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研究生: 簡基城
Chi-Chen Chien
論文名稱: 利用臍血單核球細胞為底之平台方法研究靈芝的免疫調控影響
Studies of Immunomodulation Effect of Ganoderma lucidum Using an in vitro Cord Blood MNC-Based Platform Method
指導教授: 張晃猷
Hwan-You Chung
口試委員:
學位類別: 博士
Doctor
系所名稱: 生命科學暨醫學院 - 生命科學系
Department of Life Sciences
論文出版年: 2004
畢業學年度: 92
語文別: 英文
論文頁數: 102
中文關鍵詞: 幹細胞靈芝葡萄籽自然殺手細胞單核球保健食品臍帶血免疫
外文關鍵詞: Stem cell, NK cell, ADCC, CAM, CD, CTL, DC, E/T ratio, FSC, GSPE, GVHD, hUBC, LAK, LPS, MACS, MHC, MNC, NKT cell, PBMC, PBS, SSC, TCR, antibody-dependent cell-mediated cytotoxicity, complementary and alternative medicine, cluster of differentiation, cytolytic T lymphocyte, dendritic cell, effector to target cell ratio, forward scatter, grape seed proanthocyanidine extract, graft versus host disease, human umbilical cord blood, lymphokine-activated killer cell, lipopolysacharide, magnetic-bead cell separation method, major histocompatibility complex, mononuclear cell, natural killer cell, natural killer/T lymphocyte cell, peripheral mononuclear cell, phosphate buffered saline, side scatter, T cell receptor
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  • 在這個研究裡,我們發展出一個可以測試天然物的in vitro實驗模式。這個模式利用人類臍帶血的單核細胞作為檢測平台,來觀察在細胞培養中加入天然物,經過培養之後,不同的免疫細胞表現型呈現的改變情形。傳統的一些保健天然物,比如靈芝或葡萄子萃取物,以之加入細胞培養中七天,進行觀察並用流式細胞計數法分析。在臍帶血單核細胞之中的幹細胞/祖原細胞,被天然物中的有效成分所誘導,在培養中逐漸進行增生、成熟以及分化的情形。與對照組相比較,許多經過天然物刺激後的細胞表現型呈現的變化,顯示出統計學上有意義的差異。
    流式細胞計數儀器是用來做細胞型表現的分析。在這個研究中,我們也發展出一種以細胞流液壓力式的微晶片,在安捷倫生物分析機 (Bioanalyzer) 上應用,結果證實可以用來替代傳統的流式細胞儀分析,所需要的細胞甚至少到兩百個而已,這對於不容易取得細胞來源而僅有極少量細胞時的實驗將是非常重要。
    利用本平台測試,我們觀察到靈芝可以增加自然殺手細胞在臍帶血單核細胞中的比率。而經過天然物誘導增多後的自然殺手細胞,拿來做細胞毒殺測試,其能力是正常的。同時,這些誘導增加後的免疫細胞,也讓我們用來觀察作用細胞(effector) 與目標細胞之間的較佳毒殺力比率。至於在細胞分化的不同時間做觀察設計,未來也可以用來協助進行系統生物學的研究。
    以這個模式篩選有免疫效力的天然物是十分合用的。我們發現有些天然物可以增加某種免疫細胞比率,相對的有些卻減少免疫細胞數。進而我們又用這一個模型對特定天然物之內的有效組成,分別再加以驗證,以找出究竟是那一部分的化學成分在作用上最要緊。這麼一來,想要針對於具有促進免疫力的天然物全力投入生產或著研究者就可以很快找出方向。
    經由本實驗,我們又確認了天然物在某些濃度以下,刺激免疫細胞增多的效果是不夠的,藉此可以定量出較佳的有效刺激濃度,而有助於測定一些增強免疫力為主之健康食品的有效口服劑量。
    總之,本研究顯示了這個細胞測試平台可以幫助改善保健天然物最常被詬病的科學證據不足的弱點。幹細胞/祖原細胞的確可被許多天然物所刺激及誘導,從而改變其細胞分化以及增殖的軌跡;若再加上其他的分子生物技術,此方法也可以有助於藥物開發的。


    An in vitro model for testing natural substances is developed in this study. The model used mononuclear cells (MNCs) from human umbilical cord blood (hUCB) for phenotypic expression induction platform. Natural substances, such as Ganoderma or grape seed proanthocyanidins extract, were added to the medium and then cultured for seven days. The stem cells/progenitors contained in the mononuclear cells were modulated by the active ingredients and changed in the course of differentiation and maturation. Flow cytometry was used for phenotypic analysis. Meanwhile, we utilized a cell-fluid based microchip on Agilent Bioanalyzer, and discovered an alternative assay method for phenotypic expression studies. Such a measurement could analyze the phenotypes of cells in a small population as few as 200 cells with good sensitivity and accuracy.
