant to infant and is irreplaceable. Given that this idea is quite new, there is still a lot of research that needs to be completed. For example, it is still unknown how long cord blood can safely be frozen without losing its beneficial effects. [13] There is a lower incidence with cord blood compared with traditional HSCT, despite less stringent HLA match requirements. [11]

Collection and storage

Umbilical cord blood is the blood left over in the placenta and in the umbilical cord after the birth of the baby. 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. [15] 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. [16]

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. [17]

History

The first successful cord blood transplant (CBT) was done in 1988 in a child with Fanconi anemia. [11] Early efforts to use CBT in adults led to mortality rates of about 50%, due somewhat to the procedure being done in very sick people, but perhaps also due to slow development of immune cells from the transplant. [11] By 2013, 30,000 CBT procedures had been performed and banks held about 600,000 units of cord blood. [12]

Society and culture

Regulation

The AABB has generated voluntary accreditation standards for cord blood banking facilities. [18]

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. [19] Several states also have regulations for cord blood banks. [18]

In Europe, Canada, and Australia use of cord blood is regulated as well. [18] 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. [20]

Private and public banks

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) ever use the umbilical cord blood that is stored. [21] The American Academy of Pediatrics 2007 Policy Statement on Cord Blood Banking stated: "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." and "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. [21] [22] The American Academy of Pediatrics also notes that the odds of using a person's own cord blood is 1 in 200,000 while the Institute of Medicine says that only 14 such procedures have ever been performed. [23]

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." [24] 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 transplantations come from public banks, rather than private banks, partly because most treatable conditions can't use a person's own cord blood. [25] [21] [22] [26] 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." [27]

The American Academy of Pediatrics, or AAP, 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. [28] 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". [29]

In March 2004, the European Union Group on Ethics (EGE) has issued Opinion No.19 titled Ethical Aspects of Umbilical Cord Blood Banking. [30] 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]

Research

Though uses of cord blood beyond blood and immunological disorders is speculative, some research has been done in other areas. [31] 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. [32] 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. [31] [32]

Along with cord blood, Wharton's jelly and the cord lining have been explored as sources for mesenchymal stem cells (MSC), and as of 2015 had been studied in vitro, in animal models, and in early stage clinical trials for cardiovascular diseases, as well as neurological deficits, liver diseases, immune system diseases, diabetes, lung injury, kidney injury, and leukemia. [33] [34] [35]

Cord blood is being used to get stem cells with which to test in people with type 1 diabetes mellitus. [36] The stem cells from umbilical cord blood are also being used in the treatment of a number of blood diseases including blood cancers. [37]

Cord blood is also being studied as a substitute for normal blood transfusions in the developing world. [37] [38] More research is necessary prior to the generalized utilization of cord blood transfusion. [37]

Cord blood stem cells are also being studied for treatment for COVID-19 cytokine storms since these and other perinatal (cord tissue and placental tissue derived) stem cells can secrete anti-inflammatory molecules. Dozens of clinical trials are under way to see if they can help patients with COVID-19. [39]

Recent clinical studies show that 1 year after the transplant of UM171 (a haematopoietic stem cell self-renewal agonist), transplant-related mortality was 5% and relapse incidence was at 21%. Furthermore, only 3 of 22 patients (~14%) who received the UM171-expanded cord blood transplantation died. [40] > [41]

A woman was reported to have been cured of HIV, the third person ever to be cured of the disease, using a transplantation of cord blood. Some of the details of the case were presented February 15, 2022 at the Conference on Retroviruses and Opportunistic Infections in Denver, CO. [42]

Related Research Articles

<span class="mw-page-title-main">Stem cell</span> Undifferentiated biological cells that can differentiate into specialized cells

In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell in a cell lineage. They are found in both embryonic and adult organisms, but they have slightly different properties in each. They are usually distinguished from progenitor cells, which cannot divide indefinitely, and precursor or blast cells, which are usually committed to differentiating into one cell type.

<span class="mw-page-title-main">Bone marrow</span> Semi-solid tissue in the spongy portions of bones

Bone marrow is a semi-solid tissue found within the spongy portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production. It is composed of hematopoietic cells, marrow adipose tissue, and supportive stromal cells. In adult humans, bone marrow is primarily located in the ribs, vertebrae, sternum, and bones of the pelvis. Bone marrow comprises approximately 5% of total body mass in healthy adult humans, such that a man weighing 73 kg (161 lbs) will have around 3.7 kg (8 lbs) of bone marrow.

<span class="mw-page-title-main">Umbilical cord</span> Conduit between embryo/fetus and the placenta

In placental mammals, the umbilical cord is a conduit between the developing embryo or fetus and the placenta. During prenatal development, the umbilical cord is physiologically and genetically part of the fetus and normally contains two arteries and one vein, buried within Wharton's jelly. The umbilical vein supplies the fetus with oxygenated, nutrient-rich blood from the placenta. Conversely, the fetal heart pumps low-oxygen, nutrient-depleted blood through the umbilical arteries back to the placenta.

