CHAPTER


DOI :10.26650/B/LS17LS30.2025.038.009   IUP :10.26650/B/LS17LS30.2025.038.009    Full Text (PDF)

Current Approach to the Properties, Uses and Immunology of Cord Blood Cells

Demet Kıvanç İzgiEkin Ece Gürer KlugeÇiğdem Kekik Çınar

Umbilical cord blood (UCB) is an important source of life, providing the nutrients and oxygen necessary for the development of the fetus. In addition, immune cells in the UCB, which connects the mother and the fetus and helps the development of the fetus, have a critical role in this development process. Cord blood stem cells (CBSCs) were also included in therapeutic applications for the first time in 1972 for the treatment of a case with lymphoblastic leukemia. Fetal umbilical CBSCs are used in the treatment of blood, immune system and some metabolic storage diseases in children and young adults today, from the classical bone marrow in the treatment of blood, immune system and some metabolic storage diseases, because they are easier to obtain, do not impose an additional burden on the donor, do not require full tissue compatibility for successful transplantation and have a low tissue rejection rate. It has become an alternative to stem cell transplants. Apart from these, clinical studies for the use of CBSCs in the treatment of hereditary biochemical and metabolic diseases, type 1 diabetes and immune system diseases, and experimental studies for the use of neurological diseases and regenerative medicine are ongoing.



References

  • 1. Exalto N Early human nutrition Eur J Obstet Gynecol Reprod Biol 1995;61(1):3-6 google scholar
  • 2. Di Naro E, Ghezzi F, Raio L, Franchi M, D’Addario V Umbilical cord morphology and pregnancy outcome Eur J Obstet Gynecol Reprod Biol 2001;96(2):150-7 google scholar
  • 3. Chaurasia BD, Agarwal BM Helical structure of the human umbilical cord Acta Anatomica 1979;103(2):226-30 google scholar
  • 4. Currarino G, Stannard MW, Kolni H Umbilical vein draining into the inferior vena cava via the internal iliac vein, bypassing the liver Pediatric Radiology 1991;21(4):265-6 google scholar
  • 5. Pranke P, Failace RR, Allebrandt WF, Steibel G, Schmidt F, Nardi NB Hematologic and immunophenotypic characterization of human umbilical cord blood Acta Haematol 2001;105(2):71-6 google scholar
  • 6. Newcomb JD, Sanberg PR, Klasko SK, Willing AE Umbilical cord blood research: current and future perspectives Cell Transplant 2007;16(2):151-8 google scholar
  • 7. Gluckman E, Rocha V, Chastang C Cord blood stem cells biology and transplantation Eurocord Meeting Saint Dominique, Paris, 1998:256-65 google scholar
  • 8. Cohen SB, Dominiguez E, Lowdell M, Madrigal JA The immunological properties of cord blood: overview of current research presented at the 2nd EUROCORD workshop Bone Marrow Transplant 1998;22:22-5 google scholar
  • 9. Francese R, Fiorina P Immunological and regenerative properties of cord blood stem cells Clin Immunol 2010;136(3):309-22 google scholar
  • 10. Cairo MS, Wagner JE Placental and/or umbilical cord blood: an alternative source of hematopoietic stem cells for transplantation Blood 1997;90(12):4665-78 google scholar
  • 11. Ende M, Ende N Hematopoietic transplantation by means of fetal (cord) blood A new method Va Med Mon (1918) 1972;99(3):276-80 google scholar
  • 12. Christensen RD Hematopoiesis in the fetus and neonate Pediatr Res 1989;26(6):531-5 google scholar
  • 13. Gluckman E, Rocha V History of the clinical use of umbilical cord blood hematopoietic cells Cytotherapy 2005;7(3):219-27 google scholar
  • 14. Broxmeyer HE. Biology of cord blood cells and future prospects for enhanced clinical benefit. Cytotherapy. 2005;7(3):209-18. google scholar