    We found that Ganoderma lucidum extract could enhance the NK cells composition in immune cell subpopulation when used to treat hUCB MNCs. After treatment, the enriched NK cells preserved similar cytotoxicity function. Enrichment of specific subsets of immune cells enabled us to explore further studies, such as investigating the optimal effector-to-target cells ratio in this study, or potential future systems biology experiments during differentiation courses.
    The model was also utilized to screen different sort of natural substances. We found that, for example, wheat grass extract up-regulated CD 56+ NK cell composition, whereas rutin and quercetin down-regulated instead. Different fractions of natural substances could be further testified quickly with this platform.
    Furthermore, we observed no significant change as the concentration of natural substance was below a critical concentration. The optimal oral consumption dosage of a specific natural health product could be predicted.
    Taken together, we demonstrated that this technique provides a good platform to study natural substances. The responses of stem cells/progenitors to natural substances, the alteration in phenotypic expression of immune cell subpopulation, and the modulation of human immunity could be further explicated using this technique.

    Abstract …………………………………………………………………………… i Table of contents …………………………………………………………………. v Abbreviation ……………………………………………………………………… vi Chapter I ………………………………………………………………………….. 01 Background and significance Chapter II …………………………………………………………………………. 12 Investigation of Different Natural Products Alternating Phenotypic Expression of Immune Cells in Umbilical Cord Blood Chapter III ………………………………………………………………………... 19 Cell Phenotype Analysis Using a Cell-fluid Based Microchip with High Sensitivity and Accurate Quantitation Chapter IV …………………………………………………………………………31 How the Polysaccharides of Ganoderma lucidum Alter Cell immunophenotypic Expression and Enhance CD56+ NK-Cell Cytotoxicity in Cord blood Chapter V ………………………………………………………………………… 45 Discussion and Conclusion Chapter VI ………………………………………………………………………... 54 Perspectives. Figures and tables …………………………………………………………………59 Reference …………………………………………………………………………. 86

    REFERENCES

    1. Yu LC, Wall DA, Sandler E, Chan KW, Grayson G, Kletzel M. 2001. Unrelated cord blood transplant experience by the pediatric blood and marrow transplant consortium. Pediatr Hematol Oncol. 18:235-245.
    2. Barker JN, Wagner JE. 2002. Umbilical cord blood transplantation: current state of art. Curr Opin Oncol. 14:160-164.
    3. Mugishima H, Takahashi T, Nagamura T, Asano S, Saito H. 2002. Umbilical cord blood for unrelated bone marrow replacement; Asia bank and Japan cord blood bank network update. Int J Hematol. 76 Suppl 2:284-286.
    4. Lee TD. 2002. Marrow donor registry and cord blood bank in Taiwan. Int J Hematol. 76 Suppl 1:312-314
    5. Lam AC, Li K, Zhang XB, Li CK, Fok TF, Chang AM, James AE, Tsang KS, Yuen PM. 2001. Preclinical ex vivo expansion of cord blood hematopoietic stem and progenitor cells: duration of culture; the media, serum supplements, and growth factors used; and engraftment in NOD/SCID mice. Transfusion. 41:1567-1576.
