Human umbilical cord blood cell grafts for brain ischemia

Cell Transplantation

Volumn 18, Issue 9, 2009, Pages 985-998

  Park, Dong Hyuk ^a,b   Borlongan, Cesar V ^a   Willing, Alison E ^a   Eve, David J ^a   Cruz, L Eduardo ^c   Sanberg, Cyndy D ^d   Chung, Yong Gu ^b   Sanberg, Paul R ^a,e  

^a UNIVERSITY OF SOUTH FLORIDA   (United States)

^b Korea University Ansan Hospital   (South Korea)

^c Cryopraxis and Silvestre Laboratory   (Brazil)

^d Saneron CCEL Therapeutics Inc   (United States)

^e UNIVERSITY OF SOUTH FLORIDA   (United States)

Author keywords

Angiogenesis; Human umbilical cord blood cells; Inflammation; Middle cerebral artery occlusion; Neurogenesis; Stroke; Transplantation

Indexed keywords

GROWTH FACTOR; MEMBRANE ANTIGEN; NEUROTROPHIC FACTOR;

ANGIOGENESIS; ANTIINFLAMMATORY ACTIVITY; BLOOD CELL; BRAIN; BRAIN BLOOD FLOW; BRAIN ISCHEMIA; CELL COMPOSITION; CELL LINEAGE; CELL PROLIFERATION; CELL SURVIVAL; CELL THERAPY; CONFERENCE PAPER; HEMATOPOIETIC STEM CELL; HUMAN; IMMUNOMODULATION; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; MONONUCLEAR CELL; NERVE CELL DIFFERENTIATION; NEUROLOGIC DISEASE; NONHUMAN; PRIORITY JOURNAL; STROKE; STROKE PATIENT; UMBILICAL CORD BLOOD;

ANIMALS; BRAIN ISCHEMIA; CELL DIFFERENTIATION; CORD BLOOD STEM CELL TRANSPLANTATION; DISEASE MODELS, ANIMAL; FETAL BLOOD; HUMANS; MODELS, BIOLOGICAL; NEOVASCULARIZATION, PHYSIOLOGIC; NEUROGENESIS;

EID: 74049103054     PISSN: 09636897     EISSN: None     Source Type: Journal    
DOI: 10.3727/096368909X471279     Document Type: Conference Paper

References (139)