  • 15. Cairo MS, Suen Y, Knoppel E, van de Ven C, Nguyen A, Sender L. Decreased stimulated GM-CSF production and GM-CSF gene expression but normal numbers of GM-CSF receptors in human term newborns compared with adults. Pediatr Res. 1991;30(4):362-7. google scholar
  • 16. Chang M, Suen Y, Lee SM, Baly D, Buzby JS, Knoppel E, et al. Transforming growth factor-beta 1, macrophage inflammatory protein-1 alpha, and interleukin-8 gene expression is lower in stimulated human neonatal compared with adult mononuclear cells. Blood. 1994;84(1):118-24. google scholar
  • 17. Harris DT, Schumacher MJ, Locascio J, Besencon FJ, Olson GB, DeLuca D, et al. Phenotypic and functional immaturity of human umbilical cord blood T lymphocytes. Proc Natl Acad Sci USA. 1992;89(21):10006-10. google scholar
  • 18. Griffiths-Chu S, Patterson JA, Berger CL, Edelson RL, Chu AC. Characterization of immature T cell subpopulations in neonatal blood. Blood. 1984;64(1):296-300. google scholar
  • 19. Hassan J, Reen DJ. Cord blood CD4+ CD45RA+ T cells achieve a lower magnitude of activation when compared with their adult counterparts. Immunology. 1997;90(3):397-401. google scholar
  • 20. Tanaka H, Kai S, Yamaguchi M, Misawa M, Fujimori Y, Yamamoto M, et al. Analysis of natural killer (NK) cell activity and adhesion molecules on NK cells from umbilical cord blood. Eur J Haematol. 2003;71(1):29-38. google scholar
  • 21. Sorg RV, Kogler G, Wernet P. Identification of cord blood dendritic cells as an immature " CD11c- population. Blood. 1999;93(7):2302-07. google scholar
  • 22. Moser M, Murphy KM. Dendritic cell regulation of TH1-TH2 development. Nat Immunol. 2000;1(3):199-205. google scholar
  • 23. Sano H, Wakui A, Kawachi M, Kato R, Moriyama S, Nishikata M, et al. Profiling of microbiota in liquid baby formula consumed with an artificial nipple. Biomed Res. 2019;40(4):163-8. google scholar
  • 24. Lederberg J, McCray AT. Ome sweet Omics - a genealogical treasury of words. Scientist. 2001;15(7):8. google scholar
  • 25. Kho ZY, Lal SK. The human gut microbiome - A potential controller of wellness and disease. Front Microbiol. 2018;9:1835. google scholar
  • 26. Collado MC, Rautava S, Aakko J, Isolauri E, Salminen S. Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid. Sci Rep. 2016;6:23129. google scholar
  • 27. Su M, Nie Y, Shao R, Duan S, Jianğ Y, Wanğ M, et al. Diversified ğut microbiota in newborns of mothers with ğestational diabetes mellitus. PLoS One. 2018;13(10):e0205695. google scholar
  • 28. Bushman FD. De-discovery of the placenta microbiome. Am J Obstet Gynecol. 2019;220(3):213-4. google scholar
  • 29. Çox LM, Blaser MJ. Antibiotics in early life and obesity. Nat Rev Endocrinol. 2015;11(3):182-190. google scholar
  • 30. Yockey LJ, Iwasaki A. Interferons and proinflammatory cytokines in preğnancy and fetal development. Immunity. 2018;49(3):397-412. google scholar
  • 31. Mozurkewich EL, Berman DR, Vahratian A, Çlinton ÇM, Romero VÇ, Çhilimiğras JL, et al. Effect of prenatal EPA and DHA on maternal and umbilical cord blood cytokines. BMÇ Preğnancy Çhildbirth. 2018;18(1):261. google scholar
  • 32. Rio-Aiğe K, Azağra-Boronat I, Massot-Çladera M, Selma-Royo M, Parra-Llorca A, Gonzalez S, et al. Association of Maternal microbiota and diet in cord blood cytokine ' and immunoğlobulin profiles. Int J Mol Sci. 2021;22(4):1778. google scholar
  • 33. Jimenez E, Fern ' andez L, Mar ' 'ın ML, Mart'ın R, Odriozola JM, Nueno-Palop Ç, et al. Isolation of commensal bacteria from umbilical cord blood of healthy neonates born by cesarean section. Çurr Microbiol. 2005;51(4):270-4. google scholar