    6. De Bruyn C, Delforge A, Bernier M, Bron D. 2003. Ex vivo expansion of neutrophil precursor cells from fresh and cryopreserved cord blood cells. Cytotherapy. 5:87-98.
    7. Hiramatsu H, Nishikomori R, Heike T, Ito M, Kobayashi K, Katamura K, Nakahata T. 2003. Complete reconstitution of human lymphocytes from cord blood CD34+ cells using the NOD/SCID/gammacnull mice model. Blood. 102:873-880.
    8. Hou L, Cao H, Wang D, Wei G, Bai C, Zhang Y, Pei X. 2003.Induction of umbilical cord blood mesenchymal stem cells into neuron-like cells in vitro. Int J Hematol. 78:256-261.
    9. Shpall EJ, Quinones R, Giller R, Zeng C, Baron AE, Jones RB, Bearman SI, Nieto Y, Freed B, Madinger N, Hogan CJ, Slat-Vasquez V, Russell P, Blunk B, Schissel D, Hild E, Malcolm J, Ward W, McNiece IK. 2002. Transplantation of ex vivo expanded cord blood. Biol Blood Marrow Transplant. 8:368-376.
    10. Ueda T, Yoshida M, Yoshino H, Kobayashi K, Kawahata M, Ebihara Y, Ito M, Asano S, Nakahata T, Tsuji K. 2001. Hematopoietic capability of CD34+ cord blood cells: a comparison with CD34+ adult bone marrow cells. Int J Hematol. 73:457-462.
    11. Carayol G, Robin C, Bourhis JH, Bennaceur-Griscelli A, Chouaib S, Coulombel L, Caignard A. 1998.NK cells differentiated from bone marrow, cord blood and peripheral blood stem cells exhibit similar phenotype and functions. Eur J Immunol. 28:1991-2002.
    12. Perez SA, Sotiropoulou PA, Gkika DG, Mahaira LG, Niarchos DK, Gritzapis AD, Kavalakis YG, Antsaklis AI, Baxevanis CN, Papamichail M. 2003. A novel myeloid-like NK cell progenitor in human umbilical cord blood. Blood. 101:3444-3450.
    13. Trinchieri. G . 1989. Biology of natural killer cells. Adv Imunol. 47:187-376.
    14. Bancroft, G. 1993. The role of natural killer cells in innate resistance to infection. Curr Opin Immunol. 4:503-510.
    15. Carayol G, Robin C, Bourhis JH, Bennaceur-Griscelli A, Chouaib S, Coulombel L, Caignard A. 1998. NK cells differentiated from bone marrow, cord blood and peripheral blood stem cells exhibit similar phenotype and functions. Eur J Immunol. 28:1991-2002.
    16. Gaddy J, Broxmeyer HE. 1997. Cord blood CD16+56- cells with low lytic activity are possible precursors of mature nature killer cells. Cell Immunol 180:132-135.
    17. Ljunggren, H.G., Karre, K. 1990. In search of the “missing self” MHC molecules and K cell recognition. Immunol Today. 11:237-244.
    18. Moretta A, Bottino C, Vitale M, Pende D, Biassoni R, Mingari MC, Moretta L. 1996. Receptors for HLA class-I molecules in human natural killer cells. Annu Rev Immunol. 14: 619-648.
    19. Moretta L., Bottino C., Pende D. 2002. Human natural killer cells: their origin, receptors and function. Eur J Immunol. 32:1205-1211.
    20. Rolstad, B., Seaman, WE. 1998. Natural killer cells and recognition of MHC class I molecules: new perspectives and challenges in immunology.
    Scand J Immunol. 47:412-425.
    21. Hao Q-L, Zhu J, Price MA, at al. 2001. Identification of a novel, human multilymphoid progenitor in cord blood. Blood. 97:3683-3690.
    22. Bennett IM, Zatsepena O, Zamai L. 1996 Definition of a natural killer NKR-P1A+/CD56-/CD16- functionally immature human NK subset that differentiates in vitro in the presence of interleukin 12. J Exp Med. 184:1845-1856.