1. Alvarez-Mercado, A. I.; Saez-Lara, M. J.; Garcia-Mediavilla, M. V.; Sanchez-Campos, S.; Abadia, F.; Cabello-Donayre, M.; Gil, A.; Gonzalez-Gallego, J.; Fontana, L. Xenotransplantation of human umbilical cord blood mononuclear cells to rats with D-galactosamine-induced hepatitis. Cell Transplant. 17(7):845-857; 2008.
2. Arien-Zakay, H.; Lecht, S.; Bercu, M. M.; Tabakman, R.; Kohen, R.; Galski, H.; Nagler, A.; Lazarovici, P. Neuroprotection by cord blood neural progenitors involves antioxidants, neurotrophic and angiogenic factors. Exp. Neurol. 216(1):83-94; 2009.
3. Armitage, J. O. Bone marrow transplantation. N. Engl. J. Med. 330(12):827-838; 1994.
4. Arpinati, M.; Green, C. L.; Heimfeld, S.; Heuser, J. E.; Anasetti, C. Granulocyte-colony stimulating factor mobilizes T helper 2-inducing dendritic cells. Blood 95(8):2484-2490; 2000.
5. Asseman, C.; Powrie, F. Interleukin 10 is a growth factor for a population of regulatory T cells. Gut 42(2):157-158; 1998.
6. Babcock, A. A.; Kuziel, W. A.; Rivest, S.; Owens, T. Chemokine expression by glial cells directs leukocytes to sites of axonal injury in the CNS. J. Neurosci. 23(21):7922-7930; 2003.
7. Berger, M. J.; Adams, S. D.; Tigges, B. M.; Sprague, S. L.; Wang, X. J.; Collins, D. P.; McKenna, D. H. Differentiation of umbilical cord blood-derived multilineage progenitor cells into respiratory epithelial cells. Cytotherapy 8(5):480-487; 2006.
8. Bicknese, A. R.; Goodwin, H. S.; Quinn, C. O.; Henderson, V. C.; Chien, S. N.; Wall, D. A. Human umbilical cord blood cells can be induced to express markers for neurons and glia. Cell Transplant. 11(3):261-264; 2002.
9. Bjornson, C. R.; Rietze, R. L.; Reynolds, B. A.; Magli, M. C.; Vescovi, A. L. Turning brain into blood: A hematopoietic fate adopted by adult neural stem cells in vivo. Science 283(5401):534-537; 1999.
10. Borlongan, C. V.; Hadman, M.; Sanberg, C. D.; Sanberg, P. R. Central nervous system entry of peripherally in jected umbilical cord blood cells is not required for neuroprotection in stroke. Stroke 35(10):2385-2389; 2004.
11. Broxmeyer, H. E.; Hangoc, G.; Cooper, S.; Ribeiro, R. C.; Graves, V.; Yoder, M.; Wagner, J.; Vadhan-Raj, S.; Benninger, L.; Rubinstein, P.; 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 89(9):4109-4113; 1992.
12. Buelens, C.; Willems, F.; Delvaux, A.; Pierard, G.; Delville, J. P.; Velu, T.; Goldman, M. Interleukin-10 differentially regulates B7-1 (CD80) and B7-2 (CD86) expression on human peripheral blood dendritic cells. Eur. J. Immunol. 25(9):2668-2672; 1995.
13. Buzanska, L.; Machaj, E. K.; Zablocka, B.; Pojda, Z.; Domanska-Janik, K. Human cord blood-derived cells attain neuronal and glial features in vitro. J. Cell Sci. 115(Pt. 10):2131-2138; 2002.
14. Cardoso, A. A.; Li, M. L.; Batard, P.; Hatzfeld, A.; Brown, E. L.; Levesque, J. P.; Sookdeo, H.; Panterne, B.; Sansilvestri, P.; Clark, S. C.; et al. 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; 1993.
15. Chang, Y. C.; Shyu, W. C.; Lin, S. Z.; Li, H. Regenerative therapy for stroke. Cell Transplant. 16(2):171-181; 2007.
16. Chen, J.; Li, Y.; Wang, L.; Zhang, Z.; Lu, D.; Lu, M.; Chopp, M. Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 32(4):1005-1011; 2001.
17. Chen, J.; Sanberg, P. R.; Li, Y.; Wang, L.; Lu, M.; Willing, A. E.; Sanchez-Ramos, J.; Chopp, M. Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats. Stroke 32(11):2682-2688; 2001.
18. Chen, J.; Zhang, Z. G.; Li, Y.; Wang, L.; Xu, Y. X.; Gautam, S. C.; Lu, M.; Zhu, Z.; Chopp, M. Intravenous administration of human bone marrow stromal cells induces angiogenesis in the ischemic boundary zone after stroke in rats. Circ. Res. 92(6):692-699; 2003.
19. Chen, N.; Hudson, J. E.; Walczak, P.; Misiuta, I.; Garbuzova-Davis, S.; Jiang, L.; Sanchez-Ramos, J.; Sanberg, P. R.; Zigova, T.; Willing, A. E. Human umbilical cord blood progenitors: The potential of these hematopoietic cells to become neural. Stem Cells 23(10):1560-1570; 2005.
20. Chen, N.; Kamath, S.; Newcomb, J.; Hudson, J.; Garbuzova-Davis, S.; Bickford, P.; Davis-Sanberg, C.; Sanberg, P.; Zigova, T.; Willing, A. Trophic factor induction of human umbilical cord blood cells in vitro and in vivo. J. Neural Eng. 4(2):130-145; 2007.
21. Chen, S. H.; Chang, F. M.; Tsai, Y. C.; Huang, K. F.; Lin, C. L.; Lin, M. T. Infusion of human umbilical cord blood cells protect against cerebral ischemia and damage during heatstroke in the rat. Exp. Neurol. 199(1):67-76; 2006.
