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Review

Cord blood as a potential therapeutic for amyotrophic lateral sclerosis

, &
Pages 837-851 | Received 30 Nov 2016, Accepted 24 Apr 2017, Published online: 08 May 2017

References

  • Kiernan MC, Vucic S, Cheah BC, et al. Amyotrophic lateral sclerosis. Lancet. 2011;377:942–955.
  • Sorarù G, Ermani M, Logroscino G, et al. Natural history of upper motor neuron-dominant ALS. Amyotroph Lateral Scler. 2010;11:424–429.
  • Talbot K. Motor neuron disease: the bare essentials. Pract Neurol. 2009;9:303–309.
  • Rosen DR, Siddique T, Patterson D, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993;362:59–62.
  • Gurney ME, Pu H, Chiu AY, et al. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science. 1994;264:1772–1775.
  • Pasinelli P, Brown RH. Molecular biology of amyotrophic lateral sclerosis: insights from genetics. Nat Rev Neurosci. 2006;7:710–723.
  • Taylor JP, Brown RH, Cleveland DW. Decoding ALS: from genes to mechanism. Nature. 2016;539:197–206.
  • Chen S, Sayana P, Zhang X, et al. Genetics of amyotrophic lateral sclerosis: an update. Mol Neurodegener. 2013;8:28.
  • Garbuzova-Davis S, Thomson A, Kurien C, et al. Potential new complication in drug therapy development for amyotrophic lateral sclerosis. Expert Rev Neurother. 2016;16:1397–1405.
  • Rothstein JD. Current hypotheses for the underlying biology of amyotrophic lateral sclerosis. Ann Neurol. 2009;65(Suppl 1):S3–9.
  • Bruijn LI. Amyotrophic lateral sclerosis: from disease mechanisms to therapies. BioTechniques. 2002;32:1112, 1114, 1116 passim.
  • Strong MJ, Kesavapany S, Pant HC. The pathobiology of amyotrophic lateral sclerosis: a proteinopathy? J Neuropathol Exp Neurol. 2005;64:649–664.
  • Wijesekera LC, Leigh PN. Amyotrophic lateral sclerosis. Orphanet J Rare Dis. 2009;4:3.
  • Martin LJ, Price AC, Kaiser A, et al. Mechanisms for neuronal degeneration in amyotrophic lateral sclerosis and in models of motor neuron death (Review). Int J Mol Med. 2000;5:3–13.
  • Rodrigues MCO, Voltarelli JC, Sanberg PR, et al. Immunological aspects in amyotrophic lateral sclerosis. Transl Stroke Res. 2012;3:331–340.
  • Rodrigues MCO, Sanberg PR, Cruz LE, et al. The innate and adaptive immunological aspects in neurodegenerative diseases. J Neuroimmunol. 2014;269:1–8.
  • McCombe PA, Henderson RD. The role of immune and inflammatory mechanisms in ALS. Curr Mol Med. 2011;11:246–254.
  • D’Amico E, Factor-Litvak P, Santella RM, et al. Clinical perspective on oxidative stress in sporadic amyotrophic lateral sclerosis. Free Radic Biol Med. 2013;65:509–527.
  • Papadimitriou D, Le Verche V, Jacquier A, et al. Inflammation in ALS and SMA: sorting out the good from the evil. Neurobiol Dis. 2010;37:493–502.
  • Zhao W, Beers DR, Appel SH. Immune-mediated mechanisms in the pathoprogression of amyotrophic lateral sclerosis. J Neuroimmune Pharmacol. 2013;8:888–899.
  • Yamanaka K, Chun SJ, Boillee S, et al. Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nat Neurosci. 2008;11:251–253.
  • Boillée S, Yamanaka K, Lobsiger CS, et al. Onset and progression in inherited ALS determined by motor neurons and microglia. Science. 2006;312:1389–1392.
  • Appel SH, Smith RG, Engelhardt JI, et al. Evidence for autoimmunity in amyotrophic lateral sclerosis. J Neurol Sci. 1994;124(Suppl):14–19.
  • Garbuzova-Davis S, Haller E, Saporta S, et al. Ultrastructure of blood-brain barrier and blood-spinal cord barrier in SOD1 mice modeling ALS. Brain Res. 2007;1157:126–137.
