Imperial College
South Kensigton Campus
SW7 2AZ
London
 | m.rende@imperial.ac.uk |
As biologist experiencing a PhD in Chemical Engineering and Materials, I have had the possibility to combine both science and engineer skills to gain experience on the use of platforms to develop ex vivo culture systems.
Past work included the use of human, pig and rat hepatic cells in biohybrid systems, for the study of hepatocyte growth, adhesion and functions. Albumin, immunoglobulin, urea synthesis together with drug (diazepam, paracetamol, diclofenac, rofecoxib, hyperforin, isoliquiriteginin) biotransformation ability of the cells in culture on the biomimetic surfaces and/or in permeable membrane (flat, tubular and hollow fibers) bioreactors, have been assessed. Working for many years in engineering departments, gave me the opportunity to gain competencies on polymeric film and scaffold preparation and characterization besides with material surface modification, in order to direct cell growth and differentiation.
Following the experience gained, research moved later with my PhD towards the influence of membrane surface properties, on the growth of hamster hippocampal neuronal cells. The goal of this work was to achieve a biohybrid system constituted by membranes and hippocampal neurons, for in vitro regeneration of neuronal tissue as substitute of human brain functions. In particular, I observed that hippocampal neurons can adhere, polarise and develop neurites of different lengths, depending on the topographical characteristics of the surface on which they are grown. Furthermore, by changing their morphology and degree of neurite outgrowth, they displayed differences in specific metabolic functions, such as glucose consumption and secretion of brain-derived neurotrophic factor (BDNF). Along with these behaviours, I observed that hippocampal morphogenesis, metabolism and the expression of specific neuronal markers, was affected by the addition of an anxiolytic drug (flunitrazepam) to the culture.
Most recently, I have faced the challenge to culture peripheral/umbilical cord blood mononuclear cells into ex vivo scaffolds based system, to be able to mimic the bone marrow microenvironment, allowing the growth and differentiation of hematopoietic progenitor cells in mature blood cells. Cultures were run in the absence of cytokines, leaving cells to growth in a closer physiological environment meanwhile reducing bias. The bone marrow biomimicry was also used to culture human peripheral blood and bone marrow acute myeloid leukemic cells, isolated from patient samples. The unique environment created inside the scaffold provided a niche-like tool, which permitted leukemic growth as well as the normal cell, demonstrating his feasibility as potential human model for a better understanding of cellular and microenvironmental determinants of leukemogenesis. These ex vivo platforms have not only been used in static culture conditions, but also in bioreactors, wherein an incorporated perfusion system based on membranes, allowed a continuous nutrients and metabolites exchange, similarly to the bone marrow vasculature. The continuous perfusion supported both human hematopoietic and leukemic cell growth at a higher rate than static, delivering a most cost-effective production of normal/abnormal blood cells for potential biological therapies. Membrane bioreactors can be a step forward in ex vivo culture, as are suitable for long-term in vitro cultures in tissue-like constructs, wherein membranes working as vessel permit optimal exchanges avoiding mass –i.e. gas/nutritional support and waste removal – limitations; can also provide an alternative tool to conventional static culture to understand cell bioprocessing and aim drug screening.Although efficiently succeeding during my career with many ex vivo cell culture models, yet further bioengineering challenges have to be accomplished to deliver good quality research on regenerative medicine.
My future career plans aim to both academia and companies looking for a passionate and talented researcher interested on leading a research group that wishes to develop skills on ex vivo platforms, most likely perfused, for culture of human cells. Working as in vitro substitutes, these bioengineered models can potential contribute to regenerative medicine, meeting both industry and medical needs on understanding human cell biology, test the efficacy and toxicity of new biomolecules, screen drugs and deliver new therapies.
Past work included the use of human, pig and rat hepatic cells in biohybrid systems, for the study of hepatocyte growth, adhesion and functions. Albumin, immunoglobulin, urea synthesis together with drug (diazepam, paracetamol, diclofenac, rofecoxib, hyperforin, isoliquiriteginin) biotransformation ability of the cells in culture on the biomimetic surfaces and/or in permeable membrane (flat, tubular and hollow fibers) bioreactors, have been assessed. Working for many years in engineering departments, gave me the opportunity to gain competencies on polymeric film and scaffold preparation and characterization besides with material surface modification, in order to direct cell growth and differentiation.
Following the experience gained, research moved later with my PhD towards the influence of membrane surface properties, on the growth of hamster hippocampal neuronal cells. The goal of this work was to achieve a biohybrid system constituted by membranes and hippocampal neurons, for in vitro regeneration of neuronal tissue as substitute of human brain functions. In particular, I observed that hippocampal neurons can adhere, polarise and develop neurites of different lengths, depending on the topographical characteristics of the surface on which they are grown. Furthermore, by changing their morphology and degree of neurite outgrowth, they displayed differences in specific metabolic functions, such as glucose consumption and secretion of brain-derived neurotrophic factor (BDNF). Along with these behaviours, I observed that hippocampal morphogenesis, metabolism and the expression of specific neuronal markers, was affected by the addition of an anxiolytic drug (flunitrazepam) to the culture.
Most recently, I have faced the challenge to culture peripheral/umbilical cord blood mononuclear cells into ex vivo scaffolds based system, to be able to mimic the bone marrow microenvironment, allowing the growth and differentiation of hematopoietic progenitor cells in mature blood cells. Cultures were run in the absence of cytokines, leaving cells to growth in a closer physiological environment meanwhile reducing bias. The bone marrow biomimicry was also used to culture human peripheral blood and bone marrow acute myeloid leukemic cells, isolated from patient samples. The unique environment created inside the scaffold provided a niche-like tool, which permitted leukemic growth as well as the normal cell, demonstrating his feasibility as potential human model for a better understanding of cellular and microenvironmental determinants of leukemogenesis. These ex vivo platforms have not only been used in static culture conditions, but also in bioreactors, wherein an incorporated perfusion system based on membranes, allowed a continuous nutrients and metabolites exchange, similarly to the bone marrow vasculature. The continuous perfusion supported both human hematopoietic and leukemic cell growth at a higher rate than static, delivering a most cost-effective production of normal/abnormal blood cells for potential biological therapies. Membrane bioreactors can be a step forward in ex vivo culture, as are suitable for long-term in vitro cultures in tissue-like constructs, wherein membranes working as vessel permit optimal exchanges avoiding mass –i.e. gas/nutritional support and waste removal – limitations; can also provide an alternative tool to conventional static culture to understand cell bioprocessing and aim drug screening.Although efficiently succeeding during my career with many ex vivo cell culture models, yet further bioengineering challenges have to be accomplished to deliver good quality research on regenerative medicine.
My future career plans aim to both academia and companies looking for a passionate and talented researcher interested on leading a research group that wishes to develop skills on ex vivo platforms, most likely perfused, for culture of human cells. Working as in vitro substitutes, these bioengineered models can potential contribute to regenerative medicine, meeting both industry and medical needs on understanding human cell biology, test the efficacy and toxicity of new biomolecules, screen drugs and deliver new therapies.
