Abstract
Cellular therapy is a compelling and potential treatment for certain neurological and neurodegenerative diseases as well as a viable treatment for acute injury to the spinal cord and brain. The hematopoietic system offers alternative sources for stem cells compared to those of fetal or embryonic origin. Bone marrow stromal and umbilical cord cells have been used in pre-clinical models of brain injury, directed to differentiate into neural phenotypes, and have been related to functional recovery after engraftment in central nervous system (CNS) injury models. This paper reviews the advantages, utilization and progress of human umbilical cord blood (HUCB) cells in the neural cell transplantation and repair field.
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Bicknese AR, HS Goodwin, CO Quinn and CD Verneake (2002) Human umbilical cord blood cells can be induced to express markers for neurons and glia.Cell Transplantation 11(3), 261–264.
Blau HM, TR Brazelton and JM Weimann (2001) The evolving concept of a stem cell: entity or function?Cell 105, 829–841.
Broxmeyer HE (1995) Growth factors and cord blood stem and progenitor cells.Immunol. Invest. 24, 391–402.
Broxmeyer HE (1996) Primitive hematopoietic stem and progenitor cells in human umbilical cord blood: an alternative source of transplantable cells.Cancer Treat. Res. 84, 139–148.
Broxmeyer HE (1998)Cellular Characteristics of Cord Blood and Cord Blood Transplantation (AABB Press, Bethesda, MD).
Broxmeyer HE and S Cooper (1997) High-efficiency recovery of immature haematopoietic progenitor cells with extensive proliferative capacity from human cord blood cryopreserved for 10 years.Clin. Exp. Immunol. 107 Suppl. 1, 45–53.
Broxmeyer HE, GW Douglas, G Hangoc, S Cooper, J Bard, D English, M Arny, L Thomas and EA Boyse (1989) Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells.Proc. Natl. Acad. Sci. USA 86(10), 3828–3832.
Broxmeyer HE, E Gluckman, A Auerbach, GW Douglas, H Friedman, S Cooper, G Hangoc, J Kurtzberg, J Bard and EA Boyse (1990) Human umbilical cord blood: a clinically useful source of transplantable hematopoietic stem/pro genitor cells.Int. J. Cell Cloning 8 (Suppl. 1), 76–89; discussion pp. 89–91.
Broxmeyer HE, J Kurtzberg, E Gluckman, AD Auerbach, G Douglas, S Cooper, JH Falkenburg, J Bard and EA Boyse (1991) Umbilical cord blood hematopoietic stem and repopulating cells in human clinical transplantation.Blood Cells 17(2), 313–329.
Broxmeyer HE, S Cooper, M Yoder and G Hangoc (1992a) Human umbilical cord blood as a source of transplantable hematopoietic stem and progenitor cells.Curr. Top. Microbiol. Immunol. 177, 195–204.
Broxmeyer HE, G Hangoc, S Cooper, RC Ribeiro, V Graves, M Yoder, J Wagner, S Vadhan-Raj, L Benninger, P Rubinsteinet al. (1992b) Growth characteristics and expansion of human umbilical cord blood and estimation of its potential for transplantation in adults.Proc. Natl. Acad. Sci. USA,89(9), 4109–4113.
Broxmeyer HE, EF Srour, G Hangoc, S Cooper, SA Anderson and DM Bodine (2003) High-efficiency recovery of functional hematopoietic progenitor and stem cells from human cord blood cryopreserved for 15 years.Proc. Natl. Acad. Sci. USA 100, 645–650.
Buzanska L, EK Machaj, B Zablocka, Z Pojda and K Domanska-Janik (2002) Human cord blood-derived cells attain neuronal and glial featuresin vitro.J. Cell Sci. 115(Pt 10), 2131–2138.
Caims J (1975) Mutation selection and the natural history of cancer.Nature,255(5505), 197–200.