22. Chen, X.; Li, Y.; Wang, L.; Katakowski, M.; Zhang, L.; Chen, J.; Xu, Y.; Gautam, S. C.; Chopp, M. Ischemic rat brain extracts induce human marrow stromal cell growth factor production. Neuropathology 22(4):275-279; 2002.
23. Chivu, M.; Diaconu, C. C.; Bleotu, C.; Alexiu, I.; Brasoveanu, L.; Cernescu, C. The comparison of different protocols for expansion of umbilical-cord blood hematopoietic stem cells. J. Cell. Mol. Med. 8(2):223-231; 2004.
24. Clemens, J. A. Cerebral ischemia: gene activation, neuronal injury, and the protective role of antioxidants. Free Radic. Biol. Med. 28(10):1526-1531; 2000.
25. Conrad, P. D.; Emerson, S. G. Ex vivo expansion of hematopoietic cells from umbilical cord blood for clinical transplantation. J. Leukoc. Biol. 64(2):147-155; 1998.
26. Cui, X.; Chen, J.; Zacharek, A.; Roberts, C.; Savant-Bhonsale, S.; Chopp, M. Treatment of stroke with (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate and bone marrow stromal cells upregulates angiopoietin-1/Tie2 and enhances neovascularization. Neuroscience 156(1):155-164; 2008.
27. Daar, A. S.; Bhatt, A.; Court, E.; Singer, P. A. Stem cell research and transplantation: Science leading ethics. Transplant. Proc. 36(8):2504-2506; 2004.
28. Dalle, J. H.; Menezes, J.; Wagner, E.; Blagdon, M.; Champagne, J.; Champagne, M. A.; Duval, M. Characterization of cord blood natural killer cells: Implications for transplantation and neonatal infections. Pediatr. Res. 57(5 Pt. 1):649-655; 2005.
29. D'Arena, G.; Musto, P.; Cascavilla, N.; Di Giorgio, G.; Fusilli, S.; Zendoli, F.; Carotenuto, M. Flow cytometric characterization of human umbilical cord blood lymphocytes: Immunophenotypic features. Haematologica 83(3):197-203; 1998.
30. Ding, D. C.; Shyu, W. C.; Chiang, M. F.; Lin, S. Z.; Chang, Y. C.; Wang, H. J.; Su, C. Y.; Li, H. Enhancement of neuroplasticity through upregulation of beta1-integrin in human umbilical cord-derived stromal cell implanted stroke model. Neurobiol. Dis. 27(3):339-353; 2007.
31. Ding, D. C.; Shyu, W. C.; Lin, S. Z.; Li, H. The role of endothelial progenitor cells in ischemic cerebral and heart diseases. Cell Transplant. 16(3):273-284; 2007.
32. El-Badri, N. S.; Hakki, A.; Saporta, S.; Liang, X.; Madhusodanan, S.; Willing, A. E.; Sanberg, C. D.; Sanberg, P. R. Cord blood mesenchymal stem cells: Potential use in neurological disorders. Stem Cells Dev. 15(4):497-506; 2006.
33. El Marsafy, S.; Dosquet, C.; Coudert, M. C.; Bensussan, A.; Carosella, E.; Gluckman, E. Study of cord blood natural killer cell suppressor activity. Eur. J. Haematol. 66(4):215-220; 2001.
34. Emerich, D. F.; Dean, 3rd, R. L.; Bartus, R. T. The role of leukocytes following cerebral ischemia: pathogenic variable or bystander reaction to emerging infarct? Exp. Neurol. 173(1):168-181; 2002.
35. Erices, A.; Conget, P.; Minguell, J. J. Mesenchymal progenitor cells in human umbilical cord blood. Br. J. Haematol. 109(1):235-242; 2000.
36. Ferrari, G.; Cusella-De Angelis, G.; Coletta, M.; Paolucci, E.; Stornaiuolo, A.; Cossu, G.; Mavilio, F. Muscle regeneration by bone marrow-derived myogenic progenitors. Science 279(5356):1528-1530; 1998.
37. Frassoni, F.; Podesta, M.; Maccario, R.; Giorgiani, G.; Rossi, G.; Zecca, M.; Bacigalupo, A.; Piaggio, G.; Locatelli, F. Cord blood transplantation provides better reconstitution of hematopoietic reservoir compared with bone marrow transplantation. Blood 102(3):1138-1141; 2003.
38. Galli, R.; Borello, U.; Gritti, A.; Minasi, M. G.; Bjornson, C.; Coletta, M.; Mora, M.; De Angelis, M. G.; Fiocco, R.; Cossu, G.; Vescovi, A. L. Skeletal myogenic potential of human and mouse neural stem cells. Nat. Neurosci. 3(10):986-991; 2000.
39. Garbuzova-Davis, S.; Willing, A. E.; Saporta, S.; Bickford, P. C.; Gemma, C.; Chen, N.; Sanberg, C. D.; Klasko, S. K.; Borlongan, C. V.; Sanberg, P. R. Novel cell therapy approaches for brain repair. Prog. Brain Res. 157:207-222; 2006.
40. Garbuzova-Davis, S.; Willing, A. E.; Zigova, T.; Saporta, S.; Justen, E. B.; Lane, J. C.; Hudson, J. E.; Chen, N.; Davis, C. D.; Sanberg, P. R. 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. 12(3):255-270; 2003.
41. Garcia, J. H.; Liu, K. F.; Yoshida, Y.; Lian, J.; Chen, S.; del Zoppo, G. J. Influx of leukocytes and platelets in an evolving brain infarct (Wistar rat). Am. J. Pathol. 144(1):188-199; 1994.
42. Garderet, L.; Dulphy, N.; Douay, C.; Chalumeau, N.; Schaeffer, V.; Zilber, M. T.; Lim, A.; Even, J.; Mooney, N.; Gelin, C.; Gluckman, E.; Charron, D.; Toubert, A. The umbilical cord blood alphabeta T-cell repertoire: characteristics of a polyclonal and naive but completely formed repertoire. Blood 91(1):340-346; 1998.