<span class="mw-page-title-main">Hematopoietic stem cell transplantation</span> Medical procedure to replace blood or immune stem cells

Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce additional normal blood cells. It may be autologous, allogeneic or syngeneic.

<span class="mw-page-title-main">Graft-versus-host disease</span> Medical condition

Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants.

A cord blood bank is a facility which stores umbilical cord blood for future use. Both private and public cord blood banks have developed in response to the potential for cord blood in treating diseases of the blood and immune systems. Public cord blood banks accept donations to be used for anyone in need, and as such function like public blood banks. Traditionally, public cord blood banking has been more widely accepted by the medical community. Private cord blood banks store cord blood solely for potential use by the donor or donor's family. Private banks typically charge around $2,000 for the collection and around $200 a year for storage.

<span class="mw-page-title-main">Hematopoietic stem cell</span> Stem cells that give rise to other blood cells

Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the very first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within the (midgestational) aorta-gonad-mesonephros region, through a process known as endothelial-to-hematopoietic transition. In adults, haematopoiesis occurs in the red bone marrow, in the core of most bones. The red bone marrow is derived from the layer of the embryo called the mesoderm.

<span class="mw-page-title-main">CD34</span> Cluster of differentiation protocol that identifies cell surface antigens.

CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species.

<span class="mw-page-title-main">Regenerative medicine</span> Field of medicine involved in regenerating tissues

Regenerative medicine deals with the "process of replacing, engineering or regenerating human or animal cells, tissues or organs to restore or establish normal function". This field holds the promise of engineering damaged tissues and organs by stimulating the body's own repair mechanisms to functionally heal previously irreparable tissues or organs.

<span class="mw-page-title-main">Cell therapy</span> Therapy in which cellular material is injected into a patient

Cell therapy is a therapy in which viable cells are injected, grafted or implanted into a patient in order to effectuate a medicinal effect, for example, by transplanting T-cells capable of fighting cancer cells via cell-mediated immunity in the course of immunotherapy, or grafting stem cells to regenerate diseased tissues.

<span class="mw-page-title-main">Adult stem cell</span> Multipotent stem cell in the adult body

Adult stem cells are undifferentiated cells, found throughout the body after development, that multiply by cell division to replenish dying cells and regenerate damaged tissues. Also known as somatic stem cells, they can be found in juvenile, adult animals, and humans, unlike embryonic stem cells.

Stem-cell therapy uses stem cells to treat or prevent a disease or condition. As of 2016, the only established therapy using stem cells is hematopoietic stem cell transplantation. This usually takes the form of a bone marrow transplantation, but the cells can also be derived from umbilical cord blood. Research is underway to develop various sources for stem cells as well as to apply stem-cell treatments for neurodegenerative diseases and conditions such as diabetes and heart disease.

Autologous stem-cell transplantation is the autologous transplantation of stem cells—that is, transplantation in which stem cells are removed from a person, stored, and later given back to that same person.

Mesenchymal stem cells (MSCs) are multipotent cells found in multiple human adult tissues, including bone marrow, synovial tissues, and adipose tissues. Since they are derived from the mesoderm, they have been shown to differentiate into bone, cartilage, muscle, and adipose tissue. MSCs from embryonic sources have shown promise scientifically while creating significant controversy. As a result, many researchers have focused on adult stem cells, or stem cells isolated from adult humans that can be transplanted into damaged tissue.

<span class="mw-page-title-main">CFU-GEMM</span>

CFU-GEMM is a colony forming unit that generates myeloid cells. CFU-GEMM cells are the oligopotential progenitor cells for myeloid cells; they are thus also called common myeloid progenitor cells or myeloid stem cells. "GEMM" stands for granulocyte, erythrocyte, monocyte, megakaryocyte.

<span class="mw-page-title-main">Mesenchymal stem cell</span> Multipotent, non-hematopoietic adult stem cells present in multiple tissues

Mesenchymal stem cells (MSCs) also known as mesenchymal stromal cells or medicinal signaling cells, are multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts, chondrocytes, myocytes and adipocytes.

Adult mesenchymal stem cells are being used by researchers in the fields of regenerative medicine and tissue engineering to artificially reconstruct human tissue which has been previously damaged. Mesenchymal stem cells are able to differentiate, or mature from a less specialized cell to a more specialized cell type, to replace damaged tissues in various organs.

<span class="mw-page-title-main">Haematopoietic system</span>

The haematopoietic system is the system in the body involved in the creation of the cells of blood.

Cord lining, cord tissue, or umbilical cord lining membrane, is the outermost layer of the umbilical cord. As the umbilical cord itself is an extension of the placenta, the umbilical cord lining membrane is an extension of the amniotic membrane covering the placenta. The umbilical cord lining membrane comprises two layers: the amniotic layer and the sub-amniotic layer. The umbilical cord lining membrane is a rich source of two strains of stem cells (CLSCs): epithelial stem cells (CLECs) and mesenchymal stem cells (CLMCs). Discovered by Singapore-based CellResearch Corporation in 2004, this is the best known source for harvesting human stem cells.