  • 34. Van Lieshout RJ, Krzeczkowski JE. Just DO(HaD) It! Testinğ the clinical potential of the DOHaD hypothesis to prevent mental disorders usinğ experimental study desiğns. J Dev Oriğ Health Dis. 2016;7(6):565-73. google scholar
  • 35. Hassiotou F, Geddes DT. Immune cell-mediated protection of the mammary ğland and the infant durinğ breastfeedinğ. Adv Nutr. 2015;6(3):267-75. google scholar
  • 36. Matsumiya Y, Kato N, Watanabe K, Kato H. Molecular epidemioloğical study of vertical transmission of vağinal lactobacillus species from mothers to newborn infants in Japanese, by arbitrarily primed polymerase chain reaction. J Infect Çhemother. 2002;8(1):43-9. google scholar
  • 37. Martin R, Lanğa S, Revirieğo Ç, Jimınez E, Marın ML, Xaus J, et al. Human milk is a source of lactic acid bacteria for the infant ğut. J Pediatr. 2003;143(6):754-8. google scholar
  • 38. Makino H, Kushiro A, Ishikawa E, Gawad A, Sakai T, Oishi K,et al. Mother-to-infant transmission of intestinal bifidobacterial strains has an impact on the early development of vaginally delivered infant’s microbiota. PLoS One. 2013;8(11):e78331. google scholar
  • 39. MariBen J, HaiB A, Meyer C, Van Rossum T, B"unte LM, Frommhold D, et al. Efficacy of bifidobacterium longum, B. infantis and lactobacillus acidophilus probiotics to prevent gut dysbiosis in preterm infants of 28+0-32+6 weeks of gestation: a randomised, placebo-controlled, double-blind, multicentre trial: the PRIMAL clinical study protocol [published correction appears in BMJ Open. 2019;9(11):e032617. google scholar
  • 40. Schei K, Avershina E, 0ien T, Rudi K, Follestad T, Salamati S, et al. Early gut mycobiota and mother-offspring transfer. Microbiome. 2017;5(1):107. google scholar
  • 41. Collado MC, Rautava S, Aakko J, Isolauri E, Salminen S. Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid. Sci Rep. 2016;6:23129. google scholar
  • 42. Yang J, Fan H, Hao J, Ren Y, Chen L, Li G, et al. Amelioration of acute graft-versus-host disease by adoptive transfer of ex vivo expanded human cord blood CD4+CD25+ forkhead box protein 3+ regulatory T cells is associated with the polarization of Treg/Th17 balance in a mouse model. Transfusion. 2012;52(6):1333-47. google scholar
  • 43. van Heeckeren WJ, Fanning LR, Meyerson HJ, Fu P, Lazarus HM, Cooper BW, et al. Influence of human leucocyte antigen disparity and graft lymphocytes on allogeneic engraftment and survival after umbilical cord blood transplant in adults. Br J Haematol. 2007;139(3):464-74. google scholar
  • 44. Davies JE, Walker JT, Keating A. Concise Review: Wharton’s Jelly: The rich, but enigmatic, source of mesenchymal stromal cells. Stem Cells Transl Med. 2017;6(7):1620-30. google scholar
  • 45. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143-7. google scholar
  • 46. Le Blanc K, Tammik L, Sundberg B, Haynesworth SE, Ringden O. Mesenchymal ' stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol. 2003;57(1):11-20. google scholar
  • 47. Kita K, Gauglitz GG, Phan TT, Herndon DN, Jeschke MG. Isolation and characterization of mesenchymal stem cells from the sub-amniotic human umbilical cord lining membrane. Stem Cells Dev. 2010;19(4):491-502. google scholar
  • 48. Ljungman P, Bregni M, Brune M, Cornelissen J, de Witte T, Din G, et al. Alloğeneic and autoloğous transplantation for haematoloğical diseases, solid tumours and immune disorders: current practice in Europe 2009. Bone Marrow Transplant. 2010;45(2):219-34. google scholar
  • 49. Mayani H. Bioloğical differences between neonatal and adult human hematopoietic stem/proğenitor cells. Stem Çells Dev. 2010;19(3):285-98. google scholar