43. Glabinski, A. R.; Tuohy, V. K.; Ransohoff, R. M. Expression of chemokines RANTES, MIP-1alpha and GRO-alpha correlates with inflammation in acute experimental autoimmune encephalomyelitis. Neuroimmunomodulation 5(3-4):166-171; 1998.
44. Gluckman, E.; Broxmeyer, H. A.; Auerbach, A. D.; Friedman, H. S.; Douglas, G. W.; Devergie, A.; Esperou, H.; Thierry, D.; Socie, G.; Lehn, P.; et al. 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; 1989.
45. Gluckman, E.; Rocha, V. History of the clinical use of umbilical cord blood hematopoietic cells. Cytotherapy 7(3):219-227; 2005.
46. Goodwin, H. S.; Bicknese, A. R.; Chien, S. N.; Bogucki, B. D.; Quinn, C. O.; Wall, D. A. Multilineage differentiation activity by cells isolated from umbilical cord blood: Expression of bone, fat, and neural markers. Biol. Blood Marrow Transplant. 7(11):581-588; 2001.
47. Ha, Y.; Choi, J. U.; Yoon, D. H.; Yeon, D. S.; Lee, J. J.; Kim, H. O.; Cho, Y. E. Neural phenotype expression of cultured human cord blood cells in vitro. Neuroreport 12(16):3523-3527; 2001.
48. Hao, S. G.; Sun, G. L.; Wu, W. L.; Wu, Y. L. [Studies on the dynamics of biological characteristics of CD133+ cells from human umbilical cord blood during short-term culture]. Zhongguo Shi Yan Xue Ye Xue Za Zhi 11(6):569-575; 2003.
49. Harris, D. T.; Schumacher, M. J.; Locascio, J.; Besencon, F. J.; Olson, G. B.; DeLuca, D.; Shenker, L.; Bard, J.; Boyse, E. A. Phenotypic and functional immaturity of human umbilical cord blood T lymphocytes. Proc. Natl. Acad. Sci. USA 89(21):10006-10010; 1992.
50. Henon, P. R. Human embryonic or adult stem cells: an overview on ethics and perspectives for tissue engineering. Adv. Exp. Med. Biol. 534:27-45; 2003.
51. Hirose, Y.; Kiyoi, H.; Itoh, K.; Kato, K.; Saito, H.; Naoe, T. B-cell precursors differentiated from cord blood CD34+ cells are more immature than those derived from granulocyte colony-stimulating factor-mobilized peripheral blood CD34+ cells. Immunology 104(4):410-417; 2001.
52. Hows, J. M.; Bradley, B. A.; Marsh, J. C.; Luft, T.; Coutinho, L.; Testa, N. G.; Dexter, T. M. Growth of human umbilical-cord blood in longterm haemopoietic cultures. Lancet 340(8811):73-76; 1992.
53. Hu, C. H.; Wu, G. F.; Wang, X. Q.; Yang, Y. H.; Du, Z. M.; He, X. H.; Xiang, P. Transplanted human umbilical cord blood mononuclear cells improve left ventricular function through angiogenesis in myocardial infarction. Chin. Med. J. (Engl.) 119(18):1499-1506; 2006.
54. Huang, G. P.; Pan, Z. J.; Jia, B. B.; Zheng, Q.; Xie, C. G.; Gu, J. H.; McNiece, I. K.; Wang, J. F. Ex vivo expansion and transplantation of hematopoietic stem/progenitor cells supported by mesenchymal stem cells from human umbilical cord blood. Cell Transplant. 16(6):579-585; 2007.
55. Jang, J. H.; Kim, S. K.; Choi, J. E.; Kim, Y. J.; Lee, H. W.; Kang, S. Y.; Park, J. S.; Choi, J. H.; Lim, H. Y.; Kim, H. C. Endothelial progenitor cell differentiation using cryopreserved, umbilical cord blood-derived mononuclear cells. Acta Pharmacol. Sin. 28(3):367-374; 2007.
56. Jaroscak, J.; Goltry, K.; Smith, A.; Waters-Pick, B.; Martin, P. L.; Driscoll, T. A.; Howrey, R.; Chao, N.; Douville, J.; Burhop, S.; Fu, P.; Kurtzberg, J. Augmentation of umbilical cord blood (UCB) transplantation with ex vivoexpanded UCB cells: Results of a phase 1 trial using the AastromReplicell System. Blood 101(12):5061-5067; 2003.
57. Jeong, J. A.; Gang, E. J.; Hong, S. H.; Hwang, S. H.; Kim, S. W.; Yang, I. H.; Ahn, C.; Han, H.; Kim, H. Rapid neural differentiation of human cord blood-derived mesenchymal stem cells. Neuroreport 15(11):1731-1734; 2004.
58. Jiang, L.; Newman, M.; Saporta, S.; Chen, N.; Sanberg, C.; Sanberg, P. R.; Willing, A. E. MIP-1alpha and MCP-1 induce migration of human umbilical cord blood cells in models of stroke. Curr. Neurovasc. Res. 5(2):118-124; 2008.
59. Jiang, Q.; Azuma, E.; Hirayama, M.; Iwamoto, S.; Kumamoto, T.; Kobayashi, M.; Yamamoto, H.; Sakurai, M.; Komada, Y. Functional immaturity of cord blood monocytes as detected by impaired response to hepatocyte growth factor. Pediatr. Int. 43(4):334-339; 2001.
60. Jurga, M.; Markiewicz, I.; Sarnowska, A.; Habich, A.; Kozlowska, H.; Lukomska, B.; Buzanska, L.; Domanska-Janik, K. Neurogenic potential of human umbilical cord blood: Neural-like stem cells depend on previous long-term culture conditions. J. Neurosci. Res. 83(4):627-637; 2006.