    23. Chang G, Rondrigues A, Carretero M et al. 1995 Molecular characterization of human CD94: a type II membrane glycoprotein related to the C-type lectin superfamily. Eur J Aimmunol. 25:2433-2437.
    24. Lanier LL, Chang C, Philips JH. 1994. Human NKR-P1A: a disulfide-linked homodimer of the C-type lectin superfamily expressed by a subset of NK and T lymphocytes. J Immunol. 153:2417-2428.
    25. Lanier LL, Le AM, Civin Cl. 1986. The relationship of CD16(Leu-11) and Leu-19(NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes. J Immunol. 136:4480-4486.
    26. Cooper MA, Fehniger TA,Tumer SC, et al. 2001. Human natural killer cells: a unique immuno-regulatory role for the CD56bright subset. Blood. 97:3146-3151.
    27. Wasser SP, Weis AL. 1999. Therapeutic effects of substances occurring in higher Basidiomycetes mushrooms: a modern perspective. Crit Rev Immunol 19:65-96.
    28. Shiao, M. S. 2003. Natural products of the medicinal fungus Ganoderma lucidum: occurrence, biological activities, and pharmacological functions. Chem Rec. 3:172-180.
    29. van der Hem LG, van der Vliet JA, Bocken CF, Kino K, Hoitsma AJ, Tax WJ. 1995. Ling Zhi-8: studies of a new immunomodulating agent. Transplantation. 60:438-443.
    30. Kino K, Yamashita A, Yamaoka K, Watanabe J, Tanaka S, Ko K, Shimizu K, Tsunoo H. 1989. Isolation and characterization of a new immunomodulatory protein, ling zhi-8 (LZ-8), from Ganoderma lucidium. J Biol Chem. 264:472-478.
    31. Tanaka S, Ko K, Kino K, Tsuchiya K, Yamashita A, Murasugi A, Sakuma S, Tsunoo H. 1989. Complete amino acid sequence of an immunomodulatory protein, ling zhi-8 (LZ-8). An immunomodulator from a fungus, Ganoderma lucidium, having similarity to immunoglobulin variable regions. J Biol Chem. 264:16372-16377.
    32. Wang, S-Y, Hsu, M-L, Hsu, H-C, Tzeng, C-H, Lee S-S, Shiao, M-S and Ho C-K. 1997. The anti-tumor effect of Ganoderma lucidum is mediated by cytokines released from activated macrophages and T lymphocytes. International Journal Of Cancer. 70: 699-705.
    33. Zhang, J., Wang, G., Li, H., Zhuang, C., Mizuno, T., Ito, H., Mayuzumi, H., Okamoto, H., Li, J. 1994. Antitumor active protein-containing glycans from the Chinese mushroom songshan lingzhi, Ganoderma tsugae mycelium. Bioscience Biotechnology and Biochemistry. 58: 1202-1205.
    34. Lee, S.Y. and Rhee, H. M. 1990. Cardiovascular effects of mycelium extract of Ganoderma lucidum: inhibition of sympathetic outflow as a mechanism of its hypotensive action. Chemical and Pharmaceutical Bulletin. 38: 1359-1364.
    35. Kabir, Y., Kimura, S. and Tamura, T. (1998) Dietary effect of Ganoderma lucidum mushroom on blood pressure and lipid levels in spontaneously hypertensive rats (SHR). Journal of Nutritional Science and Vitaminology. 43: 433-438.
    36. Lien, E.-J. 1990. Progress in Drug Research. Birkhauser: Basel, Vol. 34, p 395.
    37. Tao, J. and Feng, K. Y. 1990. Experimental and clinical studies on inhibitory effect of Ganoderma lucidum on platelet aggregation. Journal of Tongji Medical University. 10: 240-243.
