研究领域
My research interests lie in the areas of stem cell bioprocessing, tissue engineering and mammalian cell bioprocessing.
Stem Cell Bioprocessing: The fundamental bottleneck of any bioprocess is the lack of real-time, on-line, in-situ, quantitative information with respect to cellular behaviour in culture. as a result, control, optimisation, and scale-up of bioprocesses are essentially manual (empirical), which results in sub-optimal productivity (i.e., inadequate cell expansion) and product quality (i.e., inconsistent cell phenotypes). To harness the immense potential of stem cells (SCS) in terms of their plasticity and expansion capabilities, the physiological activity in relation to the culture parameters (local) such as ph, dissolved oxygen, nutrients/metabolite concentrations and growth factor concentrations needs to be recorded quantitatively with the needed level of accuracy and subsequently evaluated in a biologically meaningful manner. My laboratory (BSEL), in collaboration with Dr. Drakakis (Bioengineering), Profs. Cass and Toumazou (IBE), Prof. Dame J. Polak (TERM), and Dr. Panoskaltsis (Haematology) is seeking to develop such a novel monitoring modality that allows the systematic development of clinically relevant culture systems and methodologies, which control and regulate stem cell self-renewal, expansion, differentiation, and death. Ultimately, such a breakthrough will lead to the engineering of reproducible, well-characterised, regenerated “designer” tissues and organs that meet the strict regulatory criteria for clinical applications. the engineering challenge involved in the fabrication of the proposed modality can only be met by the cross-fertilisation and amalgamation of expertise of cell biologists, engineers, scientists, and clinicians. Furthermore, my laboratory is currently working, in collaboration with Prof. Polak and Dr. Bishop(TERM), in developing intergated processes and culture systems for the expansion and differentiation of embryonic stem cells.
Tissue Engineering: Tissue engineering is an interdisciplinary field at the intersection of engineering, and biology and medicine. it requires the considerable input from biological scientists, who provide the insight to the various developmental control mechanisms of the cell and are able to manipulate the cell at a genetic level, and the contribution of material scientists who develop the structural scaffolds. My laboratory (BSEL) is seeking to provide integrated solutions to tissue engineering problems working close with material scientists (Dr. Bismarck) and modellers (Drs. Xu and Stepanek) to develop suitable scaffolds and culture systems for a variety of applications ranging from bone marrow, bone, cartilage, pneumocytes (Dr. Bishop), and cardiomyocytes (Prof. Polak), as well as developing ex vivo models for disease states, such as leukaemia (Dr. Panoskaltsis).
Mammalian Cell Bioprocessing: Animal cell technology is an area of rapid expansion and one that produces a wide range of high-value products, including vaccines, recombinant proteins, drugs for cardiovascular, respiratory and immune diseases, and monoclonal antibodies. commercial synthesis of monoclonal antibodies (mAb) represents one of the most important products in the biopharmaceutical industry because of their diagnostic and clinical applications. However, the production of industrial scale quantities of mAb is an expensive and challenging task. There are a number of complications that make it a difficult process to ensure that the culture is growing under optimal conditions at all times. Furthermore, the process control and optimisation in the hybridoma culture industry lags far behind the developments in other process industries; as a result, the current industrial control of hybridoma cell culture is still fundamentally manual. Complications arising in these systems include the requirement to grow cultures in complex media, the lack of on-line measurements for many of the key substrates, metabolites, and products, the limited and noisy nature of much of the available experimental data and the extremely complex underlying reaction system. Models of animal cell culture systems have a wide range of potential applications, such as analysis and prediction of experimental results, optimisation of culture conditions for prolonged viability, and perhaps most importantly, the investigation of fundamental metabolic processes and their subsequent elucidation. Our research programme sets out to integrate modelling, experiment design and validation, and control and optimisation into a single framework that would lead to increased productivity, regulated product quality, and reduced costs for mammalian cell culture systems. The integration of these three research tools represents a unique, novel, and interdisciplinary approach to addressing the complicated research and industrial problem of model-based control and optimisation of mammalian cell culture processes. This work is in collaboration with Prof. Stratos Pistikopoulos.
