8.1. Abstract
The in vitro response of early haematopoietic progenitors or stem cells (CD34+) — common for myeloid (granulocyte, eosinophil, megakaryocyte) and marrow stromal cell lineages, to neopterin, exogenously added to the liquid mouse bone marrow cultures, at doses 12.5–25 µg/ml culture medium, has been studied. The results obtained show a significant stimulation of common — myeloid and stromal/mesenchymal progenitor cell proliferation and differentiation, as early as 24h to the 96h after the in vitro treatment with neopterin. On day 4 of cultivation the granulocyte/macrophageal proliferation and differentiation has been attenuated giving place to the marrow stromal/mesenchymal cell growth and differentiation. A functional role of neopterin as hematopoietic growth factor — essential for the proliferation and differentiation of bone marrow common (hematopoietic and stromal) progenitors is not yet clear and remains to be elucidated. The in vitro and ex vivo applying of neopterin — alone or in specific combinations with other cytokines (e.g. FGF-2) for the induction of marrow stromal/mesenchymal cell proliferation and differentiation, merits further investigations with regards to its future use in regenerative medicine. The results provide a theoretical basis for the application of neopterin in tissue-engineered devices: incorporated into biodegradable polymer microparticles (with encapsulated early bone marrow progenitors and other special supplements), it could be experimentally applied for fast and easy induction of endothelial, osteoblastic/osteogenic, neuronal and other cell lineage differentiation as well as for improving tissue trophical processes and reparative microenvironment.
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8.8. References
S. Aizawa, M. Hiramoto, S. Araki, H. Hoshi, S. Kojima, K. Wakasugi, In vivo stimulatory effects of neopterin on hematopoiesis, Pteridines 9, 13–17 (1998).
S. Aizawa, M. Hiramoto, S. Araki, S. Negishi, Y. Kimura, H. Hoshi, S. Kojima, K. Wakasugi, Stimulatory effects of neopterin on hematopoiesis in vitro are mediated by activation of stromal cell function, Hematol Oncol 16(2), 57–67 (1998).
F. Barry, J. Murphy, K. English, B. Mahon, Immunogenicity of adult mesenchymal stem cells: lessons from the fetal allograft, Stem Cells Dev 14(3), 252–265 (2005).
J. Chen, S. Sotome, J. Wang, H. Orii, T. Uemura, K. Shinomiya, Correlation of in vivo bone formation capability and in vitro differentiation of human bone marrow stromal cells, J Med Dent Sci 52(1), 27–34 (2005).
H. Egusa, F. Schweizer, C. Wang, Y. Matsuka, I. Nishimura, Neuronal differentiation of bone marrow-derived stromal stem cells involves suppression of discordant phenotypes through gene silencing, J Biol Chem 280(25), 23691–23697 (2005).
B. Frick, K. Schroecksnadel, G. Neurauter, F. Leblhuber and D. Fuchs, Increasing production of homocysteine and neopterin and degradation of tryptophan with older age, Clin Biochem 37(8), 684–687(2004).
S. Hankemeier, M. Keus, J. Zeichen, M. Jagodzinski, T. Barkhausen, U. Bosch, C. Krettek, M. Van Griensven, Modulation of proliferation and differentiation of human bone marrow stromal cells by fibroblast growth factor 2: potential implications for tissue engineering of tendons and ligaments, Tissue Eng 11(1–2), 41–49 (2005).
N. Hibino, T. Shin’oka, G. Matsumura, Y. Ikada, H. Kurosawa, The tissue-engineered vascular graft using bone marrow without culture, J Thorac Cardiovasc Surg 129(5), 1064–1070 (2005).
C. Huber, J. Batchelor, D. Fuchs, A. Hausen, A. Lang, D. Niederwieser, G. Reibnegger, P. Swetly, J. Troppmair, H. Wachter, Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon-gamma, J Exp Med 160(1), 310–316 (1984).
J. Hui, H. Ouyang, D. Hutmacher, J. Goh, E. Lee, Mesenchymal stem cells in the musculoskeletal tissue engineering: a review of recent advances in national University of Singapore, Ann Acad Med Singapore 34(2), 206–212 (2005).
I. Kan, E. Melamed, D. Offen, Integral therapeutic potential of bone marrow mesenchymal stem cells, Curr Drug Targets 6(1), 31–41 (2005).