  • Garbuzova-Davis S, Saporta S, Haller E, et al. Evidence of compromised blood-spinal cord barrier in early and late symptomatic SOD1 mice modeling ALS. PLoS ONE. 2007;2:e1205.
  • Garbuzova-Davis S, Hernandez-Ontiveros DG, Rodrigues MCO, et al. Impaired blood-brain/spinal cord barrier in ALS patients. Brain Res. 2012;1469:114–128.
  • Nicaise C, Mitrecic D, Demetter P, et al. Impaired blood-brain and blood-spinal cord barriers in mutant SOD1-linked ALS rat. Brain Res. 2009;1301:152–162.
  • Zhong Z, Deane R, Ali Z, et al. ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration. Nat Neurosci. 2008;11:420–422.
  • Miyazaki K, Ohta Y, Nagai M, et al. Disruption of neurovascular unit prior to motor neuron degeneration in amyotrophic lateral sclerosis. J Neurosci Res. 2011;89:718–728.
  • Henkel JS, Beers DR, Wen S, et al. Decreased mRNA expression of tight junction proteins in lumbar spinal cords of patients with ALS. Neurology. 2009;72:1614–1616.
  • Winkler EA, Sengillo JD, Sullivan JS, et al. Blood-spinal cord barrier breakdown and pericyte reductions in amyotrophic lateral sclerosis. Acta Neuropathol. 2013;125:111–120.
  • Garbuzova-Davis S, Rodrigues MCO, Hernandez-Ontiveros DG, et al. Amyotrophic lateral sclerosis: a neurovascular disease. Brain Res. 2011;1398:113–125.
  • Garbuzova-Davis S, Saporta S, Sanberg PR. Implications of blood-brain barrier disruption in ALS. Amyotroph Lateral Scler. 2008;9:375–376.
  • Garbuzova-Davis S, Sanberg PR. Blood-CNS barrier impairment in ALS patients versus an animal model. Front Cell Neurosci. 2014;8:21.
  • Yan J, Xu L, Am W, et al. Combined immunosuppressive agents or CD4 antibodies prolong survival of human neural stem cell grafts and improve disease outcomes in amyotrophic lateral sclerosis transgenic mice. Stem Cells. 2006;24:1976–1985.
  • Xu L, Yan J, Chen D, et al. Human neural stem cell grafts ameliorate motor neuron disease in SOD-1 transgenic rats. Transplantation. 2006;82:865–875.
  • Mitrecić D, Nicaise C, Gajović S, et al. differentiation, and survival of intravenously administered neural stem cells in a rat model of amyotrophic lateral sclerosis. Cell Transplant. 2010;19:537–548.
  • Garbuzova-Davis S, Ae W, Milliken M, et al. Intraspinal implantation of hNT neurons into SOD1 mice with apparent motor deficit. Amyotroph Lateral Scler Other Motor Neuron Disord. 2001;2:175–180.
  • Garbuzova-Davis S, Willing AE, Milliken M, et al. Positive effect of transplantation of hNT neurons (NTera 2/D1 cell-line) in a model of familial amyotrophic lateral sclerosis. Exp Neurol. 2002;174:169–180.
  • Garbuzova-Davis S, Willing AE, Saporta S, et al. Multiple transplants of hNT cells into the spinal cord of SOD1 mouse model of familial amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis. 2006;7:221–226.
  • Garbuzova-Davis S, Sanberg PR. Feasibility of cell therapy for amyotrophic lateral sclerosis. Exp Neurol. 2009;216:3–6.
  • Lindvall O, Kokaia Z, Martinez-Serrano A. Stem cell therapy for human neurodegenerative disorders-how to make it work. Nat Med. 2004;10(Suppl):S42–S50.
  • Rizzo F, Riboldi G, Salani S, et al. Cellular therapy to target neuroinflammation in amyotrophic lateral sclerosis. Cell Mol Life Sci. 2014;71:999–1015.
  • Suzuki M, Svendsen CN. Combining growth factor and stem cell therapy for amyotrophic lateral sclerosis. Trends Neurosci. 2008;31:192–198.