Cardoso AA, ML Li, P Batard, A Hatzfeld, EL Brown, JP Levesque, H Sookdeo, B Panterne, P Sansilvestri, SC Clarket al. (1993a) Release from quiescence of CD34+ CD38− human umbilical cord blood cells reveals their potentiality to engraft adults.Proc. Natl. Acad. Sci. USA 90(18), 8707–8711.
Cardoso AA, ML Li, P Batard, P Sansilvestri, A Hatzfeld, JP Levesque, JS Lebkowski and J Hatzfeld (1993b) Human umbilical cord blood CD34+ cell purification with high yield of early progenitors.J. Hematother. 2(2), 275–279.
Carpenter MK, MS Inokuma, J Denham, T Mujtaba, CP Chiu and MS Rao (2001) Enrichment of neurons and neural precursors from human embryonic stem cells.Exp. Neurol. 172, 383–397.
Chen J, PR Sanberg, Y Li, L Wang, M Lu, AE Willing, J Sanchez-Ramos and M Chopp (2001) Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats.Stroke 32(11), 2682–2688.
Clinical Trials (2003) http://www.clinicaltrials.gov.
Cohen RI, R McKay and G Almazan (1999) Cyclic AMP regulates PDGF-stimulated signal transduction and differentiation of an immortalized optic-nerve-derived cell line.J. Exp. Biol. 202 (Pt. 4): 461–473.
Dietrich J, M Noble and M Mayer-Proschel (2002) Characterization of A2B5+ glial precursor cells from cryopreserved human fetal brain progenitor cells.Glia 40, 65–77.
Eaton MJ and SR Whittemore (1996) Autocrine BDNF secretion enhances the survival and serotonergic differentiation of raphe neuronal precursor cells grafted into the adult rat CNS.Exp. Neurol. 140, 105–114.
Erices A, P Conget and JJ Minguell (2000). Mesenchymal progenitor cells in human umbilical cord blood.Br. J. Haematol. 109(1), 235–242.
Gage FH (1998) Cell therapy.Nature 392, 18–24.
Gage FH (2000) Mammalian neural stem cells.Science 287, 1433–1438.
Garbuzova-Davis S, A Willing, T Zigova, S Saporta, EB Justen, JC Lane, JE Hudson, N Chen, CD Hart and PR Sanberg (2003) Intravenous administration of human umbilical cord blood cells in a mouse model of ALS: distribution, migration, and differentation.J. Hematother. and Stem Cell Res. 12(3), 255–270.
Ghen M (2003) Institute of Cellular Medicine http://www.alshucb.org
Gluckman E (2001) Hematopoietic Stem-Cell Transplants Using Umbilical-Cord Blood.N. Engl. J. Med. 344, 1860–1861.
Gluckman E, HA Broxmeyer, AD Auerbach, HS Friedman, GW Douglas, A Devergie, H Esperou, D Thierry, G, Socie, P Lehnet al. (1989) Hematopoietic reconstitution in a patient with Fanconi's anemia by means of umbilical-cord blood from an HLA-identical sibling.N. Engl. J. Med. 321(17), 1174–1178.
Gluckman E, V Rocha, A Boyer-Chammard, F Locatelli, W Arcese, R Pasquini, J Ortega, G Souillet, E Ferreira, JP Laporte, M Fernandez and C Chastang (1997). Outcome of cord-blood transplantation from related and unrelated donors. Eurocord Transplant Group and the European Blood and Marrow Transplantation Group.N. Engl. J. Med. 337(6), 373–381.
Gluckman E, V Rocha and C Chastang, (1999) Peripheral stem cells in bone marrow transplantation. Cord blood stem cell transplantation.Baillieres Best Pract. Res. Clin. Haematol. 12, 279–292.
Gritti A, P Frolichsthal-Schoeller, R Galli, EA Parati, L Cova, SF Pagano, CR Bjomson, and AL Vescovi (1999) Epidermal and fibroblast growth factors behave as mitogenic regulators for a single multipotent stem cell-like population from the subventricular region of the adult mouse forebrain.J. Neurosci. 19, 3287–3297.