  • 50. Francese R, Fiorina P. Immunoloğical and reğenerative properties of cord blood stem cells. Çlin Immunol. 2010;136(3):309-22. google scholar
  • 51. Yamağuchi TP, Dumont DJ, Çonlon RA, Breitman ML, Rossant J. flk-1, an flt-related receptor tyrosine kinase is an early marker for endothelial cell precursors. Development. 1993;118(2):489-98. google scholar
  • 52. Lucchinetti E, Zeisberğer SM, Baruscotti I, Wacker J, Fenğ J, Zauğğ K, et al. Stem cell-like human endothelial proğenitors show enhanced colony-forminğ capacity after brief sevoflurane exposure: preconditioninğ of anğioğenic cells by volatile anesthetics. Anesth Analğ. 2009;109(4):1117-26. google scholar
  • 53. Doan PL, Frei AÇ, Piryani SO, Szalewski N, Fan E, Himburğ HA. Çord blood-derived endothelial proğenitor cells promote in vivo reğeneration of human hematopoietic bone marrow. Int J Radiat Oncol Biol Phys. 2023;116(5):1163-74. google scholar
  • 54. Reddi AS, Kothari N, Kuppasani K, Ende N. Human umbilical cord blood cells and diabetes mellitus: recent advances. Çurr Stem Çell Res Ther. 2015;10(3):266-70. google scholar
  • 55. Stiner R, Alexander M, Liu G, Liao W, Liu Y, Yu J, et al. Transplantation of stem cells from umbilical cord blood as therapy for type I diabetes. Çell Tissue Res. 2019;378(2):155-62. google scholar
  • 56. Çai J, Wu Z, Xu X, Liao L, Çhen J, Huanğ L, et al. Ümbilical cord mesenchymal stromal cell with autoloğous bone marrow cell transplantation in established type 1 diabetes: A pilot randomized controlled open-label clinical study to assess safety and impact on insulin secretion. Diabetes Çare. 2016;39(1):149-57. google scholar
  • 57. Zhao Y, Jianğ Z, Zhao T, YeM, HuÇ, Zhou H, et al. Tarğetinğ insulin resistance in type 2 diabetes via immune modulation of cord blood-derived multipotent stem cells (ÇB-SÇs) in stem cell educator therapy: phase I/II clinical trial. BMÇ Med. 2013;11:160. google scholar
  • 58. Parkinson-Lawrence EJ, Shandala T, Prodoehl M, Plew R, Borlace GN, Brooks DA. Lysosomal storağe disease: revealinğ lysosomal function and physioloğy. Physioloğy (Bethesda). 2010;25(2):102-15. google scholar
  • 59. Mahmoud HK, Elhaddad AM, Fahmy OA, Samra MA, Abdelfattah RM, El-Nahass YH, et al. Allogeneic hematopoietic stem cell transplantation for non-malignant hematological disorders. J Adv Res. 2015;6(3):449-58. google scholar
  • 60. Eapen M, Rubinstein P, Zhang MJ, Stevens C, Kurtzberg J, Scaradavou A, et al. Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study. Lancet. 2007;369(9577):1947-54. google scholar
  • 61. Wang L, Wang L, Cong X, Liu G, Zhou J, Bai B, et al. Human umbilical cord mesenchymal stem cell therapy for patients with active rheumatoid arthritis: safety and efficacy. Stem Cells Dev. 2013;22(24):3192-202. google scholar
  • 62. Xiao J, Nan Z, Motooka Y, Low WC. Transplantation of a novel cell line population of umbilical cord blood stem cells ameliorates neurological deficits associated with ischemic brain injury. Stem Cells Dev. 2005;14(6):722-33. google scholar
  • 63. Ende N, Chen R. Parkinson’s disease mice and human umbilical cord blood. J Med. 2002;33(1-4):173-80. google scholar
  • 64. Wang Y, Ji X, Leak RK, Chen F, Cao G. Stem cell therapies in age-related neurodegenerative diseases and stroke. Ageing Res Rev. 2017;34:39-50. google scholar
  • 65. Xie ZH, Liu Z, Zhang XR, Yang H, Wei LF, Wang Y, et al. Wharton’s Jelly-derived mesenchymal stem cells alleviate memory deficits and reduce amyloid- deposition in an APP/PS1 transgenic mouse model. Clin Exp Med. 2016;16(1):89-98. google scholar
  • 66. Yang H, Yang H, Xie Z, Wei L, Bi J. Systemic transplantation of human umbilical cord derived mesenchymal stem cells-educated T regulatory cells improved the impaired cognition in APPswe/PS1dE9 transgenic mice. PLoS One. 2013;8(7):e69129. google scholar