  • Lunn JS, Hefferan MP, Marsala M, et al. Stem cells: comprehensive treatments for amyotrophic lateral sclerosis in conjunction with growth factor delivery. Growth Factors. 2009;27:133–140.
  • Haidet-Phillips AM, Maragakis NJ. Neural and glial progenitor transplantation as a neuroprotective strategy for Amyotrophic Lateral Sclerosis (ALS). Brain Res. 2015;1628:343–350.
  • Chen KS, Sakowski SA, Feldman EL. Intraspinal stem cell transplantation for amyotrophic lateral sclerosis. Ann Neurol. 2016;79:342–353.
  • Faravelli I, Riboldi G, Nizzardo M, et al. Stem cell transplantation for amyotrophic lateral sclerosis: therapeutic potential and perspectives on clinical translation. Cell Mol Life Sci. 2014;71:3257–3268.
  • Thomsen GM, Gowing G, Svendsen S, et al. The past, present and future of stem cell clinical trials for ALS. Exp Neurol. 2014;262(Pt B):127–137.
  • Lunn JS, Sakowski SA, Feldman EL. Concise review: Stem cell therapies for amyotrophic lateral sclerosis: recent advances and prospects for the future. Stem Cells. 2014;32:1099–1109.
  • Boulis NM, Federici T, Glass JD, et al. Translational stem cell therapy for amyotrophic lateral sclerosis. Nat Rev Neurol. 2011;8:172–176.
  • Haim ED, Williams SN, Sanberg PR, et al. Recent Patents in Cell Therapy for Amyotrophic Lateral Sclerosis. Recent Patents on Regenerative Medicine. 2015;5:10–19.
  • Sanberg PR, Willing AE, Cahill DW. Novel cellular approaches to repair of neurodegenerative disease: from Sertoli cells to umbilical cord blood stem cells. Neurotox Res. 2002;4:95–101.
  • Sanberg PR, Willing AE, Garbuzova-Davis S, et al. Umbilical cord blood-derived stem cells and brain repair. Ann N Y Acad Sci. 2005;1049:67–83.
  • Sanberg PR, Eve DJ, Willing AE, et al. The treatment of neurodegenerative disorders using umbilical cord blood and menstrual blood-derived stem cells. Cell Transplant. 2011;20:85–94.
  • Garbuzova-Davis S, Willing AE, Saporta S, et al. Novel cell therapy approaches for brain repair. Prog Brain Res. 2006;157:207–222.
  • Low CB, Liou Y-C, Tang BL. Neural differentiation and potential use of stem cells from the human umbilical cord for central nervous system transplantation therapy. J Neurosci Res. 2008;86:1670–1679.
  • McGuckin CP, Forraz N, Baradez M-O, et al. Production of stem cells with embryonic characteristics from human umbilical cord blood. Cell Prolif. 2005;38:245–255.
  • Gluckman E, Rocha V. History of the clinical use of umbilical cord blood hematopoietic cells. Cytotherapy. 2005;7:219–227.
  • Broxmeyer HE. Umbilical cord transplantation: epilogue. Semin Hematol. 2010;47:97–103.
  • Ballen KK, Gluckman E, Broxmeyer HE. Umbilical cord blood transplantation: the first 25 years and beyond. Blood. 2013;122:491–498.
  • Roura S, Pujal J-M, Gálvez-Montón C, et al. The role and potential of umbilical cord blood in an era of new therapies: a review. Stem Cell Res Ther. 2015;6:123.
  • Rocha V, Wagner JE, Sobocinski KA, et al. Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling. Eurocord and International Bone Marrow Transplant Registry Working Committee on Alternative Donor and Stem Cell Sources. N Engl J Med. 2000;342:1846–1854.
  • Rocha V, Cornish J, Sievers EL, et al. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia. Blood. 2001;97:2962–2971.
  • Broxmeyer HE. Primitive hematopoietic stem and progenitor cells in human umbilical cord blood: an alternative source of transplantable cells. Cancer Treat Res. 1996;84:139–148.
  • Cardoso AA, Li ML, Batard P, et al. Human umbilical cord blood CD34+ cell purification with high yield of early progenitors. J Hematother. 1993;2:275–279.