    38. Shimizu, A., Yano, T., Saito,Y. and Inada, Y. 1985. Isolation of an inhibitor of platelet aggregation from a fungus, Ganoderma lucidum. Chemical and Pharmaceutical Bulletin. 33: 3012-3015.
    39. Hijikata Y, Yamada S. 1998. Effect of Ganoderma lucidum on postherpetic neuralgia. Am J Chin Med. 26:375-381.
    40. El-Mekkawy, S., Meselhy, M. R., Nakamura, N., Tezuka, Y., Hattori, M., Kakiuchi, N., Shimotohno, K., Kawahata, T. and Otake, T. 1998. Anti-HIV-1 and anti-HIV-1-protease substances from Ganoderma lucidum.
    Phytochemistry. 49:1651-1657.
    41. B4 Min BS, Nakamura N, Miyashiro H, Bae KW, Hattori M. 1998. Triterpenes from the spores of Ganoderma lucidum and their inhibitory activity against HIV-1 protease. Chem Pharm Bull. 46:1607-1612.
    42. Lin LJ, Shiao MS. 1987. Separation of oxygenated triterpenoids from Ganoderma lucidum by high-performance liquid chromatography. J Chromatogr. 410:195-200.
    43. Wang SY, Hsu ML, Hsu HC, Tzeng CH, Lee SS, Shiao MS, Ho CK. 1997. The anti-tumor effect of Ganoderma lucidum is mediated by cytokines released from activated macrophages and T lymphocytes. Int J Cancer. 70:699-705.
    44. Muller A, Rice PJ, Ensley HE, Coogan PS, Kalbfleish JH, Kelley JL, Love EJ, Portera CA, Ha T, Browder IW, Williams DL. 1996. Receptor binding and internalization of a water-soluble (1-->3)-beta-D-glucan biologic response modifier in two monocyte/macrophage cell lines. J Immunol. 156:3418-3425.
    45. Wang, Y. Y., K. H. Khoo, S. T. Chen, C. C. Lin, C. H. Wong, and C. H. Lin. 2002. Studies on the immuno-modulating and antitumor activities of Ganoderma lucidum (Reishi) polysaccharides: functional and proteomic analyses of a fucose-containing glycoprotein fraction responsible for the activities. Bioorg Med Chem. 10:1057-1062.
    46. Murota K, Terao J. 2003. Antioxidative flavonoid quercetin: implication of its intestinal absorption and metabolism. Murota K, Terao J. Arch Biochem Biophys. 417:12-17.
    47. Alcocer F, Whitley D, Salazar-Gonzalez JF, Jordan WD, Sellers MT, Eckhoff DE, Suzuki K, Macrae C, Bland KI. 2002. Quercetin inhibits human vascular smooth muscle cell proliferation and migration. Surgery. 131:198-204.
    48. Kim SS, Oh OJ, Min HY, Park EJ, Kim Y, Park HJ, Nam Han Y, Lee SK. 2003. Eugenol suppresses cyclooxygenase-2 expression in lipopolysaccharide-stimulated mouse macrophage RAW264.7 cells. Life Sci. 73:337-348.
    49. Capasso R, Pinto L, Vuotto ML, Di Carlo G. 2000. Preventive effect of eugenol on PAF and ethanol-induced gastric mucosal damage. Fitoterapia. 71 Suppl 1:131-137.
    50. Yamakoshi J, Kataoka S, Koga T, Ariga T. 2002. Proanthocyanidin-rich extract from grape seeds attenuates the development of aortic atherosclerosis in cholesterol-fed rabbits. Hypertens Res. 25:99-107.
    51. Natella F, Belelli F, Gentili V, Ursini F, Scaccini C. 2002. Grape seed proanthocyanidins prevent plasma postprandial oxidative stress in humans. J Agric Food Chem. 50:7720-7725.
    52. Matteucci E, Rizvi SI, Giampietro O. 2001. Erythrocyte sodium/hydrogen exchange inhibition by (-) epicatechin. Cell Biol Int. 25:771-776.
