Microparticles as Cellular Communicators to Empower Therapies: the Case of Megakaryocytic Microparticles
Event details
| Date | 08.12.2014 |
| Hour | 11:00 |
| Speaker | Prof. Eleftherios Terry Papoutsakis, University of Delaware, Newark, DE (USA) |
| Location | |
| Category | Conferences - Seminars |
DISTINGUISHED LECTURE IN BIOLOGICAL ENGINEERING
Abstract:
A long-standing goal in cell-culture technologies is the ability to produce human blood cells for transfusion medicine. Another important goal is to develop robust differentiation technologies of stem cells, technologies that could be transferred to the clinic but also used in in vitro investigational experimentation. Among blood cells, platelets, needed for blood coagulation and vascular repair, are an expensive “product” in limited supply. Production of platelets in a “blood factory” is recognized as a grand challenge that remains elusive. Platelets derive from polyploid megakaryocytes (Mks) in the bone marrow and lung vasculature, under biomechanical forces. We will show how important these forces are for producing functional platelets and their precursors, as well as small, anuclear particles, Mk microparticles (MkMPs)*. MkMP generation was dramatically enhanced (up to 47 fold) by shear flow. Significantly, co-culture of MkMPs with hematopoietic stem and progenitor cells (HSPCs) promoted HSPC differentiation to Mks without exogenous thrombopoietin, thus identifying, for the first time, a novel and previously unexplored potential physiological role for MkMPs. This demonstrates the extraordinary ability of these MkMPs in programming HSPCs. I will discuss our efforts to understand the mechanisms by which MkMPs target and act upon cells. How general is the production and biological activity of MPs? Most cells release into the extracellular environment these very small MPs (typically less than 1 micron) under some stress or activation process. MPs result from direct budding off the the plasma membrane, and are increasingly recognized as important players in intercellular communication by transferring proteins, lipids, RNA, and perhaps DNA, between cells. They do so with good target specificity and thus, one can argue for producing and using them for regenerative-medicine applications, as well as in experimental investigations to deliver “cargo” to specific cell types.
* Jiang, J; Woulfe, DS; Papoutsakis, ET. Shear enhances thrombopoiesis and formation of microparticles that induce megakaryocytic differentiation of stem cells BLOOD 124: 2094-2103 (SEP 25 2014).
Bio:
Dr. Papoutsakis comes to UD from Northwestern University, where he served as Walter P. Murphy Professor of Chemical and Biological Engineering and also was a member of the Lurie Comprehensive Cancer Center of the Northwestern University Medical School. Before that, he was a member of the Rice University faculty.
His research focuses on areas of systems biology, metabolic engineering, experimental and computational genomics with applications in stem-cell biology and prokaryotic biology for the production of biofuels and chemicals from biomass.
A fellow of the American Academy of Microbiology and the American Association for the Advancement of Science and a founding fellow of the American Institute of Medical and Biological Engineers, Papoutsakis also has received several awards, including the Amgen Biochemical Engineering Award and the Merck Cell Culture Engineering Award, both from the from Engineering Conferences International; the Alpha Chi Sigma Award and the Food, Pharmaceutical and Bioengineering Award, both from the American Institute of Chemical Engineers; and the Marvin Johnson Award and the Van Lanen Award, both from the Biochemical Technology Division of the American Chemical Society. Papoutsakis has published extensively in his field and served as editor-in-chief of Biotechnology and Bioengineering. He also serves on the advisory boards of four journals in the field of biotechnology and tissue engineering, and on the organizing committees or advisory boards of many international meetings. He has authored several issued and pending patents. He has served or serves on the Scientific Advisory Boards (SAB) of four biotechnology companies. He consults regularly and offers expert witness services in the field of biotechnology, and biomedical sciences more broadly.
A graduate of the National Technical University of Athens, Greece, Papoutsakis received his Master's and Doctoral degrees from Purdue University.
Abstract:
A long-standing goal in cell-culture technologies is the ability to produce human blood cells for transfusion medicine. Another important goal is to develop robust differentiation technologies of stem cells, technologies that could be transferred to the clinic but also used in in vitro investigational experimentation. Among blood cells, platelets, needed for blood coagulation and vascular repair, are an expensive “product” in limited supply. Production of platelets in a “blood factory” is recognized as a grand challenge that remains elusive. Platelets derive from polyploid megakaryocytes (Mks) in the bone marrow and lung vasculature, under biomechanical forces. We will show how important these forces are for producing functional platelets and their precursors, as well as small, anuclear particles, Mk microparticles (MkMPs)*. MkMP generation was dramatically enhanced (up to 47 fold) by shear flow. Significantly, co-culture of MkMPs with hematopoietic stem and progenitor cells (HSPCs) promoted HSPC differentiation to Mks without exogenous thrombopoietin, thus identifying, for the first time, a novel and previously unexplored potential physiological role for MkMPs. This demonstrates the extraordinary ability of these MkMPs in programming HSPCs. I will discuss our efforts to understand the mechanisms by which MkMPs target and act upon cells. How general is the production and biological activity of MPs? Most cells release into the extracellular environment these very small MPs (typically less than 1 micron) under some stress or activation process. MPs result from direct budding off the the plasma membrane, and are increasingly recognized as important players in intercellular communication by transferring proteins, lipids, RNA, and perhaps DNA, between cells. They do so with good target specificity and thus, one can argue for producing and using them for regenerative-medicine applications, as well as in experimental investigations to deliver “cargo” to specific cell types.
* Jiang, J; Woulfe, DS; Papoutsakis, ET. Shear enhances thrombopoiesis and formation of microparticles that induce megakaryocytic differentiation of stem cells BLOOD 124: 2094-2103 (SEP 25 2014).
Bio:
Dr. Papoutsakis comes to UD from Northwestern University, where he served as Walter P. Murphy Professor of Chemical and Biological Engineering and also was a member of the Lurie Comprehensive Cancer Center of the Northwestern University Medical School. Before that, he was a member of the Rice University faculty.
His research focuses on areas of systems biology, metabolic engineering, experimental and computational genomics with applications in stem-cell biology and prokaryotic biology for the production of biofuels and chemicals from biomass.
A fellow of the American Academy of Microbiology and the American Association for the Advancement of Science and a founding fellow of the American Institute of Medical and Biological Engineers, Papoutsakis also has received several awards, including the Amgen Biochemical Engineering Award and the Merck Cell Culture Engineering Award, both from the from Engineering Conferences International; the Alpha Chi Sigma Award and the Food, Pharmaceutical and Bioengineering Award, both from the American Institute of Chemical Engineers; and the Marvin Johnson Award and the Van Lanen Award, both from the Biochemical Technology Division of the American Chemical Society. Papoutsakis has published extensively in his field and served as editor-in-chief of Biotechnology and Bioengineering. He also serves on the advisory boards of four journals in the field of biotechnology and tissue engineering, and on the organizing committees or advisory boards of many international meetings. He has authored several issued and pending patents. He has served or serves on the Scientific Advisory Boards (SAB) of four biotechnology companies. He consults regularly and offers expert witness services in the field of biotechnology, and biomedical sciences more broadly.
A graduate of the National Technical University of Athens, Greece, Papoutsakis received his Master's and Doctoral degrees from Purdue University.
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