<span class="mw-page-title-main">Cells4Life</span> Stem cell bank

Cells4Life is a private stem cell bank based in the United Kingdom. It procures, processes and stores human umbilical cord blood and tissue samples that may be used for stem cell treatments. Cells4Life is the largest provider of umbilical cord blood banking services in the UK, with over 50% of the UK market. Based in Burgess Hill, the company also provides umbilical stem cell storage and collection services in Spain, Italy, United Arab Emirates, Bulgaria, Pakistan and Kenya.

References

  1. ↑ "Allocord- human cord blood hematopoietic progenitor cell injection, solution". DailyMed. 13 February 2018. Retrieved 19 November 2022.
  2. ↑ "Clevecord (hpc- hematopoietic progenitor cell, cord blood injection, suspension". DailyMed. 25 April 2017. Retrieved 19 November 2022.
  3. ↑ "Cordcyte- human cord blood hematopoietic progenitor cell injection, suspension". DailyMed. 20 December 2015. Retrieved 19 November 2022.
  4. ↑ "Ducord- human cord blood hematopoietic progenitor cell solution". DailyMed. 4 November 2015. Retrieved 19 November 2022.
  5. ↑ "Hemacord- human cord blood hematopoietic progenitor cell injection". DailyMed. 19 October 2022. Retrieved 19 November 2022.
  6. 1 2 Pranke P, Failace RR, Allebrandt WF, Steibel G, Schmidt F, Nardi NB (2001). "Hematologic and immunophenotypic characterization of human umbilical cord blood". Acta Haematologica. 105 (2): 71–76. doi:10.1159/000046537. PMID   11408707. S2CID   30909026.
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  9. ↑ Riggan K (31 March 2009). "Cord Blood Stem Cells: An Overview | The Center for Bioethics & Human Dignity". Dignitas. 16 (1): 6–7. Archived from the original on 9 December 2018. Retrieved 9 December 2018. pluripote
  10. ↑ "How do embryonic stem cells, somatic stem cells, and cord blood stem cells differ? | NYSTEM". stemcell.ny.gov. Retrieved 9 December 2018. plurip
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  12. 1 2 Ballen KK, Gluckman E, Broxmeyer HE (July 2013). "Umbilical cord blood transplantation: the first 25 years and beyond". Blood. 122 (4): 491–498. doi:10.1182/blood-2013-02-453175. PMC   3952633 . PMID   23673863.
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  15. ↑ Mousavi SH, Zarrabi M, Abroun S, Ahmadipanah M, Abbaspanah B (2019). "Umbilical cord blood quality and quantity: Collection up to transplantation". Asian Journal of Transfusion Science. 13 (2): 79–89. doi: 10.4103/ajts.AJTS_124_18 . PMC   6910041 . PMID   31896912.
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  30. 1 2 "Opinion No. 19" (PDF). Archived from the original (PDF) on 2007-12-01., European Union Group on Ethics
  31. 1 2 Walther MM (2009). "Chapter 39. Cord Blood Hematopoietic Cell Transplantation". In Appelbaum FR, Forman SJ, Negrin RS, Blume KG (eds.). Thomas' hematopoietic cell transplantation stem cell transplantation (4th ed.). Oxford: Wiley-Blackwell. ISBN   978-1-4443-0353-7.
  32. 1 2 Haller MJ, Viener HL, Wasserfall C, Brusko T, Atkinson MA, Schatz DA (June 2008). "Autologous umbilical cord blood infusion for type 1 diabetes". Experimental Hematology. 36 (6): 710–715. doi:10.1016/j.exphem.2008.01.009. PMC   2444031 . PMID   18358588.
  33. ↑ Caseiro AR, Pereira T, Ivanova G, Luís AL, Maurício AC (2016). "Neuromuscular Regeneration: Perspective on the Application of Mesenchymal Stem Cells and Their Secretion Products". Stem Cells International. 2016: 9756973. doi: 10.1155/2016/9756973 . PMC   4736584 . PMID   26880998.
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  39. ↑ Wu KJ, Zimmer C, Corum J (July 16, 2020). "Coronavirus Drug and Treatment Tracker". The New York Times.
  40. ↑ Cohen S, Bambace N, Ahmad I, Roy J, Tang X, Zhang MJ, et al. (October 2023). "Improved outcomes of UM171-expanded cord blood transplantation compared with other graft sources: real-world evidence". Blood Advances. 7 (19): 5717–5726. doi: 10.1182/bloodadvances.2023010599 . PMC   10539875 . PMID   37467030.
  41. ↑ Cohen S, Roy J, Lachance S, Delisle JS, Marinier A, Busque L, et al. (February 2020). "Hematopoietic stem cell transplantation using single UM171-expanded cord blood: a single-arm, phase 1-2 safety and feasibility study". The Lancet. Haematology. 7 (2): e134–e145. doi:10.1016/S2352-3026(19)30202-9. PMID   31704264.
  42. ↑ Mandavilli A (2022-02-15). "A Woman Is Cured of H.I.V. Using a Novel Treatment". The New York Times. Retrieved 2022-02-16.


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