Y. Kawakami, S. Aizawa, M. Hiramoto, I. Tsuboi, K. Wakasugi, Effects of neopterin on the proliferation and differentiation of hematopoietic progenitors derived from human umbilical cord blood, Pteridines 14(4), 129–132 (2003).
G. Pelled, G. Turgeman, H. Aslan, Z. Gazit, D. Gazit, Mesenchymal stem cells for bone gene therapy and tissue engineering, Curr Pharm Des 8(21), 1917–1928 (2002).
J. Plumas, L. Chaperot, M. Richard, J. Molens, J. Bensa, M. Favrot, Mesenchymal stem cells induce apoptosis of activated T cells, Leukemia 19(9), 1597–1604 (2005).
H. Rembold, W. Gyure, Biochemistry of the pteridines, Angew Chem Int Ed Engl 11(12), 1061–1072 (1972).
J. Ryan, F. Barry, J. Murphy, B. Mahon, Mesenchymal stem cells avoid allogeneic rejection, J Inflamm (Lond) 2(1), 8–18 (2005).
H. Wachter, D. Fuchs, A. Hausen, G. Reibnegger, G. Weiss, E. R. Werner, G. Werner-Felmayer, Neopterin: Biochemistry — Methods — Clinical application. De Gruyter, Berlin — New York, 1992
G. Werner-Felmayer, E. R. Werner, D. Fuchs, A. Hausen, G. Reibnegger, H. Wachter, Neopterin formation and tryptophan degradation by a human myelomonocytic cell line (THP-1) upon cytokine treatment, Cancer Res 50(10), 2863–2870 (1990).
W. Zhang, X. Walboomers, J. Wolke, Z. Bian, M. Fan, J. Jansen, Differentiation ability of rat postnatal dental pulp cells in vitro, Tissue Engineering 11(3–4), 357–368 (2005).
E. Zvetkova, E. Janeva, E. Nikolova, G. Milchev, A. Dikov, I. Tsenov, N. Bojilova, A. I. Hadjioloff, Hemopoietic colony-stimulating activity of ranopterins in murine bone marrow agar cultures, Compt Rend Acad Bulg Sci 44, 91–94 (1991).
E. Zvetkova, I. Tsenov, E. Katzarova, M. Bratanov, P. Angelova, I. Chowdhury, B. Nikolov, A. Dikov, In vitro proliferation of mouse bone marrow lymphocytes and stromal macrophages under the biological action of ranopterin (neopterin), Compt Rend Acad Bulg Sci 48, 81–84 (1995).
E. Zvetkova, Ranopterins — amphibia skin pteridines displaying hematopoietic, immunomodulatory and macrophageal proliferative biological activities, Pteridines 10, 178–189 (1999).
E. Zvetkova, D. Fuchs, E. Katzarova, M. Bakalska, M. Svetoslavova, B. Nikolov, Neopterin acting as a bone marrow stem cell factor on early common hematopoietic (myeloid) and stromal (dendritic, CD34+) cell progenitors in vitro, Pteridines 12, 135–139 (2001).
E. Zvetkova, D. Fuchs, E. Katzarova, M. Bakalska, M. Svetoslavova, B. Nikolov, I. Tsenov, I. Ilieva, Exogenously added in vitro neopterin is the bone marrow stem cell factor (BMSCF) acting on the early common hematopoietic (myeloid) and stromal (dendritic — CD34+) cell progenitors, Acta morphologica et anthropologica 6, 39–44 (2001).
E. Zvetkova, I. Zvetkov, A cytological method for the simultaneous staining of nucleoproteins and some cationic proteins, Acta Histochem 57, 1–13 (1976).
E. Zvetkova, J. Jelinek, Methylene blue-fast green staining of hematopoietic colonies in agar cultures, Gegenbaurs Morphol Jahrb 135, 779–793 (1989).
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Zvetkova, E., Gluhcheva, Y., Fuchs, D. (2006). Use of Neopterin as a Bone Marrow Hematopoietic and Stromal Cell Growth Factor in Tissue-Engineered Devices. In: Fisher, J.P. (eds) Tissue Engineering. Advances in Experimental Medicine and Biology, vol 585. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-34133-0_8
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DOI: https://doi.org/10.1007/978-0-387-34133-0_8
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