  • Mayani H, Lansdorp PM. Biology of human umbilical cord blood-derived hematopoietic stem/progenitor cells. Stem Cells. 1998;16:153–165.
  • Nayar B, Raju GMK, Deka D. Hematopoietic stem/progenitor cell harvesting from umbilical cord blood. Int J Gynaecol Obstet. 2002;79:31–32.
  • Todaro AM, Pafumi C, Pernicone G, et al. Haematopoietic progenitors from umbilical cord blood. Blood Purif. 2000;18:144–147.
  • Bicknese AR, Goodwin HS, Quinn CO, et al. Human umbilical cord blood cells can be induced to express markers for neurons and glia. Cell Transplant. 2002;11:261–264.
  • Sanchez-Ramos JR, Song S, Kamath SG, et al. Expression of neural markers in human umbilical cord blood. Exp Neurol. 2001;171:109–115.
  • Sanchez-Ramos JR. Neural cells derived from adult bone marrow and umbilical cord blood. J Neurosci Res. 2002;69:880–893.
  • Chen N, Hudson JE, Walczak P, et al. Human umbilical cord blood progenitors: the potential of these hematopoietic cells to become neural. Stem Cells. 2005;23:1560–1570.
  • Zola H, Fusco M, Macardle PJ, et al. Expression of cytokine receptors by human cord blood lymphocytes: comparison with adult blood lymphocytes. Pediatr Res. 1995;38:397–403.
  • Rainsford E, Reen DJ. Interleukin 10, produced in abundance by human newborn T cells, may be the regulator of increased tolerance associated with cord blood stem cell transplantation. Br J Haematol. 2002;116:702–709.
  • Vendrame M, Gemma C, Mesquita DD, et al. Anti-inflammatory Effects of Human Cord Blood Cells in a Rat Model of Stroke. Stem Cells Dev. 2005;14:595–604.
  • Chen J, Sanberg PR, Li Y, et al. Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats. Stroke. 2001;32:2682–2688.
  • Ae W, Lixian J, Milliken M, et al. Intravenous versus intrastriatal cord blood administration in a rodent model of stroke. J Neurosci Res. 2003;73:296–307.
  • Nikolic WV, Hou H, Town T, et al. Peripherally administered human umbilical cord blood cells reduce parenchymal and vascular beta-amyloid deposits in Alzheimer mice. Stem Cells Dev. 2008;17:423–439.
  • Darlington D, Deng J, Giunta B, et al. Multiple low-dose infusions of human umbilical cord blood cells improve cognitive impairments and reduce amyloid-β-associated neuropathology in Alzheimer mice. Stem Cells Dev. 2013;22:412–421.
  • Darlington D, Li S, Hou H, et al. Human umbilical cord blood-derived monocytes improve cognitive deficits and reduce amyloid-β pathology in PSAPP mice. Cell Transplant. 2015;24:2237–2250.
  • Ehrhart J, Darlington D, Kuzmin-Nichols N, et al. Bio-distribution of Infused human umbilical cord blood cells in Alzheimer’s disease-like murine model. Cell Transplant.  2016;25:195–199.
  • Garbuzova-Davis S, Klasko SK, Sanberg PR. Intravenous administration of human umbilical cord blood cells in an animal model of MPS III B. J Comp Neurol. 2009;515:93–101.
  • Garbuzova-Davis S, Willing AE, Desjarlais T, et al. Transplantation of human umbilical cord blood cells benefits an animal model of Sanfilippo syndrome type B. Stem Cells Dev. 2005;14:384–394.
  • Willing AE, Garbuzova-Davis SN, Zayko O, et al. Repeated administrations of human umbilical cord blood cells improve disease outcomes in a mouse model of Sanfilippo syndrome type III B. Cell Transplant. 2014;23:1613–1630.
  • Lu D, Sanberg PR, Mahmood A, et al. Intravenous administration of human umbilical cord blood reduces neurological deficit in the rat after traumatic brain injury. Cell Transplant. 2002;11:275–281.
  • De La Peña I, Sanberg PR, Acosta S, et al. G-CSF as an adjunctive therapy with umbilical cord blood cell transplantation for traumatic brain injury. Cell Transplant. 2015;24:447–457.