    53. Arts IC, Jacobs DR Jr, Gross M, Harnack LJ, Folsom AR. 2002. Dietary catechins and cancer incidence among postmenopausal women: the Iowa Women's Health Study (United States). Cancer Causes Control. 13:373-82.
    54. T. Horsburgh, S. Martin, A.J. Robson. 2000. The application of flow cytometry to histocompatibility testing. Transpl Immunol. 8:3-15. Review.
    55. C.H. Liu, W.L. Ma, R. Shi, Q. Ouyang, W.L. Zheng. 2002. Application of Agilent Bioanalyzer in the study of differential gene expression. Di Yi Jun Yi Da Xue Xue Bao. 12: 1066.
    56. R. Ohashi, J.M. Otero, A. Chwistek, J.F. Hamel. 2002. Determination of monoclonal antibody production in cell culture using novel microfluidic and traditional assays. Electropho. 20: 3623-9.
    57. O.Schmut, J. Horwath-Winter, A. Zenker, G. Trummer, Graefes Arch. 2002. The effect of sample treatment on separation profiles of tear fluid proteins: qualitative and semi-quantitative protein determination by an automated analysis system. Clin Exp Ophthalmol. 240:900-905.
    58. Hows JM. Status of umbilical cord blood transplantation in the year 2001. J Clin Pathol. 54:428-433.
    59. E. Marshall. 1996. Clinical promise, ethical quandary. Science. 271:586-8.
    60. J. Jaroscak, K. Goltry, A. Smith, B.Waters-Pick, P.L. Martin, T. Driscoll, R. Howrey, N. Chao, J. Douville, S. Burhop, P. Fu, J. Kurtzberg. 2003. Augmentation of umbilical cord blood (UCB) transplantation with ex vivo-expanded UCB cells: results of a phase 1 trial using the AastromReplicell System. Blood. 101:5061-5067.
    61. Davis MM. 1990. T cell receptor gene diversity and selection. Annu Rev Biochem. 59:475-496. Review.
    62. T.F. Tedder, J. Tuscano, S. Sato, J.H. Kehrl. 1997. CD22, a B lymphocyte-specific adhesion molecule that regulates antigen receptor signaling.
    Annu Rev Immunol. 15:481-504. Review.
    63. Carter, R. H., Y. Wang, and S. Brooks. 2002. Role of CD19 signal transduction in B cell biology. Immunol Res. 26:45-49.
    64. J. Pugin, I.D. Heumann, A. Tomasz, V.V. Kravchenko, Y. Akamatsu, M. Nishijima, M.P. Glauser, P.S. Tobias, R.J. Ulevitch. 1994. Immunity. 1:509-516.
    65. R. Majeti, Z. Xu, T.G. Parslow, J.L. Olson, D.I. Daikh, N. Killeen, A. Weiss. 2000. An inactivating point mutation in the inhibitory wedge of CD45 causes lymphoproliferation and autoimmunity. Cell. 103:1059-1070.
    66. Y. Jin, L. Fuller, M. Carreno, V. Esquenazi, A.G. Tzakis, J. Miller. 1998. The regulation of phenotype and function of human liver CD3+/CD56+ lymphocytes, and cells that also co-express CD8 by IL-2, IL-12 and anti-CD3 monoclonal antibody. Hum Immunol. 59:352-362.
    67. L.J. Zhou and T.F. Tedder. 1995. A distinct pattern of cytokine gene expression by human CD83+ blood dendritic cells. Blood. 86:3295-3301.
    68. Wang, K.H. Khoo, S.T. Chen, C.H. Wong, and C. H. Lin. 2002. Studies on the immuno-modulating and antitumor activities of Ganoderma lucidum (Reishi) polysaccharides: functional and proteomic analyses of a fucose-containing glycoprotein fraction responsible for the activities. Bioorg Med Chem. 10:1057-1062.
    69. P. Decherchi, P. Cochard, P. Gauthier. 1997. Dual staining assessment of Schwann cell viability within whole peripheral nerves using calcein-AM and ethidium homodimer. J Neurosci Methods. 71:205-213.