61. Kernan, N. A.; Bartsch, G.; Ash, R. C.; Beatty, P. G.; Champlin, R.; Filipovich, A.; Gajewski, J.; Hansen, J. A.; Henslee-Downey, J.; McCullough, J.; et al. Analysis of 462 transplantations from unrelated donors facilitated by the National Marrow Donor Program. N. Engl. J. Med. 328(9):593-602; 1993.
62. Kim, B. O.; Tian, H.; Prasongsukarn, K.; Wu, J.; Angoulvant, D.; Wnendt, S.; Muhs, A.; Spitkovsky, D.; Li, R. K. Cell transplantation improves ventricular function after a myocardial infarction: A preclinical study of human unrestricted somatic stem cells in a porcine model. Circulation 112(9 Suppl.):I96-104; 2005.
63. Kim, J. W.; Kim, S. Y.; Park, S. Y.; Kim, Y. M.; Kim, J. M.; Lee, M. H.; Ryu, H. M. Mesenchymal progenitor cells in the human umbilical cord. Ann. Hematol. 83(12):733-738; 2004.
64. Knutsen, A. P.; Wall, D. A. Kinetics of T-cell development of umbilical cord blood transplantation in severe T-cell immunodeficiency disorders. J. Allergy Clin. Immunol. 103(5 Pt. 1):823-832; 1999.
65. Kobari, L.; Giarratana, M. C.; Pflumio, F.; Izac, B.; Coulombel, L.; Douay, L. CD133+ cell selection is an alternative to CD34+ cell selection for ex vivo expansion of hematopoietic stem cells. J. Hematother. Stem Cell Res. 10(2):273-281; 2001.
66. Kosmacheva, S. M.; Volk, M. V.; Yeustratenka, T. A.; Severin, I. N.; Potapnev, M. P. In vitro growth of human umbilical blood mesenchymal stem cells and their differentiation into chondrocytes and osteoblasts. Bull. Exp. Biol. Med. 145(1):141-145; 2008.
67. Krupinski, J.; Kaluza, J.; Kumar, P.; Kumar, S.; Wang, J. M. Role of angiogenesis in patients with cerebral ischemic stroke. Stroke 25(9):1794-1798; 1994.
68. Ladeby, R.; Wirenfeldt, M.; Garcia-Ovejero, D.; Fenger, C.; Dissing-Olesen, L.; Dalmau, I.; Finsen, B. Microglial cell population dynamics in the injured adult central nervous system. Brain Res. Brain Res. Rev. 48(2):196-206; 2005.
69. Laughlin, M. J.; Barker, J.; Bambach, B.; Koc, O. N.; Rizzieri, D. A.; Wagner, J. E.; Gerson, S. L.; Lazarus, H. M.; Cairo, M.; Stevens, C. E.; Rubinstein, P.; Kurtzberg, J. Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors. N. Engl. J. Med. 344(24):1815-1822; 2001.
70. Lee, K. D.; Kuo, T. K.; Whang-Peng, J.; Chung, Y. F.; Lin, C. T.; Chou, S. H.; Chen, J. R.; Chen, Y. P.; Lee, O. K. In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology 40(6):1275-1284; 2004.
71. Liao, S. L.; Chen, W. Y.; Raung, S. L.; Kuo, J. S.; Chen, C. J. Association of immune responses and ischemic brain infarction in rat. Neuroreport 12(9):1943-1947; 2001.
72. Liesveld, J. L. When what you have is not enough: Optimizing cord blood transplantation in adults. Leuk. Res. 27(3):197-199; 2003.
73. Liu, Y.; Liu, T.; Fan, X.; Ma, X.; Cui, Z. Ex vivo expansion of hematopoietic stem cells derived from umbilical cord blood in rotating wall vessel. J. Biotechnol. 124(3):592-601; 2006.
74. Ma, Y.; Zou, P.; Xiao, J.; Huang, S. [The expression and functional characteristics of AC133 antigen in cord blood hematopoietic cells]. Zhonghua Nei Ke Za Zhi 41(12):798-800; 2002.
75. Marler, J. R.; Goldstein, L. B. Medicine. Stroke - tPA and the clinic. Science 301(5640):1677; 2003.
76. McGuckin, C. P.; Forraz, N.; Allouard, Q.; Pettengell, R. Umbilical cord blood stem cells can expand hematopoietic and neuroglial progenitors in vitro. Exp. Cell Res. 295(2):350-359; 2004.
77. Mikami, T.; Eguchi, M.; Kurosawa, H.; Sato, Y.; Sugita, K.; Suzumura, H.; Tadokoro, N.; Watanabe, H.; Inaba, N. Ultrastructural and cytochemical characterization of human cord blood cells. Med. Electron Microsc. 35(2):96-101; 2002.
78. Nakahata, T.; Ogawa, M. Hemopoietic colony-forming cells in umbilical cord blood with extensive capability to generate mono- and multipotential hemopoietic progenitors. J. Clin. Invest. 70(6):1324-1328; 1982.
79. Nayar, B.; Raju, G. M.; Deka, D. Hematopoietic stem/progenitor cell harvesting from umbilical cord blood. Int. J. Gynaecol. Obstet. 79(1):31-32; 2002.
80. Newcomb, J. D.; Ajmo, Jr., C. T.; Sanberg, C. D.; Sanberg, P. R.; Pennypacker, K. R.; Willing, A. E. Timing of cord blood treatment after experimental stroke determines therapeutic efficacy. Cell Transplant. 15(3):213-223; 2006.
81. Newcomb, J. D.; Sanberg, P. R.; Klasko, S. K.; Willing, A. E. Umbilical cord blood research: current and future perspectives. Cell Transplant. 16(2):151-158; 2007.
82. Newman, M. B.; Willing, A. E.; Manresa, J. J.; Davis-Sanberg, C.; Sanberg, P. R. Stroke-induced migration of human umbilical cord blood cells: Time course and cytokines. Stem Cells Dev. 14(5):576-586; 2005.