  • Saporta S, Kim -J-J, Willing AE, et al. Human umbilical cord blood stem cells infusion in spinal cord injury: engraftment and beneficial influence on behavior. J Hematother Stem Cell Res. 2003;12:271–278.
  • Pranke P, Failace RR, Allebrandt WF, et al. Hematologic and immunophenotypic characterization of human umbilical cord blood. Acta Haematol. 2001;105:71–76.
  • Newcomb JD, Sanberg PR, Klasko SK, et al. Umbilical cord blood research: current and future perspectives. Cell Transplant. 2007;16:151–158.
  • Harris DT, Schumacher MJ, Locascio J, et al. Phenotypic and functional immaturity of human umbilical cord blood T lymphocytes. Proc Natl Acad Sci USA. 1992;89:10006–10010.
  • D’Arena G, Musto P, Cascavilla N, et al. Flow cytometric characterization of human umbilical cord blood lymphocytes: immunophenotypic features. Haematologica. 1998;83:197–203.
  • Han P, Hodge G, Story C, et al. Phenotypic analysis of functional T-lymphocyte subtypes and natural killer cells in human cord blood: relevance to umbilical cord blood transplantation. Br J Haematol. 1995;89:733–740.
  • Saudemont A, Madrigal JA. Immunotherapy after hematopoietic stem cell transplantation using umbilical cord blood-derived products. Cancer Immunol Immunother. 2017;66:215–221.
  • Prabhu SB, Rathore DK, Nair D, et al. Comparison of Human Neonatal and Adult Blood Leukocyte Subset Composition Phenotypes. PLoS ONE. 2016;11:e0162242.
  • Mayani H. Umbilical cord blood: lessons learned and lingering challenges after more than 20 years of basic and clinical research. Arch Med Res. 2011;42:645–651.
  • Wang JC, Doedens M, Dick JE. Primitive human hematopoietic cells are enriched in cord blood compared with adult bone marrow or mobilized peripheral blood as measured by the quantitative in vivo SCID-repopulating cell assay. Blood. 1997;89:3919–3924.
  • Nimgaonkar MT, Roscoe RA, Persichetti J, et al. A unique population of CD34+ cells in cord blood. Stem Cells. 1995;13:158–166.
  • Körbling M, Anderlini P. Peripheral blood stem cell versus bone marrow allotransplantation: does the source of hematopoietic stem cells matter? Blood. 2001;98:2900–2908.
  • Sutherland DR, Keating A, Nayar R, et al. Sensitive detection and enumeration of CD34+ cells in peripheral and cord blood by flow cytometry. Exp Hematol. 1994;22:1003–1010.
  • Erices A, Conget P, Minguell JJ. Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol. 2000;109:235–242.
  • Yang S-E, Ha C-W, Jung M, et al. Mesenchymal stem/progenitor cells developed in cultures from UC blood. Cytotherapy. 2004;6:476–486.
  • Wexler SA, Donaldson C, Denning-Kendall P, et al. Adult bone marrow is a rich source of human mesenchymal “stem” cells but umbilical cord and mobilized adult blood are not. Br J Haematol. 2003;121:368–374.
  • Martins AA, Paiva A, Morgado JM, et al. Quantification and immunophenotypic characterization of bone marrow and umbilical cord blood mesenchymal stem cells by multicolor flow cytometry. Transplant Proc. 2009;41:943–946.
  • Musina RA, Bekchanova ES, Belyavskii AV, et al. Umbilical cord blood mesenchymal stem cells. Bull Exp Biol Med. 2007;143:127–131.
  • Kern S, Eichler H, Stoeve J, et al. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 2006;24:1294–1301.
  • Jin HJ, Bae YK, Kim M, et al. Comparative analysis of human mesenchymal stem cells from bone marrow, adipose tissue, and umbilical cord blood as sources of cell therapy. Int J Mol Sci. 2013;14:17986–18001.
  • Lee MW, Jang IK, Yoo KH, et al. Stem and progenitor cells in human umbilical cord blood. Int J Hematol. 2010;92:45–51.