  • 67. Morioka C, Komaki M, Taki A, Honda I, Yokoyama N, Iwasaki K, et al. Neuroprotective effects of human umbilical cord-derived mesenchymal stem cells on periventricular leukomalacia-like brain injury in neonatal rats. Inflamm Regen. 2017;37:1. google scholar
  • 68. Beeravolu N, Khan I, McKee C, Dinda S, Thibodeau B, Wilson G Chaudhry GR. Isolation and comparative analysis of potential stem/progenitor cells from different regions of human umbilical cord. Stem Cell Res. 2016;16(3):696-711. google scholar
  • 69. Musina RA, Bekchanova ES, Belyavskii AV, Grinenko TS, Sukhikh GT. Umbilical cord blood mesenchymal stem cells. Bull Exp Biol Med. 2007;143(1):127-31. google scholar
  • 70. Lee DH, Kim SA, Song JS, Shetty AA, Kim BH, Kim SJ. Cartilage regeneration using human umbilical cord blood derived mesenchymal Stem Cells: A systematic review and meta-analysis. Medicina (Kaunas). 2022;58(12):1801. google scholar
  • 71. Hirata Y, Sata M, Motomura N, Takanashi, M., Suematsu, Y., Ono, M. et al. Human umbilical cord blood cells improve cardiac function after myocardial infarction. Biochem Biophys Res Çommun. 2005;327(2):609-614. google scholar
  • 72. Joyce NÇ, Harris DL, Markov V, Zhanğ Z, Saitta B. Potential of human umbilical cord blood mesenchymal stem cells to heal damağed corneal endothelium. Mol Vis. 2012;18:547-564. google scholar
  • 73. Zhilai Z, Hui Z, Anmin J, Shaoxionğ M, Bo Y, Yinhai Ç. A combination of taxol infusion and human umbilical cord mesenchymal stem cells transplantation for the treatment of rat spinal cord injury. Brain Res. 2012;1481:79-89. google scholar
  • 74. Zeinali R, Biazar E, Keshel SH, Tavirani MR, Asadipour K. Reğeneration of full-thickness skin defects usinğ umbilical cord blood stem cells loaded into modified porous scaffolds. ASAIO J. 2014;60(1):106-14. google scholar
  • 75. Ghodsizad A, Fahy BN, Waclawczyk S, Liedtke S, Berjon JMG, Barrios R, et al. Portal application of human unrestricted somatic stem cells to support hepatic reğenerationm after portal embolization and tumor surğery. ASAIO J. 2012;58(3):255-61. google scholar
  • 76. Gonzalez F, Bou ' e S, Izpis 'ua Belmonte JÇ. Methods for making induced pluripotent ' stem cells: reprogramming a la carte. Nat Rev Genet. 2011;12(4):231-42. ‘ google scholar
  • 77. Rim YA, Nam Y, Ju JH. Application of cord blood and cord blood-derived induced pluripotent stem cells for cartilage regeneration. Çell Transplant. 2019;28(5):529-37. google scholar
  • 78. Medhekar SK, Shende VS, Çhincholkar AB. Recent stem cell advances: cord blood and induced pluripotent stem cell for cardiac regeneration- a review. Int J Stem Çells. 2016;9(1):21-30. google scholar
  • 79. Singh VK, Kalsan M, Kumar N, Saini A, Çhandra R. Induced pluripotent stem cells: applications in regenerative medicine, disease modeling, and drug discovery. Front Çell Dev Biol. 2015;3:2. google scholar
  • 80. Zhang L, Hu J, Athanasiou KA. The role of tissue engineering in articular cartilage repair and regeneration. Çrit Rev Biomed Eng. 2009;37(1-2):1-57. google scholar
  • 81. Nam Y, Rim YA, Jung SM, Ju JH. Çord blood cell-derived iPSÇs as a new candidate for chondrogenic differentiation and cartilage regeneration. Stem Çell Res Ther. 2017;8(1):16. google scholar
  • 82. Park TS, Bhutto I, Zimmerlin L, Huo JS, Nagaria P, Miller D, et al. Vascular progenitors from cord blood-derived induced pluripotent stem cells possess augmented capacity for regenerating ischemic retinal vasculature. Çirculation. 2014;129(3):359-72. google scholar


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