Ha Y, JU Choi, DH Yoon, DS Yeon, JJ Lee, HO Kim and YE Cho (2001) Neural phenotype expression of cultured human cord blood cellsin vitro.Neuro Report 12, 3523–3527.
Hampton A (2002) Hope at Duke for children with Sanfilippo syndrome. www.abc11tv.com, Nov. 25.
Healy L, G May, K Gale, F Grosveld, M Greaves and T Enver (1995) The stern cell antigen CD34 functions as a regulator of hemopoietic cell adhesion.Proc. Natl. Acad. Sci. USA 92(26), 12240–12244.
Hows JM, JC Marsh, BA Bradley, T Luft, L Coutinho, NG Testa and TM Dexter (1992) Human cord blood: a source of transplantable stem cells?Bone Marrow Transplant. 9 (Suppl. 1), 105–108.
Johansson CB, M Svensson, L Wallstedt, AM Janson and J Frisen (1999) Neural stem cells in the adult human brain.Exp. Cell Res. 253, 733–736.
Kempuraj D, H Saito, A Kaneko, K Fukagawa, M Nakayama, H Toru, M Tomikawa, H Tachimoto, M Ebisawa, A Akasawa, T Miyagi, H Kimura, T Nakajima, K Tsuji and T Nakahata (1999) Characterization of mast cell-committed progenitors present in human umbilical cord blood.Blood 93(10), 3338–3346.
Kinmond S, TC Aitchison, BM Holland, JG Jones, TL Turner and CA Wardrop (1993) Umbilical cord clamping and preterm infants: a randomised trial.Bmj 306, 172–175.
Kondo T and M Raff (2000) Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells.Science 289, 1754–1757.
Kukekov VG, ED Laywell, O Suslov, K Davies, B Scheffler, LB Thomas, TF O'Brien, M Kusakabe and DA Steindler (1999) Multipotent stem/progenitor cells with similar properties arise from two neurogenic regions of adult human brain.Exp. Neurol. 156, 333–344.
Lackie JM, JAT Dow and SE Blackshaw (1999)The Dictionary of Cell and Molecular Biology, 3rd Edition (Academic Press: San Diego).
Lajtha LG (1979) Haemopoietic stem cells: concept and definitions.Blood Cells 5, 447–455.
Lajtha LG (1980) Bone marrow: the seedbed of blood, inBlood, Pure and Eloquent (Wintrobe MM, Ed.), McGraw Hill: New York.
Lajtha LG (1983) Stem cell concepts, InStem Cells (Potten CS, Ed.), (Churchill Livingstone: New York).
Laughlin MJ, J Barker, B Bambach, O Koc, DA Rizzieri, JE Wagner, SL Gerson, HM Lazarus, M Cairo, CE Stevens, P Rubinstein and J Kurtzberg (2001) Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors.New Engl. J. Med. 344, 1815–1822.
Lendahl U, LB Zimmerman and RD McKay (1990) CNS stem cells express a new class of intermediate filament protein.Cell 60, 585–595.
Lobel DA, M Hadman, PR Sanberg and CV Borlongan (2003) Early intracerebral intra-arterial transplantation of human umbilical cord blood cells into an ischemic rat brain model.Exp. Neurol. 181(1), 97.
Lu D, PR Sanberg, A Mahmood, Y Li, L Wang, J Sanchez-Ramos and M Chopp (2002) Intravenous administration of human umbilical cord blood reduces neurological deficit in the rat after traumatic brain injury.Cell Transplant. 11(3), 275–281.
Lu L, M Xiao, RN Shen, S Grigsby and HE Broxmeyer (1993) Enrichment, characterization, and responsiveness of single primitive CD34 human umbilical cord blood hematopoietic progenitors with high proliferative and replating potential.Blood 81(1), 41–48.
Lu L, RN Shen and HE Broxmeyer (1996) Stem cells from bone marrow, umbilical cord blood and peripheral blood for clinical application: current status and future application.Crit. Rev. Oncol. Hematol. 22(2), 61–78.