  • Van De Ven C, Collins D, Bradley MB, et al. The potential of umbilical cord blood multipotent stem cells for nonhematopoietic tissue and cell regeneration. Exp Hematol. 2007;35:1753–1765.
  • McGuckin CP, Forraz N. Potential for access to embryonic-like cells from human umbilical cord blood. Cell Prolif. 2008;41(Suppl 1):31–40.
  • Rogers I, Casper RF. Stem cells: you can’t tell a cell by its cover. Hum Reprod Update. 2003;9:25–33.
  • Rogers I, Casper RF. Umbilical cord blood stem cells. Best Pract Res Clin Obstet Gynaecol. 2004;18:893–908.
  • Matsumoto T, Mugishima H. Non-hematopoietic stem cells in umbilical cord blood. Int J Stem Cells. 2009;2:83–89.
  • Coelho P, Baker B, Chapman J, et al. Stem and Progenitor Cell Compositions Recovered from Bone Marrow or Cord Blood; System and Method for Preparation Thereof. WO/2008/121120, 2008
  • Garbuzova-Davis S, Balber A, Davis-Sanberg C, et al. Treating amyotrophic lateral sclerosis (ALS) with isolated aldehyde dehydrogenase-positive umbilical cord blood cells. US8765119 B2, 2014
  • Ingram DA, Mead LE, Tanaka H, et al. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood. 2004;104:2752–2760.
  • Nieda M, Nicol A, Denning-Kendall P, et al. Endothelial cell precursors are normal components of human umbilical cord blood. Br J Haematol. 1997;98:775–777.
  • Mead LE, Prater D, Yoder MC, et al. Isolation and characterization of endothelial progenitor cells from human blood. Curr Protoc Stem Cell Biol. 2008;Chapter 2:Unit 2C.1.
  • Duan H-X, Cheng L-M, Wang J, et al. Angiogenic potential difference between two types of endothelial progenitor cells from human umbilical cord blood. Cell Biol Int. 2006;30:1018–1027.
  • Broxmeyer HE, Benninger L, Yip-Schneider M, et al. Commentary: a rapid proliferation assay for unknown co-stimulating factors in cord blood plasma possibly involved in enhancement of in vitro expansion and replating capacity of human hematopoietic stem/progenitor cells. Blood Cells. 1994;20:492–497.
  • Kim Y-M, Jung M-H, Song H-Y, et al. Ex vivo expansion of human umbilical cord blood-derived T-lymphocytes with homologous cord blood plasma. Tohoku J Exp Med. 2005;205:115–122.
  • Bojanić I, Golubić Cepulić B. Umbilical cord blood as a source of stem cells. Acta Med Croatica. 2006;60:215–225.
  • Buzanska L, Machaj EK, Zablocka B, et al. Human cord blood-derived cells attain neuronal and glial features in vitro. J Cell Sci. 2002;115:2131–2138.
  • Buzańska L, Jurga M, Domańska-Janik K. Neuronal differentiation of human umbilical cord blood neural stem-like cell line. Neurodegener Dis. 2006;3:19–26.
  • Ha Y, Choi JU, Yoon DH, et al. Neural phenotype expression of cultured human cord blood cells in vitro. Neuroreport. 2001;12:3523–3527.
  • Garbuzova-Davis S, Willing AE, Zigova T, et al. Intravenous administration of human umbilical cord blood cells in a mouse model of amyotrophic lateral sclerosis: distribution, migration, and differentiation. J Hematother Stem Cell Res. 2003;12:255–270.
  • Chen N, Kamath S, Newcomb J, et al. Trophic factor induction of human umbilical cord blood cells in vitro and in vivo. J Neural Eng. 2007;4:130–145.
  • Chen N, Newcomb J, Garbuzova-Davis S, et al. Human Umbilical Cord Blood Cells Have Trophic Effects on Young and Aging Hippocampal Neurons in Vitro. Aging Dis. 2010;1:173–190.
  • Newman MB, Willing AE, Manresa JJ, et al. Cytokines produced by cultured human umbilical cord blood (HUCB) cells: implications for brain repair. Exp Neurol. 2006;199:201–208.