    70. Becton Dickinson Immunocytometry Systems
    71. D'Arena G, Musto P, Cascavilla N, Di Giorgio G, Fusilli S, Zendoli F, Carotenuto M. 1998. Flow cytometric characterization of human umbilical cord blood lymphocytes: immunophenotypic features. Haematologica. 83:197-203.
    72. C. Rabian-Herzog, S. Lesage, E. Gluckman. 1992. Characterization of lymphocyte subpopulations in cord blood. Bone Marrow Transplant. Suppl. 1:64-67.
    73. D. Motley, M. P. Meyer, R. A. King, G. J, Naus.1996. Determination of lymphocyte immunophenotypic values for normal full-term cord blood. Am J Clin Pathol. 105:38-43.
    74. Wasser, S. P., and A. L. Weis. 1999. Therapeutic effects of substances occurring in higher Basidiomycetes mushrooms: a modern perspective. Crit Rev Immunol. 19:65-96. Review.
    75. Lien, E. J. 1990. Fungal metabolites and Chinese herbal medicine as immunostimulants. Prog Drug Res. 34:395-420.
    76. Zhang, J., G. Wang, H. Li, C. Zhuang, T. Mizuno, H. Ito, H. Mayuzumi, H. Okamoto, and J. Li. 1994. Antitumor active protein-containing glycans from the Chinese mushroom songshan lingzhi, Ganoderma tsugae mycelium. Biosci Biotechnol Biochem 58:1202-1205.
    77. Carter, R. H., Y. Wang, and S. Brooks. 2002. Role of CD19 signal transduction in B cell biology. Immunol Res. 26:45-54. Review.
    78. Foley, R., R. Tozer, and Y. Wan. 2001. Genetically modified dendritic cells in cancer therapy: implications for transfusion medicine. Transfus Med Rev. 15:292-304. Review.
    79. Schantz, S. P., B. W. Brown, E. Lira, D. L. Taylor, and N. Beddingfield. 1987. Evidence for the role of natural immunity in the control of metastatic spread of head and neck cancer. Cancer Immunol Immunother 25:141-148.
    80. Cooper, M. A., T. A. Fehniger, and M. A. Caligiuri. 2001. The biology of human natural killer-cell subsets. Trends Immunol. 22:633-640. Review.
    81. Wang, S. Y., M. L. Hsu, H. C. Hsu, C. H. Tzeng, S. S. Lee, M. S. Shiao, and C. K. Ho. 1997. The anti-tumor effect of Ganoderma lucidum is mediated by cytokines released from activated macrophages and T lymphocytes. Int J Cancer 70:699-705.
    82. Joshi, S. S., N. N. Babushkina-Patz, D. J. Verbik, T. G. Gross, S. R. Tarantolo, C. A. Kuszynski, S. J. Pirruccello, M. R. Bishop, and A. Kessinger. 1998. Antitumor activity of human umbilical cord blood cells: A comparative analysis with peripheral blood and bone marrow cells. Int J Oncol 13:791-779.
    83. Schantz, S. P., B. W. Brown, E. Lira, D. L. Taylor, and N. Beddingfield. 1987. Evidence for the role of natural immunity in the control of metastatic spread of head and neck cancer. Cancer Immunol Immunother. 25:141-148.
    84. Wasser, S. P., and A. L. Weis. 1999. Therapeutic effects of substances occurring in higher Basidiomycetes mushrooms: a modern perspective. Crit Rev Immunol. 19:65-96. Review.
    85. Colucci, F., M. A. Caligiuri, and J. P. Di Santo. 2003. What does it take to make a natural killer? Nat Rev Immunol. 3:413-425. Review.
    86. Warren, H. S., F. T. Christiansen, and C. S. Witt. 2003. Functional inhibitory human leucocyte antigen class I receptors on natural killer (NK) cells in patients with chronic NK lymphocytosis. Br J Haematol. 121:793-804.