Marshak DR, RL Gardner and D Gottlieb (2001)Stem Cell Biology (Vol. Monograph 40), Cold Spring Harbor Laboratory Press: Cold spring Harbor.
Mayani H and PM Lansdorp (1998) Biology of human umbilical cord blood-derived hematopoietic stem/progenitor cells.Stem Cells 16, 153–165.
Metcalf D (1984)Clonal Culture of Hemopoietic Cells: Techniques and Applications (Elsevier Science Publishers BV: The Netherlands).
Miraglia S, W Godfrey, AH Yin, K Atkins, R Warnke, JT Holden, RA Bray, EK Waller and DW Buck (1997) A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning.Blood 90, 5013–5021.
Mitsui H, T Furitsu, AM Dvorak, AM Irani, LB Schwartz, N Inagaki, M Takei, K Ishizaka, KM Zsebo, S Gilliset al. (1993) Development of human mast cells from umbilical cord blood cells by recombinant human and murine c-kit ligand.Proc. Natl. Acad. Sci. USA 90(2), 735–739.
Miyawaki T, N Moriya, T Nagaoki and N Taniguchi (1981) Maturation of B-cell differentiation ability and T-cell regulatory function in infancy and childhood.Immunol. Rev. 57, 61–87.
Mokry J and S Nemecek (1998) Angiogenesis of extra- and intraembryonic blood vessels is associated with expression of nestin in endothelial cells.Folia Biol. (Praha)44, 155–161.
Mujtaba T, DR Piper, A Kalyani, AK Groves, MT Lucero and MS Rao (1999) Lineage-restricted neural precursors can be isclated from both the mouse neural tube and cultured ES cells.Dev. Biol. 214, 113–127.
Nagaoki T, T Miyawaki, R Ciorbaru, A Yachie, N Uwadana, N Moriya and N Taniguchi (1981) Maturation of B cell differentiation ability and T cell regulatory function during child growth assessed in a Nocardia water scluble mitogen-driven system.J. Immunol. 126, 2015–2019.
National Center for Farmworker Health, Inc (N.C.F.H.) (2002)National Vital Statistics Reports, Centers for Disease Control and Prevention.
National Institutes of Health (NIH), Department of Health and Human Services (2001) Stem Cells: Scientific Progress And Future Research Directions, www.nih.gov/news/stemcell/scireport.htm.
National Marrow Donor Program (NMDP) (2003) http://www.marrow.org/MEDICAI./cord_blood_transplantation_advanced.html
Newman MB, TB Freeman, CD Hart and PR Sanberg (2003) Neural stem cells for cellular therapy in humans, inNeural Stem Cells: Development and Transplantation (Bottenstein JE, Ed.), (Kluwer Academic: NY), pp. 385–418.
Ogawa Y, K Sawamoto, T Miyata, S Miyao, M Watanabe, M Nakamura, BS Bregman, M Koike, Y Uchiyama, Y Toyama and H Okano (2002) Transplantation ofin vitro-expanded fetal neural progenitor cells results in neurogenesis and functional recovery after spinal cord contusion injury in adult rats.J. Neurosci. Res. 69, 925–933.
Orlic D, IJ Girard, SM Anderson, BK Do, NE Seidel, CT Jordan and DM Bodine (1997) Transduction efficiency of cell lines and hematopoietic stem cells correlates with retrovirus receptor mRNA levels.Stem Cells 15 (Suppl 1), 23–28; discussion, pp. 28–29.
Palmer TD, EA Markakis, AR Willhoite, F Safar and FH Gage (1999) Fibroblast growth factor-2 activates a latent neurogenic program in neural stem cells from diverse regions of the adult CNS.J. Neurosci. 19, 8487–8497.
Pan Y, H Zhang, R Bretton, WM Panneton and A Bicknese (2003) Intracarotid adiminstration of cultured non-hematopoietic human umbilical cord blood cells immediately after focal cerebral ischemia in rats.Exp. Neurol. 181(1), 102.