近期论文
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Fauzi I, Panoskaltsis N, Mantalaris A, 2016, In Vitro Differentiation of Embryonic Stem Cells into Hematopoietic Lineage: Towards Erythroid Progenitor's Production., Methods Mol Biol, Vol: 1341, Pages: 217-234
Klontzas ME, Kenanidis EI, MacFarlane RJ, Michail T, Potoupnis ME, Heliotis M, Mantalaris A, Tsiridis Eet al., 2016, Investigational drugs for fracture healing: preclinical & clinical data, EXPERT OPINION ON INVESTIGATIONAL DRUGS, Vol: 25, Pages: 585-596, ISSN: 1354-3784
Kostoglou M, Fuentes-Gari M, Garcia-Munzer D, Georgiadis MC, Panoskaltsis N, Pistikopoulos EN, Mantalaris Aet al., 2016, A comprehensive mathematical analysis of a novel multistage population balance model for cell proliferation, COMPUTERS & CHEMICAL ENGINEERING, Vol: 91, Pages: 157-166, ISSN: 0098-1354
Papathanasiou MM, Avraamidou S, Oberdieck R, Mantalaris A, Steinebach F, Morbidelli M, Mueller-Spaeth T, Pistikopoulos ENet al., 2016, Advanced Control Strategies for the Multicolumn Countercurrent Solvent Gradient Purification Process, AICHE JOURNAL, Vol: 62, Pages: 2341-2357, ISSN: 0001-1541
Reissis D, Quen OT, Cooper NC, Carasco CF, Gamie Z, Mantalaris A, Tsiridis Eet al., 2016, Current clinical evidence for the use of mesenchymal stem cells in articular cartilage repair, EXPERT OPINION ON BIOLOGICAL THERAPY, Vol: 16, Pages: 535-557, ISSN: 1471-2598
Savvopoulos S, Misener R, Panoskaltsis N, Pistikopoulos EN, Mantalaris Aet al., 2016, A Personalized Framework for Dynamic Modeling of Disease Trajectories in Chronic Lymphocytic Leukemia., IEEE Trans Biomed Eng, Vol: 63, Pages: 2396-2404
Zubairi SI, Mantalaris A, Bismarck A, Aizad Set al., 2016, Polyhydroxyalkanoates (PHAs) for tissue engineering applications: Biotransformation of palm oil mill effluent (POME) to value-added polymers, Jurnal Teknologi, Vol: 78, Pages: 13-29, ISSN: 0127-9696
Allenby MC, Tahlawi A, Dos Santos SB, Misener R, Hwang Y, Panoskaltsis N, Mantalaris Aet al., 2015, Development of a Hematopoietic Microenvironment for the Production of Red Blood Cells (RBCs) in a Novel 3D Hollow Fibre Bioreactor, TISSUE ENGINEERING PART A, Vol: 21, Pages: S15-S16, ISSN: 1937-3341
Allenby MC, Tahlawi A, dos Santos SB, Misener R, Hwang Y-S, Panoskaltsis N, Mantalaris Aet al., 2015, DEVELOPMENT OF AN EX VIVO BONE MARROW MIMICRY MICROENVIRONMENT IN A NOVEL 3D HOLLOW FIBRE BIOREACTOR, 44th Annual Scientific Meeting of the International-Society-for-Experimental-Hematology (ISEH), Publisher: ELSEVIER SCIENCE INC, Pages: S51-S51, ISSN: 0301-472X
Fuentes-Gari M, Misener R, Garcia-Munzer D, Velliou E, Georgiadis MC, Kostoglou M, Pistikopoulos EN, Panoskaltsis N, Mantalaris Aet al., 2015, A mathematical model of subpopulation kinetics for the deconvolution of leukaemia heterogeneity, JOURNAL OF THE ROYAL SOCIETY INTERFACE, Vol: 12, ISSN: 1742-5689
