Research group for Hematology conducts research in the field of experimental hematology, immunology and stem cells. Main scientific program in the group is related to the investigations of cellular and molecular mechanisms involved in regulation of hematopoiesis in normal and pathological conditions, both in experimental animals and in humans.
Part of investigations is related to the study of the combined effects of biologicaly active molecules and/or (micro)environmental parameters on the survival, proliferation, differentiation and function of different hematopoietic cell populations from pluripotent and committed stem cells to the mature, functional hemopoietic end cells.
The research is also focused on isolation and characterization of mesenchymal stromal/stem cells (MSC) from various sources (bone marrow, peripheral blood, Wharton jelly, dental pulp, periodontal ligament, adipose tissue), as well as determination of their regenerative and modulatory capacities as potential candidates for application in cell therapy and tissue engineering.
The cellular and molecular changes of myeloproliferative neoplasms (MPN) are examined to achieve better diagnosis and detection of predisposition to progression of malignancy. The different experimental approaches in vitro and in vivo are applied, using human material and animal models. The characterization of gene expression at the transcriptional and translational level is observed in hematopoietic cells isolated from patients before and after therapy, to clarify the complex molecular network in transformed cell. In addition to genetic mutations, the research includes the role of oxidative stress and inflammation factors in the mechanism of MPN. The tendency to thrombosis and angiogenesis in bone marrow are determined by risk factors in the pathogenesis and progression of MPN. The genes expression and differentiation markers are followed during ontogenesis of hematopoietic progenitors.
PROJECTS & EDUCATION
- Regenerative and modulatory capacity of adult stem cells, 2011-2015, basic research
- The pathogenetic mechanism in haematological malignancies, 2011-2015, basic research
- Low-temperature plasma applications in biomedicine, environmental protection and Nano-technology, 2011-2015, integrative
- Cellular and molecular mechanisms involved in regulation of haematopoiesis, 2006-2010, basic research
- Appliance of plasma needle in medical and biological research and fast and reliable detection of volatile substances of human and herbal origin, 2008-2010, technological development
- Cellular and molecular mechanisms involved in regulation of hematopoiesis, 2006-2010, basic research
- Interactions of immobilized cells, tissues and biologically active molecules in bioreactor systems, 2006-2010, basic research
- Interaction of biologically active molecules and immobilized cell and tissue culture, 2002-2005, basic research
- Regulation of Hematopoiesis and Biologically Active Molecules, 2002-2005, basic
- Human culture-expanded adipose stromal/atem cells: serial expansion and maintenance of their proliferative, multipotential and regulatory properties, 2013-2015, Serbia-Portugal bilateral project
- A preliminary approach to the perinatal mesenchymal stem sell-based cellular therapy of Hereditary Haemorrhagic Telangiectasia, 2012-2013, Serbia-Spain bilateral project
- Immunomodulatory profiling of culture-expanded mesenchymal stem cells (MSCs) under low oxygen concentrations, 2011-2012, Serbia-Portugal bilateral project
- Research and development of blood derived Hemoglobin for animal usage – HEMIRON, 2008-2011, Eureka program 4486
- Health improvement in Serbia through reinforcement of biomedical science and technology (HISERBS), 2006-2009, Sixth EU’s Framework Programme for Research and Technological Development (FP6)
- Development, validation and modeling of a novel bioreactor system for cartilage tissue engineering, 2005-2008, Joint Research Project for the Scientific Co-operation between Eastern Europe and Switzerland (SCOPES)
- Maintenance of hematopoietic stem cell in hypoxia: role of IL-6 and its specific receptor, 2004-2005, joint Franco-Serbian research project within Pavle Savic programme with Faculty of Medicine, Bordeux-2, France
The group also participated in numerous innovation and strategic projects regarding development of new procedures and obtaining new biologically active substances, as well as following projects conducted in cooperation with industry:
- Hemoglobin-based blood substitute, with Hemofarm Concern, Vršac, 1994-1999.
- Development of technology for production of lipid emulsion for parenteral administration and liposomes for topical application in semi-industrial facility, with Hemofarm Concern, Vršac, 1998-2000.
- Establishing the therapeutic efficacy of polarized light on the healing of surgical wounds, Zepter Int, 1997-1998
- University of Belgrade, Faculty of Biology; Program: Biology; Module: Immunobiology; Subject: Immunohematology; Lecturer: Dr. Diana Bugarski
- University of Belgrade, Faculty of Biology; Program: Biology; Module: Cell and Tissue Biology; Subject: Cultivation of Cells and Tissues in vitro; Lecturers: Dr. Aleksandra Jauković and Dr. Jelena Krstić
- University of Belgrade, Faculty of Dental Medicine; Program: Multidisciplinary Approach to Solving Basic and Clinical Problems in Dentistry; Module: Cellular and Molecular Mechanisms of Pathogenesis and Treatment of Oral Diseases; Subjects: Stem Cell Biology and Proliferation, Differentiation and Regeneration of Oral Tissues; Lecturer: Dr. Diana Bugarski
- Pilot device for separation of ultra pure hemoglobin (99.999%) from erythrocytes (outdated human’s and porcine).