Poltavtseva RA, MV Marey, MA Aleksandrova, AV Revishchin, LI Korochkin and GT Sukhikh (2002) Evaluation of progenitor cell cultures from human embryos for neurotransplantation.Brain Res. Dev. Brain Res. 134, 149–154.
Potgens AJ, M Bolte, B Huppertz, P Kaufmann and HG Frank (2001) Human trophoblast contains an intracellular protein reactive with an antibody against CD133-a novel marker for trophoblast.Placenta 22, 639–645.
Potten CS (1983)Stem Cells: Their Identification and Characterisation (Churchill Livigstone: New York).
Rao MS and MP Mattson (2001) Stem cells and aging: expanding the possibilities.Mech. Ageing Dev. 122(7), 713–734.
Rappold I, BL Ziegler, I Kohler, S Marchetto, O Rosnet, D Birnbaum, PJ Simmons, AC Zannettino, B Hill, S Neu, W Knapp, R Alitalo, K Alitalo, A Ullrich, L Kanz and HJ Buhring (1997) Functional and phenotypic characterization of cord blood and bone marrow subsets expressing FLT3 (CD135) receptor tyrosine kinase.Blood 90, 111–125.
Redies C, U Lendahl and RD McKay (1991) Differentiation and heterogeneity in T-antigen immortalized precursor cell lines from mouse cerebellum.J. Neurosci. Res. 30, 601–615.
Reynolds BA and S Weiss (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system.Science 255, 1707–1710.
Sanchez-Ramos JR (2002) Neural cells derived from adult bone marrow and umbilical cord blood.J. Neurosci. Res. 69, 880–893.
Sanchez-Ramos J, S Song, F Cardozo-Pelaez, C Hazzi, T Stedeford, A Willing, TB Freeman, S Saporta, W Janssen, N Patel, DR Cooper and PR Sanberg (2000) Adult bone marrow stromal cells differentiate into neural cellsin vitro.Exp. Neurol. 164, 247–256.
Sanchez-Ramos JR, S Song, SG Kamath, T Zigova, A Willing, F Cardozo-Pelaez, T Stedeford, M Chopp and PR Sanberg (2001) Expression of neural markers in human umbilical cord blood.Exp. Neurol. 171(1), 109–115
Sanz GF, S Saavedra, D Planelles, L Senent, J Cervera, E Barragan, C Jimenez, L Larrea, G Martin, J Martinez, I Jarque, F Moscardo, G Plume, R Andreu, AI Regadera, I Garcia, S Molla, P Solves, J de la Rubia, P Bolufer, L Benlloch, MA Soler, ML Marty and MA Sanz (2001) Standardized, unrelated donor cord blood transplantation in adults with hematologic malignancies.Blood 98, 2332–2338.
Saporta S, JJ Kim, A Willing, ES Fu, CD Hart and PR Sanberg (2003) Human umbilical cord blood stem cells infusion in spinal cord injury.J. Hematother. and Stem Cell Res. 12(3), 271–278.
Shih CC, Y Weng, A Mamelak, T LeBon, MC Hu and SJ Forman (2001) Identification of a candidate human neurohematopoietic stem-cell population.Blood 98, 2412–2422.
Shihabuddin LS, TD Palmer and FH Gage (1999) The search for neural progenitor cells: prospects for the therapy of neurodegenerative disease.Mol. Med. Today 5, 474–480.
Steenblock DS (2003). http://www.strokedoctor.com/index.html.
Tamaki S, K Eckert, D He, R Sutton, M Doshe, G Jain, R Tushinski, M Reitsma, B Harris, A Tsukamoto, F Gage, I Weissman and N Uchida (2002) Engraftment of sorted/expanded human central nervous system stem cells from fetal brain.J. Neurosci. Res. 69, 976–986.
Thomas JW, C LaMantia and T Magnuson (1998) X-ray-induced mutations in mouse embryonic stem cells.Proc. Natl. Acad. Sci. USA 95, 1114–1119.