    87. Won, S. J., M. T. Lin, and W. L. Wu. 1992. Ganoderma tsugae mycelium enhances splenic natural killer cell activity and serum interferon production in mice. Jpn J Pharmacol. 59:171-176.
    88. Nociari, M. M., A. Shalev, P. Benias, and C. Russo. 1998. A novel one-step, highly sensitive fluorometric assay to evaluate cell-mediated cytotoxicity. J Immunol Methods. 213:157-167.
    89. Joshi, S. S., N. N. Babushkina-Patz, D. J. Verbik, T. G. Gross, S. R. Tarantolo, C. A. Kuszynski, S. J. Pirruccello, M. R. Bishop, and A. Kessinger. 1998. Antitumor activity of human umbilical cord blood cells: A comparative analysis with peripheral blood and bone marrow cells. Int J Oncol. 13:791-799.
    90. Roehm, N. W., G. H. Rodgers, S. M. Hatfield, and A. L. Glasebrook. 1991. An improved colorimetric assay for cell proliferation and viability utilizing the tetrazolium salt XTT. J Immunol Methods. 142:257-265.
    91. Scudiero, D. A., R. H. Shoemaker, K. D. Paull, A. Monks, S. Tierney, T. H. Nofziger, M. J. Currens, D. Seniff, and M. R. Boyd. 1988. Evaluation of a soluble tetrazolium/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines. Cancer Res. 48:4827-4833.
    92. Gritzapis, A. D., D. Dimitroulopoulos, E. Paraskevas, C. N. Baxevanis, and M. Papamichail. 2002. Large-scale expansion of CD3(+)CD56(+) lymphocytes capable of lysing autologous tumor cells with cytokine-rich supernatants. Cancer Immunol Immunother. 51:440-448.
    93. Barron V, Lyons E, Stenson-Cox C, McHugh PE, Pandit A. 2003. Bioreactors for cardiovascular cell and tissue growth: a review. Ann Biomed Eng. 31:1017-1030.
    94. Gerlach JC, Mutig K, Sauer IM, Schrade P, Efimova E, Mieder T, Naumann G, Grunwald A, Pless G, Mas A, Bachmann S, Neuhaus P, Zeilinger K. 2003. Use of primary human liver cells originating from discarded grafts in a bioreactor for liver support therapy and the prospects of culturing adult liver stem cells in bioreactors: a morphologic study. Transplantation. 76:781-786.
    95. Ginis I, Luo Y, Miura T, Thies S, Brandenberger R, Gerecht-Nir S, Amit M, Hoke A, Carpenter MK, Itskovitz-Eldor J, Rao MS. 2004. Differences between human and mouse embryonic stem cells. Dev Biol. 269:360-380.
    96. Shachar M, Cohen S. 2003. Cardiac tissue engineering, ex-vivo: design principles in biomaterials and bioreactors. Heart Fail Rev. 8:271-276.
    97. Grow AE, Wood LL, Claycomb JL, Thompson PA. 2003. New biochip technology for label-free detection of pathogens and their toxins. J Microbiol Methods. 53:221-233.
    98. Wagner JE, Verfaillie CM. 2004. Ex vivo expansion of umbilical cord blood hemopoietic stem and progenitor cells. Exp Hematol. 32:412-413.
    99. Porter VR, Greendale GA, Schocken M, Zhu X, Effros RB. 2001. Immune effects of hormone replacement therapy in post-menopausal women. Exp Gerontol. 36:311-326.
    100. Smith JA, Bluestone JA. 1997. T cell inactivation and cytokine deviation promoted by anti-CD3 mAbs. Curr Opin Immunol. 9:648-654.
    101. Burns EA, Leventhal EA.2001. Aging, immunity, and cancer. Cancer Control. 8:288-290.
    102. Heydarkhan-Hagvall S, Helenius G, Johansson BR, Li JY, Mattsson E, Risberg B. 2003. Co-culture of endothelial cells and smooth muscle cells affects gene expression of angiogenic factors. J Cell Biochem. 89:1250-1259.

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