83. Newman, M. B.; Willing, A. E.; Manresa, J. J.; Sanberg, C. D.; Sanberg, P. R. Cytokines produced by cultured human umbilical cord blood (HUCB) cells: Implications for brain repair. Exp. Neurol. 199(1):201-208; 2006.
84. NINDS. Tissue plasminogen activator for acute ischemic stroke. N. Engl. J. Med. 333(24):1581-1587; 1995.
85. Pesce, M.; Orlandi, A.; Iachininoto, M. G.; Straino, S.; Torella, A. R.; Rizzuti, V.; Pompilio, G.; Bonanno, G.; Scambia, G.; Capogrossi, M. C. Myoendothelial differentiation of human umbilical cord blood-derived stem cells in ischemic limb tissues. Circ. Res. 93(5):e51-62; 2003.
86. Petersen, B. E.; Bowen, W. C.; Patrene, K. D.; Mars, W. M.; Sullivan, A. K.; Murase, N.; Boggs, S. S.; Greenberger, J. S.; Goff, J. P. Bone marrow as a potential source of hepatic oval cells. Science 284(5417):1168-1170; 1999.
87. Pranke, P.; Failace, R. R.; Allebrandt, W. F.; Steibel, G.; Schmidt, F.; Nardi, N. B. Hematologic and immunophenotypic characterization of human umbilical cord blood. Acta Haematol. 105(2):71-76; 2001.
88. Qu, R.; Li, Y.; Gao, Q.; Shen, L.; Zhang, J.; Liu, Z.; Chen, X.; Chopp, M. Neurotrophic and growth factor gene expression profiling of mouse bone marrow stromal cells induced by ischemic brain extracts. Neuropathology 27(4):355-363; 2007.
89. Rainsford, E.; Reen, D. J. 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. 116(3):702-709; 2002.
90. Ramsay, N. K.; Davies, S.; Wagner, J.; McGough, E.; McGlave, P. B. Bone marrow transplantation. New strategies for treating malignant disease. Minn. Med. 79(4):23-28; 1996.
91. Riaz, S. S.; Jauniaux, E.; Stern, G. M.; Bradford, H. F. The controlled conversion of human neural progenitor cells derived from foetal ventral mesencephalon into dopaminergic neurons in vitro. Brain Res. Dev. Brain Res. 136(1):27-34; 2002.
92. Rizvanov, A. A.; Kiyasov, A. P.; Gaziziov, I. M.; Yilmaz, T. S.; Kaligin, M. S.; Andreeva, D. I.; Shafigullina, A. K.; Guseva, D. S.; Kiselev, S. L.; Matin, K.; Palotas, A.; Islamov, R. R. 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. 53(6-8):389-394; 2008.
93. Robinson, S.; Niu, T.; de Lima, M.; Ng, J.; Yang, H.; McMannis, J.; Karandish, S.; Sadeghi, T.; Fu, P.; del Angel, M.; O'Connor, S.; Champlin, R.; Shpall, E. Ex vivo expansion of umbilical cord blood. Cytotherapy 7(3):243-250; 2005.
94. Rocha, V.; Cornish, J.; Sievers, E. L.; Filipovich, A.; Locatelli, F.; Peters, C.; Remberger, M.; Michel, G.; Arcese, W.; Dallorso, S.; Tiedemann, K.; Busca, A.; Chan, K. W.; Kato, S.; Ortega, J.; Vowels, M.; Zander, A.; Souillet, G.; Oakill, A.; Woolfrey, A.; Pay, A. L.; Green, A.; Garnier, F.; Ionescu, I.; Wernet, P.; Sirchia, G.; Rubinstein, P.; Chevret, S.; Gluckman, E. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia. Blood 97(10):2962-2971; 2001.
95. Rocha, V.; Wagner, Jr., J. E.; Sobocinski, K. A.; Klein, J. P.; Zhang, M. J.; Horowitz, M. M.; Gluckman, E. 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. 342(25):1846-1854; 2000.
96. Rosamond, W.; Flegal, K.; Furie, K.; Go, A.; Greenlund, K.; Haase, N.; Hailpern, S. M.; Ho, M.; Howard, V.; Kissela, B.; Kittner, S.; Lloyd-Jones, D.; McDermott, M.; Meigs, J.; Moy, C.; Nichol, G.; O'Donnell, C.; Roger, V.; Sorlie, P.; Steinberger, J.; Thom, T.; Wilson, M.; Hong, Y. Heart disease and stroke statistics - 2008 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 117(4):e25-146; 2008.
97. Sanchez-Ramos, J.; Song, S.; Cardozo-Pelaez, F.; Hazzi, C.; Stedeford, T.; Willing, A.; Freeman, T. B.; Saporta, S.; Janssen, W.; Patel, N.; Cooper, D. R.; Sanberg, P. R. Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp. Neurol. 164(2):247-256; 2000.
98. Sanchez-Ramos, J. R.; Song, S.; Kamath, S. G.; Zigova, T.; Willing, A.; Cardozo-Pelaez, F.; Stedeford, T.; Chopp, M.; Sanberg, P. R. Expression of neural markers in human umbilical cord blood. Exp. Neurol. 171(1):109-115; 2001.
99. Sathananthan, A. H.; Trounson, A. Human embryonic stem cells and their spontaneous differentiation. Ital. J. Anat. Embryol. 110(2 Suppl. 1):151-157; 2005.
100. Shen, L. H.; Li, Y.; Chen, J.; Zhang, J.; Vanguri, P.; Borneman, J.; Chopp, M. Intracarotid transplantation of bone marrow stromal cells increases axon-myelin remodeling after stroke. Neuroscience 137(2):393-399; 2006.
101. Shen, L. H.; Li, Y.; Gao, Q.; Savant-Bhonsale, S.; Chopp, M. Down-regulation of neurocan expression in reactive astrocytes promotes axonal regeneration and facilitates the neurorestorative effects of bone marrow stromal cells in the ischemic rat brain. Glia 56(16):1747-1754; 2008.