Fuentes-Gari M, Misener R, Georgiadis MC, Kostoglou M, Panoskaltsis N, Mantalaris A, Pistikopoulos ENet al., 2015, Selecting a Differential Equation Cell Cycle Model for Simulating Leukemia Treatment, INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH, Vol: 54, Pages: 8847-8859, ISSN: 0888-5885
Fuentes-Gari M, Velliou E, Misener R, Pefani E, Rende M, Panoskaltsis N, Mantalaris A, Pistikopoulos ENet al., 2015, A systematic framework for the design, simulation and optimization of personalized healthcare: Making and healing blood, COMPUTERS & CHEMICAL ENGINEERING, Vol: 81, Pages: 80-93, ISSN: 0098-1354
Fuentes-Gari M, Zemenides S, Misener R, Georgiadis MC, Pistikopouios EN, Mantalaris A, Panoskaltsis Net al., 2015, Use of Mathematical Modelling Indicates That Patients Treated for Acute Myeloid Leukaemia (AML) Are Undertreated When Ideal Body Weight Is Used to Dose Chemotherapy, 57th Annual Meeting of the American-Society-of-Hematology, Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
Fuentes-Garí M, Misener R, Pefani E, García-Münzer D, Kostoglou M, Georgiadis MC, Panoskaltsis N, Pistikopoulos EN, Mantalaris Aet al., 2015, Cell cycle model selection for leukemia and its impact in chemotherapy outcomes, Computer Aided Chemical Engineering, Vol: 37, Pages: 2159-2164, ISSN: 1570-7946
Fuentes-Gaŕ M, Misener R, Georgiadis MC, Kostoglou M, Panoskaltsis N, Pistikopoulos EN, Mantalaris Aet al., 2015, Chemotherapy optimization in Leukemia: Selecting the right mathematical models for the right biological processes, Pages: 534-539, ISSN: 1474-6670
Kang Y, Georgiou AI, MacFarlane RJ, Klontzas ME, Heliotis M, Tsiridis E, Mantalaris Aet al., 2015, Fibronectin stimulates the osteogenic differentiation of murine embryonic stem cells., J Tissue Eng Regen Med
Kiparissides A, Pistikopoulos EN, Mantalaris A, 2015, On the Model-Based Optimization of Secreting Mammalian Cell (GS-NS0) Cultures, BIOTECHNOLOGY AND BIOENGINEERING, Vol: 112, Pages: 536-548, ISSN: 0006-3592
Klontzas ME, Kenanidis EI, Heliotis M, Tsiridis E, Mantalaris Aet al., 2015, Bone and cartilage regeneration with the use of umbilical cord mesenchymal stem cells, EXPERT OPINION ON BIOLOGICAL THERAPY, Vol: 15, Pages: 1541-1552, ISSN: 1471-2598
Kostoglou M, Fuentes-Gari M, Garcia-Muenzer D, Georgiadis MC, Panoskaltsis N, Pistikopoulos EN, Mantalaris Aet al., 2015, Mathematical analysis of multistage population balances for cell growth and death, 12TH INTERNATIONAL SYMPOSIUM ON PROCESS SYSTEMS ENGINEERING AND 25TH EUROPEAN SYMPOSIUM ON COMPUTER AIDED PROCESS ENGINEERING, PT C, Vol: 37, Pages: 2105-2110, ISSN: 1570-7946
Muenzer DGG, Ivarsson M, Usaku C, Habicher T, Soos M, Morbidelli M, Pistikopoulos EN, Mantalaris Aet al., 2015, An unstructured model of metabolic and temperature dependent cell cycle arrest in hybridoma batch and fed-batch cultures, BIOCHEMICAL ENGINEERING JOURNAL, Vol: 93, Pages: 260-273, ISSN: 1369-703X
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