  • Neuhoff S, Moers J, Rieks M, et al. Proliferation, differentiation, and cytokine secretion of human umbilical cord blood-derived mononuclear cells in vitro. Exp Hematol. 2007;35:1119–1131.
  • Fan C-G, Zhang Q-J, Tang F-W, et al. Human umbilical cord blood cells express neurotrophic factors. Neurosci Lett. 2005;380:322–325.
  • Rizvanov AA, Kiyasov AP, Gaziziov IM, et al. Human umbilical cord blood cells transfected with VEGF and L(1)CAM do not differentiate into neurons but transform into vascular endothelial cells and secrete neuro-trophic factors to support neuro-genesis-a novel approach in stem cell therapy. Neurochem Int. 2008;53:389–394.
  • Eggermann J, Kliche S, Jarmy G, et al. Endothelial progenitor cell culture and differentiation in vitro: a methodological comparison using human umbilical cord blood. Cardiovasc Res. 2003;58:478–486.
  • Hristov M, Erl W, Weber PC. Endothelial progenitor cells: mobilization, differentiation, and homing. Arterioscler Thromb Vasc Biol. 2003;23:1185–1189.
  • Broxmeyer HE, Hangoc G, Cooper S, et al. Growth characteristics and expansion of human umbilical cord blood and estimation of its potential for transplantation in adults. Proc Natl Acad Sci USA. 1992;89:4109–4113.
  • Gilmore GL, DePasquale DK, Lister J, et al. Ex vivo expansion of human umbilical cord blood and peripheral blood CD34(+) hematopoietic stem cells. Exp Hematol. 2000;28:1297–1305.
  • Koestenbauer S, Zisch A, Dohr G, et al. Protocols for hematopoietic stem cell expansion from umbilical cord blood. Cell Transplant. 2009;18:1059–1068.
  • Ko K-H, Nordon R, O’Brien TA, et al. Ex Vivo Expansion of Hematopoietic Stem Cells to Improve Engraftment in Stem Cell Transplantation. Methods Mol Biol. 2017;1524:301–311.
  • Ende N, Weinstein F, Chen R, et al. Human umbilical cord blood effect on sod mice (amyotrophic lateral sclerosis). Life Sci. 2000;67:53–59. .
  • Chen R, Ende N. The potential for the use of mononuclear cells from human umbilical cord blood in the treatment of amyotrophic lateral sclerosis in SOD1 mice. J Med. 2000;31:21–30.
  • Garbuzova-Davis S, Sanberg CD, Kuzmin-Nichols N, et al. Human umbilical cord blood treatment in a mouse model of ALS: optimization of cell dose. PLoS ONE. 2008;3:e2494.
  • Garbuzova-Davis S, Rodrigues MCO, Mirtyl S, et al. Multiple intravenous administrations of human umbilical cord blood cells benefit in a mouse model of ALS. PLoS ONE. 2012;7:e31254.
  • Souayah N, Coakley KM, Chen R, et al. Defective neuromuscular transmission in the SOD1 G93A transgenic mouse improves after administration of human umbilical cord blood cells. Stem Cell Rev. 2012;8:224–228.
  • Knippenberg S, Thau N, Schwabe K, et al. Intraspinal injection of human umbilical cord blood-derived cells is neuroprotective in a transgenic mouse model of amyotrophic lateral sclerosis. Neurodegener Dis. 2012;9:107–120.
  • Willenbrock S, Knippenberg S, Meier M, et al. In vivo MRI of intraspinally injected SPIO-labelled human CD34+ cells in a transgenic mouse model of ALS. In Vivo. 2012;26:31–38.
  • Habisch H-J, Janowski M, Binder D, et al. Intrathecal application of neuroectodermally converted stem cells into a mouse model of ALS: limited intraparenchymal migration and survival narrows therapeutic effects. J Neural Transm (Vienna). 2007;114:1395–1406.
  • Bigini P, Veglianese P, Andriolo G, et al. Intracerebroventricular administration of human umbilical cord blood cells delays disease progression in two murine models of motor neuron degeneration. Rejuvenation Res. 2011;14:623–639.