102. Shih, C. C.; DiGiusto, D.; Forman, S. J. Ex vivo expansion of transplantable human hematopoietic stem cells: Where do we stand in the year 2000? J. Hematother. Stem Cell Res. 9(5):621-628; 2000.
103. Shirvaikar, N.; Reca, R.; Jalili, A.; Marquez-Curtis, L.; Lee, S. F.; Ratajczak, M. Z.; Janowska-Wieczorek, A. CFU-megakaryocytic progenitors expanded ex vivo from cord blood maintain their in vitro homing potential and express matrix metalloproteinases. Cytotherapy 10(2):182-192; 2008.
104. Shyu, W. C.; Lin, S. Z.; Chiang, M. F.; Su, C. Y.; Li, H. Intracerebral peripheral blood stem cell (CD34+) implantation induces neuroplasticity by enhancing beta1 integrin-mediated angiogenesis in chronic stroke rats. J. Neurosci. 26(13):3444-3453; 2006.
105. Sirchia, G.; Rebulla, P. Placental/umbilical cord blood transplantation. Haematologica 84(8):738-747; 1999.
106. Slusher, B. S.; Vornov, J. J.; Thomas, A. G.; Hurn, P. D.; Harukuni, I.; Bhardwaj, A.; Traystman, R. J.; Robinson, M. B.; Britton, P.; Lu, X. C.; Tortella, F. C.; Wozniak, K. M.; Yudkoff, M.; Potter, B. M.; Jackson, P. F. Selective inhibition of NAALADase, which converts NAAG to glutamate, reduces ischemic brain injury. Nat. Med. 5(12):1396-1402; 1999.
107. Streit, W. J.; Walter, S. A.; Pennell, N. A. Reactive microgliosis. Prog. Neurobiol. 57(6):563-581; 1999.
108. Sunderkotter, C.; Steinbrink, K.; Goebeler, M.; Bhardwaj, R.; Sorg, C. Macrophages and angiogenesis. J. Leukoc. Biol. 55(3):410-422; 1994.
109. Taguchi, A.; Soma, T.; Tanaka, H.; Kanda, T.; Nishimura, H.; Yoshikawa, H.; Tsukamoto, Y.; Iso, H.; Fujimori, Y.; Stern, D. M.; Naritomi, H.; Matsuyama, T. Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. J. Clin. Invest. 114(3):330-338; 2004.
110. Tamaki, S.; Eckert, K.; He, D.; Sutton, R.; Doshe, M.; Jain, G.; Tushinski, R.; Reitsma, M.; Harris, B.; Tsukamoto, A.; Gage, F.; Weissman, I.; Uchida, N. Engraftment of sorted/expanded human central nervous system stem cells from fetal brain. J. Neurosci. Res. 69(6):976-986; 2002.
111. Tan, J.; Town, T.; Paris, D.; Mori, T.; Suo, Z.; Crawford, F.; Mattson, M. P.; Flavell, R. A.; Mullan, M. Microglial activation resulting from CD40-CD40L interaction after beta-amyloid stimulation. Science 286(5448):2352-2355; 1999.
112. Teng, H.; Zhang, Z. G.; Wang, L.; Zhang, R. L.; Zhang, L.; Morris, D.; Gregg, S. R.; Wu, Z.; Jiang, A.; Lu, M.; Zlokovic, B. V.; Chopp, M. Coupling of angiogenesis and neurogenesis in cultured endothelial cells and neural progenitor cells after stroke. J. Cereb. Blood Flow Metab. 28(4):764-771; 2008.
113. Theilgaard-Monch, K.; Raaschou-Jensen, K.; Palm, H.; Schjodt, K.; Heilmann, C.; Vindelov, L.; Jacobsen, N.; Dickmeiss, E. Flow cytometric assessment of lymphocyte subsets, lymphoid progenitors, and hematopoietic stem cells in allogeneic stem cell grafts. Bone Marrow Transplant. 28(11):1073-1082; 2001.
114. Thomson, B. G.; Robertson, K. A.; Gowan, D.; Heilman, D.; Broxmeyer, H. E.; Emanuel, D.; Kotylo, P.; Brahmi, Z.; Smith, F. O. Analysis of engraftment, graft-versus-host disease, and immune recovery following unrelated donor cord blood transplantation. Blood 96(8):2703-2711; 2000.
115. Todaro, A. M.; Pafumi, C.; Pernicone, G.; Munda, S.; Pilastro, M. R.; Russo, A.; Farina, M.; Messina, A. Haematopoietic progenitors from umbilical cord blood. Blood Purif. 18(2):144-147; 2000.
116. Traycoff, C. M.; Abboud, M. R.; Laver, J.; Clapp, D. W.; Srour, E. F. Rapid exit from G0/G1 phases of cell cycle in response to stem cell factor confers on umbilical cord blood CD34+ cells an enhanced ex vivo expansion potential. Exp. Hematol. 22(13):1264-1272; 1994.
117. Traycoff, C. M.; Kosak, S. T.; Grigsby, S.; Srour, E. F. Evaluation of ex vivo expansion potential of cord blood and bone marrow hematopoietic progenitor cells using cell tracking and limiting dilution analysis. Blood 85(8):2059-2068; 1995.
118. Tse, W.; Laughlin, M. J. Umbilical cord blood transplantation: A new alternative option. Hematology 377-383; 2005.
119. Uchida, N.; Buck, D. W.; He, D.; Reitsma, M. J.; Masek, M.; Phan, T. V.; Tsukamoto, A. S.; Gage, F. H.; Weissman, I. L. Direct isolation of human central nervous system stem cells. Proc. Natl. Acad. Sci. USA 97(26):14720-14725; 2000.
120. Vaziri, H.; Dragowska, W.; Allsopp, R. C.; Thomas, T. E.; Harley, C. B.; Lansdorp, P. M. 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; 1994.