- Pilot device for semi-industrial production of Hemoglobin Standard (producer Hemofarm Concern, Vrsac Yu). (Product approved by ICSH, Atlanta, USA ).
- Blood substitute based on hemoglobin + carrier – preclinical tests on small animal:
- Liposomes for intravenous and topical usage:
- toxicological test
- tests of biosafety and biological efficacy on different animal models
- pharmacokinetics and pharmacodinamic tests
- Nanomicellar particles as carriers for drugs for intravenous and topical usage.
- Liposome antirid gel (Cosmetic collection “Missing”, Hemofarm Concern, Vrsac, Yu).
- Liposome SOD serum for intensive cosmetic care (Cosmetic collection “Missing”, Hemofarm Concern, Vrsac, Yu).
- Ultra pure hemoglobin from outdated human red cells and porcine red cells as a source for biologically derived iron for usage in prevention of anemia (supplements for human’s and animal’s food) and treatment of anemia.
- Verfahren zur Herstellung von Hemoglobin, Deutsches
Patentamt DE 197 07 508. Bugarski B , Dovezenski N (inventors), May 31, 2000.
- Hydrophobe nanotropfen mit gebundenen hamoglobinmolekulen in hydrophiler phase enthaltende emulsion als blutersatzstoff
(Emulsion containing hydrophobic nanodrops with bound hemoglobin molecules in a hydrophilic phase as a blood substitute)
Europaische Patentschrift EP 1 480 614 B1 15.10 2008 Patentblatt 2008&42
Bugarski B , Dovezenski N, Stojanovic N, Bugarski D (inventors)
Krstić J, Obradović H, Jauković A, Okić-Đorđević I, Trivanović D, Kukolj T, Mojsilović S, Ilić V, Santibañez JF, Bugarski D. Urokinase type plasminogen activator mediates Interleukin-17-induced peripheral blood mesenchymal stem cell motility and transendothelial migration. BBA-Mol Cell Res. 1853(2):431-444. 2015
Krstic J, Obradovic H, Kukolj T, Mojsilovic S, Okic-Dordevic I, Bugarski D, Santibanez JF. An Overview of Interleukin-17A and Interleukin-17 Receptor A Structure, Interaction and Signaling. Protein Pept Lett. 2015 Jun 17;22(7):570-8.
Krstić J, Trivanović D, Mojsilović S, Santibanez JF. Transforming Growth Factor-Beta and Oxidative Stress Interplay: Implications in Tumorigenesis and Cancer Progression. Oxid Med Cell Longev. 2015;2015:654594
Mojsilović S, Jauković A, Santibañez JF, Bugarski D. Interleukin-17 and Its Implication in the Regulation of Differentiation and Function of Hematopoietic and Mesenchymal Stem Cells. Mediat Inflamm. 2015;2015:470458.
rivanović D, Nikolić S, Kocić J, Krstić A, Mojsilović S, Ilić V, Okić-Djordjević I, Santibanez JF, Bugarski D. Characteristics of human adipose mesenchymal stem cells isolated from healthy and cancer affected people and their interactions with human breast cancer cell line MCF-7 in vitro. Cell Biol Int. 38(2):254-65, 2014
- Miletić M, Mojsilović S, Okić Đorđević I, Kukolj T, Jauković A, Santibañez JF, Jovčić G, Bugarski D. Mesenchymal stem cells isolated from human periodontal ligament. Arch Biol Sci. 66(1):261-271, 2014
- Trivanović D, Mojsilović S, Ilić V, Krstić J, Jauković A, Okić-Đorđević I, Santibanez JF, Jovčić G, Bugarski D. Immunomodulatory capacity of human mesenchymal stem cells isolated from adipose tissue, dental pulp, peripheral blood and umbilical cord Wharton’s Jelly. Centr Eur J Immunol. 38(4):421-9, 2013
- Miletic M, Mojsilovic S, Okic-Djordjevic I, Maletic D, Puac N, Lazovic S, Malovic G, Petrovic ZLj, Bugarski D. Effects of non-thermal atmospheric plasma on human periodontal ligament mesenchymal stem cells. Phys D Appl Phys. 46(34):345401, 2013
- Krstić J, Jauković A, Mojsilović S, Djordjevic IO, Trivanović D, Ilic V, Santibanez JF, Bugarski D. In vitro effects of IL-17 on angiogenic properties of endothelial cells in relation to oxygen levels. Cell Biol Int 37:1162-1170, 2013
- Trivanović D, Kocić J, Mojsilović S, Krstić A, Ilić V, Okić-Đorđević I, Santibane JF, Jovčić G, Terzić M, Bugarski D. Mesenchymal stem cells isolated from peripheral blood and umbilical cord Wharton’s jelly. Srp Arh Celok Lek. 141(3-4):178-186, 2013
- Okić-Đorđević I, Trivanović D, Krstić J, Jauković A, Mojsilović S, Santibanez JF, Terzić M, Vešović D, Bugarski D. GE132+Natural: Novel promising dietetic supplement with antiproliferative influence on prostate, colon, and breast cancer cells. J BUON 18(2):504-510, 2013