Thomson BG, KA Robertson, D Gowan, D Heilman, HE Broxmeyer, D Emanuel, P Kotylo, Z Brahmi and FO Smith (2000) Analysis of engraftment, graft-versus-host disease, and immune recovery following unrelated donor cord blood transplantation.Blood 96, 2703–2711.
Till JE and EA McCulloch (1961) A direct measurement of the radiation sensitivity of normal mouse bone marrow cells.Radiation Res. 14, 213.
Traycoff CM, MR Abboud, J Laver, JE Brandt, R Hoffman, P Law, L Ishizawa, and EF Srour (1994) Evaluation of thein vitro behavior of phenotypically defined populations of umbilical cord blood hematopoietic progenitor cells.Exp. Hematol. 22, 215–222.
Tropepe V, S Hitoshi, C Sirard, TW Mak, J Rossant and D van der Kooy (2001) Direct neural fate specification from embryonic stem cells: a primitive mammalian neural stem cell stage acquired through a default mechanism.Neuron 30(1), 65–78.
Uchida N, DW Buck, D He, MJ Reitsma, M Masek, TV Phan, AS Tsukamoto, FH Gage and IL Weissman (2000) Direct isolation of human central nervous system stem cells.Proc. Natl. Acad. Sci. USA 97, 14720–14725.
Ueno Y, T Miyawaki, H Seki, A Matsuda, K Taga and N Taniguchi (1985) Differential effects of recombinant human interferon-gamma and interleukin 2 on natural killer cell activity of peripheral blood in early human development.J. Immunol. 135, 180–184.
Vaziri H, W Dragowska, RC Allsopp, TE Thomas, CB Harley and PM Lansdorp (1994) Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age.Proc. Natl. Acad. Sci. USA 91(21), 9857–9860.
Wagner JE, HE Broxmeyer, RL Byrd, B Zehnhauer, B Schmeckpeper, N Shah, C Griffin, PD Emanuel, KS Zuckerman, S Cooperet al. (1992) Transplantation of umbilical cord blood after myeloablative therapy: analysis of engraftment.Blood 79, 1874–1881.
Wagner JE, NA Kerman, M Steinbuch, HE Broxmeyer and E Gluckman (1995) Allogeneic sibling umbilical-cord-blood transplantation in children with malignant and non-malignant disease.Lancet 346(8969), 214–219.
Wardrop CA and BM Holland, (1995). Recombinant haemopoietic growth factors in the newborn-will they be useful?Eur. J. Pediatr. 154: S13–14
Willing A, J Lixian, M Milliken, S Poulos, T Zigova, S Song, CD Hart, J Sanchez-Ramos and PR Sanberg (2003) Intavenous versus intrastriatal cor blood administration in a rodent model of stroke.Neurosci. Res. 73(3), 296–307.
Wilson CB, J Westall, L Johnston, DB Lewis, SK Dower and AR Alpert (1986) Decreased production of interferon-gamma by human neonatal cells. Intrinsic and regulatory deficiencies.J. Clin. Invest. 77, 860–867.
Yin AH, S Miraglia, ED Zanjani, G Almeida-Porada, M Ogawa, AG Leary, J Olweus, J Kearney and DW Buck (1997) AC133, a novel marker for human hematopoietic stem and progenitor cells.Blood 90(12), 5002–5012.
Zigova T, S Song, AE Willing, JE Hudson, MB Newman, S Saporta, J Sanchez-Ramos and PR Sanberg (2002) Human umbilical cord blood cells express neural antigens after transplantation into the developing rat brain.Cell Transplant. 11(3), 265–274.
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Newman, M.B., Davis, C.D., Kuzmin-Nichols, N. et al. Human umbilical cord blood (HUCB) cells for central nervous system repair. neurotox res 5, 355–368 (2003). https://doi.org/10.1007/BF03033155
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DOI: https://doi.org/10.1007/BF03033155