121. Vendrame, M.; Cassady, J.; Newcomb, J.; Butler, T.; Pennypacker, K. R.; Zigova, T.; Sanberg, C. D.; Sanberg, P. R.; Willing, A. E. Infusion of human umbilical cord blood cells in a rat model of stroke dose-dependently rescues behavioral deficits and reduces infarct volume. Stroke 35(10):2390-2395; 2004.
122. Vendrame, M.; Gemma, C.; de Mesquita, D.; Collier, L.; Bickford, P. C.; Sanberg, C. D.; Sanberg, P. R.; Pennypacker, K. R.; Willing, A. E. Anti-inflammatory effects of human cord blood cells in a rat model of stroke. Stem Cells Dev. 14(5):595-604; 2005.
123. Vendrame, M.; Gemma, C.; Pennypacker, K. R.; Bickford, P. C.; Davis Sanberg, C.; Sanberg, P. R.; Willing, A. E. Cord blood rescues stroke-induced changes in splenocyte phenotype and function. Exp. Neurol. 199(1):191-200; 2006.
124. Wagner, J. E.; Broxmeyer, H. E.; Byrd, R. L.; Zehnbauer, B.; Schmeckpeper, B.; Shah, N.; Griffin, C.; Emanuel, P. D.; Zuckerman, K. S.; Cooper, S.; et al. Transplantation of umbilical cord blood after myeloablative therapy: Analysis of engraftment. Blood 79(7):1874-1881; 1992.
125. Walczak, P.; Chen, N.; Eve, D.; Hudson, J.; Zigova, T.; Sanchez-Ramos, J.; Sanberg, P. R.; Sanberg, C. D.; Willing, A. E. Long-term cultured human umbilical cord neural-like cells transplanted into the striatum of NOD SCID mice. Brain Res. Bull. 74(1-3):155-163; 2007.
126. Walczak, P.; Chen, N.; Hudson, J. E.; Willing, A. E.; Garbuzova-Davis, S. N.; Song, S.; Sanberg, P. R.; Sanchez-Ramos, J.; Bickford, P. C.; Zigova, T. Do hematopoietic cells exposed to a neurogenic environment mimic properties of endogenous neural precursors? J. Neurosci. Res. 76(2):244-254; 2004.
127. Wei, Y.; Huang, Y.; Zhang, Y.; Zhou, H.; Cao, Q.; Meng, Q.; Lan, J.; Chen, L. Ex vivo expansion of CD34(+) and T and NK cells from umbilical cord blood for leukemic BALB/C nude mouse transplantation. Int. J. Hematol. 87(2):217-224; 2008.
128. Willing, A. E.; Eve, D. J.; Sanberg, P. R. Umbilical cord blood transfusions for prevention of progressive brain injury and induction of neural recovery: An immunological perspective. Regen. Med. 2(4):457-464; 2007.
129. Willing, A. E.; Lixian, J.; Milliken, M.; Poulos, S.; Zigova, T.; Song, S.; Hart, C.; Sanchez-Ramos, J.; Sanberg, P. R. Intravenous versus intrastriatal cord blood administration in a rodent model of stroke. J. Neurosci. Res. 73(3):296-307; 2003.
130. Willing, A. E.; Vendrame, M.; Mallery, J.; Cassady, C. J.; Davis, C. D.; Sanchez-Ramos, J.; Sanberg, P. R. Mobilized peripheral blood cells administered intravenously produce functional recovery in stroke. Cell Transplant. 12(4):449-454; 2003.
131. Womble, T. A.; Green, S.; Sanberg, P. R.; Pennypacker, K. R.; Willing, A. E. CD14+ human umbilical cord blood cells are essential for neurological recovery following MCAO. Cell Transplant. 17(4):485-486; 2008.
132. Xiao, J.; Nan, Z.; Motooka, Y.; Low, W. C. Transplantation of a novel cell line population of umbilical cord blood stem cells ameliorates neurological deficits associated with ischemic brain injury. Stem Cells Dev. 14(6):722-733; 2005.
133. Yang, S. E.; Ha, C. W.; Jung, M.; Jin, H. J.; Lee, M.; Song, H.; Choi, S.; Oh, W.; Yang, Y. S. Mesenchymal stem/progenitor cells developed in cultures from UC blood. Cytotherapy 6(5):476-486; 2004.
134. Yao, C. L.; Feng, Y. H.; Lin, X. Z.; Chu, I. M.; Hsieh, T. B.; Hwang, S. M. Characterization of serum-free ex vivo-expanded hematopoietic stem cells derived from human umbilical cord blood CD133(+) cells. Stem Cells Dev. 15(1):70-78; 2006.
135. Yin, A. H.; Miraglia, S.; Zanjani, E. D.; Almeida-Porada, G.; Ogawa, M.; Leary, A. G.; Olweus, J.; Kearney, J.; Buck, D. W. AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 90(12):5002-5012; 1997.
136. Zhang, J.; Li, Y.; Chen, J.; Yang, M.; Katakowski, M.; Lu, M.; Chopp, M. Expression of insulin-like growth factor 1 and receptor in ischemic rats treated with human marrow stromal cells. Brain Res. 1030(1):19-27; 2004.
137. Zhang, R. L.; Chopp, M.; Chen, H.; Garcia, J. H. Temporal profile of ischemic tissue damage, neutrophil response, and vascular plugging following permanent and transient (2H) middle cerebral artery occlusion in the rat. J. Neurol. Sci. 125(1):3-10; 1994.
138. Zigova, T.; Song, S.; Willing, A. E.; Hudson, J. E.; Newman, M. B.; Saporta, S.; Sanchez-Ramos, J.; Sanberg, P. R. Human umbilical cord blood cells express neural antigens after transplantation into the developing rat brain. Cell Transplant. 11(3):265-274; 2002.
139. Zola, H.; Fusco, M.; Macardle, P. J.; Flego, L.; Roberton, D. Expression