- Kocić J, Santibañez JF, Krstić A, Mojsilović S,Ilić V, Bugarski D. Interleukin-17 modulates myoblast cell migration by inhibiting urokinase type plasminogen activator expression through p38 mitogen-activated protein kinase. International Journal of Biochemistry & Cell Biology 45:464-475, 2013
- Krstic A, Kocic J, Ilic V, Mojsilovic S, Okic-Djordjevic I, Trivanovic D, Santibanez JF, Jovcic G, Bugarski D. Effects of IL-17 on erythroid progenitors growth: Involvement of MAPKs and GATA transcription factors. Journal of Biological Regulators and Homeostatic Agents, i26(4):641-652, 2012
- Kocić J., Bugarski D., Santibanez J.F. SMAD3 is essential for transforming growth factor-b1-induced urokinase plasminogen activator expression and migration in transformed keratinocytes Eur J Cancer 48:1550-1557, 2012
- Kocic J., Santibañez J.F., Krstic A., Mojsilovic S., Okic-Djordjevic I., Trivanovic D., Ilic V., Bugarski D. Interleukin 17 inhibits myogenic and promotes osteogenic differentiation of C2C12 myoblasts by activating ERK1,2. Biochimica et Biophysica Acta – Molecular Cell Research 1823:838-849, 2012
- Mojsilović S, Krstić A, Ilić V, Okić-Đorđević I, Kocić J, Trivanović D, Santibañez J, Jovčić G, Bugarski D. IL-17 and FGF signaling involved in mouse mesenchymal stem cell proliferation. Cell Tissue Research, 346(3):305-316, 2011
- Nikolic N., Krstic A., Trivanovic D., Mojsilovic S., Kocic J., Santibanez J.F., Jovcic G., Bugarski D. Mesenchymal stem cell properties of dental pulp cells from deciduous teeth. Arch Biol Sci, Belgrade 63(4):933-942, 2011
- Ilić V., Krstić A., Katić-Radivojević S., Jovčić G., Milenković P., Bugarski D. Syphacia obvelata modifies mitogen-activated protein kinases and nitric oxide synthases expression in murine bone marrow cells. Parasitol Int 59:82-88, 2010
- Krstić A., Santibanez J.F., Okić I., Mojsilović S., Kocić J., Jovčič G., Milenković P., Bugarski D. Combined effect of IL-17 and blockade of nitric oxide biosynthesis on haematopoiesis in mice. Acta Physiol 199:31-41, 2010
- Krstić A., Ilić V., Mojsilović S., Jovčić G., Milenković P., Bugarski D. p38 MAPK signaling mediates IL-17-induced nitric oxide synthase expression in bone marrow cells. Growth Factors 27(2): 79-90, 2009
- Krstić A., Vlaški M., Hammoud M., Chevaleyre J., Duchez P., Jovčić G., Bugarski D., Milenković P., Bourin P., Boiron J-M., Praloran V., Ivanović Z. Low O2 concentrations enhance the positive effect of IL-17 on the maintenance of erythroid progenitors during co-culture of CD34+ and mesenchymal stem cells. Eur Cytokine Netw 20:10-16, 2009
- Bugarski D., Krstić A., Mojsilović S., Vlaški M., Petakov M., Jovcic G., Stojanovic N., Milenkovic P. Signaling pathways implicated in hematopoietic progenitor cells proliferation and differentiation. Exp Biol Med 232:156-163, 2007
- Kovačević-Filipović M., Petakov M., Hermitte F., Debeisseat C., Krstić A., Jovčić G., Bugarski D., Lafarge X., Milenković P., Praloran V., Ivanović Z. Interleukin-6 (IL-6) and low O2 concentration (1%) synergize to improve the maintenance of hematopoietic srem cells (pre-CFC). J Cell Physiol 212:68-75, 2007
- Jovčić G., Bugarski D., Krstic A., Vlaski M., Petakov M., Mojsilovic S., Stojanovic N., Milenkovic P. The effect of interleukin-17 on hematopoietic cells and cytokine release in mouse spleen. Physiol Res 56:331-339, 2007
- Bugarski D., Jovcic G., Katic-Radivojevic S., Petakov M., Krstic A., Stojanovic N., Milenkovic P. Hematopoietic changes and altered reactivity to IL-17 in Syphacia obvelata-infected mice. Parasitol Int 55(2):91-97, 2006
- Bugarski D., Krstić A., Vlaški M., Petakov M., Jovcic G., Stojanović N., Milenković P. Interleukine-17-induced inhibitory effect on late stage murine erythroid bone marrow progenitors. Eur Cytokine Netw 15(3): 247-54, 2004
- Jovcic G., Bugarski D., Petakov M., Krstić A., Vlaški M., Stojanović N., Milenković P. In vivo effects of interleukin-17 on haematopoietic cells and cytokine release in normal mice. Cell Prolif 37(6): 401-12, 2004