  • Mukhamedyarov MA, Rizvanov AA, Safiullov ZZ, et al. Analysis of the efficiency of gene-cell therapy in transgenic mice with amyotrophic lateral sclerosis phenotype. Bull Exp Biol Med. 2013;154:558–561.
  • Rizvanov AA, Guseva DS, Salafutdinov II, et al. Genetically modified human umbilical cord blood cells expressing vascular endothelial growth factor and fibroblast growth factor 2 differentiate into glial cells after transplantation into amyotrophic lateral sclerosis transgenic mice. Exp Biol Med (Maywood). 2011;236:91–98.
  • Garanina EE, Mukhamedshina YO, Salafutdinov II, et al. Construction of recombinant adenovirus containing picorna-viral 2A-peptide sequence for the co-expression of neuro-protective growth factors in human umbilical cord blood cells. Spinal Cord. 2016;54:423–430.
  • Guseva D, Rizvanov AA, Salafutdinov II, et al. Over-expression of Oct4 and Sox2 transcription factors enhances differentiation of human umbilical cord blood cells in vivo. Biochem Biophys Res Commun. 2014;451:503–509.
  • Islamov RR, Rizvanov AA, Mukhamedyarov MA, et al. Symptomatic improvement, increased life-span and sustained cell homing in amyotrophic lateral sclerosis after transplantation of human umbilical cord blood cells genetically modified with adeno-viral vectors expressing a neuro-protective factor and a neural cell adhesion molecule. Curr Gene Ther. 2015;15:266–276.
  • Islamov RR, Rizvanov AA, Fedotova VY, et al. Tandem Delivery of Multiple Therapeutic Genes Using Umbilical Cord Blood Cells Improves Symptomatic Outcomes in ALS. Mol Neurobiol. 2016.Epub Aug 6.
  • Freireich EJ, Gehan EA, Rall DP, et al. Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey, and man. Cancer Chemother Rep. 1966;50:219–244.
  • Cabanes C, Bonilla S, Tabares L, et al. Neuroprotective effect of adult hematopoietic stem cells in a mouse model of motoneuron degeneration. Neurobiol Dis. 2007;26:408–418.
  • Gubert F, Decotelli AB, Bonacossa-Pereira I, et al. Intraspinal bone-marrow cell therapy at pre- and symptomatic phases in a mouse model of amyotrophic lateral sclerosis. Stem Cell Res Ther. 2016;7:41.
  • Knopf PM, Cserr HF, Nolan SC, et al. Physiology and immunology of lymphatic drainage of interstitial and cerebrospinal fluid from the brain. Neuropathol Appl Neurobiol. 1995;21:175–180.
  • Calias P, Banks WA, Begley D, et al. Intrathecal delivery of protein therapeutics to the brain: a critical reassessment. Pharmacol Ther. 2014;144:114–122.
  • Ehrhart J, Smith AJ, Kuzmin-Nichols N, et al. Humoral factors in ALS patients during disease progression. J Neuroinflammation. 2015;12:127.
  • Teng YD, Yu D, Ropper AE, et al. Functional multipotency of stem cells: a conceptual review of neurotrophic factor-based evidence and its role in translational research. Curr Neuropharmacol. 2011;9:574–585.
  • Deda H, Inci MC, Kürekçi AE, et al. Treatment of amyotrophic lateral sclerosis patients by autologous bone marrow-derived hematopoietic stem cell transplantation: a 1-year follow-up. Cytotherapy. 2009;11:18–25.
  • Kim C, Lee HC, Sung -J-J. Amyotrophic lateral sclerosis - cell based therapy and novel therapeutic development. Exp Neurobiol. 2014;23:207–214.
  • Gelati M, Profico D, Projetti-Pensi M, et al. Culturing and expansion of “clinical grade” precursors cells from the fetal human central nervous system. Methods Mol Biol. 2013;1059:65–77.
  • Mazzini L, Gelati M, Profico DC, et al. Human neural stem cell transplantation in ALS: initial results from a phase I trial. J Transl Med. 2015;13:17.
  • Martinez HR, Gonzalez-Garza MT, Moreno-Cuevas JE, et al. Stem-cell transplantation into the frontal motor cortex in amyotrophic lateral sclerosis patients. Cytotherapy. 2009;11:26–34.

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