Founding Director of the Pharmaceutical Production Research Facility (PPRF)
P.Eng, Alberta, Canada
1. CIC activities
2. scientific and technical contributions
3. management of science or technology teaching
4. promotion of public awareness of chemistry, chemical engineering or chemical technology.
Candidates should have made contributions in all four areas and outstanding contributions in at least one area.
DR. BEHIE'S research expertise is in chemical reaction engineering as applied to a number of areas including biomedical and tissue engineering, in addition to multiphase chemical reactors found in the chemical processing industry.
Although these areas appear to be unrelated, the common link that ties them together is new reactor technology in both biomedical engineering and chemical engineering. In the biomedical area, Dr. Behie is the founding Director of the Pharmaceutical Production Research Facility (PPRF) located on the 5th floor of the Biological Sciences Building at the University of Calgary (www.pprf.ca). Through this tissue culture laboratory (with bioreactor pilot plant attached), Dr. Behie has developed a great deal of experience in understanding the nature of bioreactor problems found in the large-scale production of biopharmaceuticals. His main projects presently include developing new bioreactor protocols for growing and characterizing human adult stem cells, also called tissue specific stem cells [i.e. including human neural stem cells (hNSCs), human mesenchymal stem cells (hMSCs) from various human tissues, human brain cancer stem cells (hCSCs) and pancreatic progenitor cells]. Recently he has extended this research to include the development of bioengineering strategies for growing newly discovered induced pluripotent stem cells (iPSCs)].
Dr. Behie presently has powerful collaborations with a number of clinicians and researchers including –
(i) Dr. Ivar Mendez (clinician, neurosurgeon at the Queen Elizabeth II Hospital and Director of the Cell Restoration Laboratory at the Brain Repair Center of Dalhousie University in Halifax, Nova Scotia). A successful project on the transplantation of bioreactor-produced human neural stem/progenitor cells into animal models has been ongoing for several years targeting the design of clinical trials for the treatment of Parkinson's disease (Baghbaderani et al., 2011a, Baghbaderani et al., 2011b, Mukhida et al., 2008; Mukhida et al., 2007) and Huntington's disease (McLeod et al., 2012). In other words, PPRF researchers have grown human brain tissue (i.e. neural stem/progenitor cells, also called human neural precursor cells, hNPCs) in large-scale bioreactors, an important step that may lead to the transplantation of stem cells or their differentiated progeny into the human brain to treat such terrible diseases as Parkinson's and Huntington's diseases. Recently, new and successful preclinical trial projects were completed. Firstly, key bioengineering papers have been published recently describing a bioreactor technology platform for the expansion of human neural precursor cells in large-scale bioreactors for the treatment of neurodegenerative disorders (McLeod et al., 2012, Baghbaderani et al., 2011a; Baghbaderani et al, 2011b; Baghbaderani et al., 2010). These studies have demonstrated that clinical quantities of neural cells can be produced under standardized conditions in computer-controlled suspension bioreactors. Secondly, another of our papers published in the journal Stem Cells (Mukhida et al., 2007) presented an important finding which has huge implications for the development of a new treatment for spinal cord pain (i.e. 65% of patients with spinal cord injuries alone have intractable spinal cord pain). Specifically, hNPCs were first expanded in suspension bioreactors, then differentiated into gamma-aminobutyric acid (GABA)-producing neurons (i.e. GABAergic neurons) and finally transplanted intraspinally into a rodent model of neuropathic pain.
(ii) Dr. Gregory Foltz (clinician, neurosurgeon at the Swedish Medical Center and Director of the Ben and Catherine Ivy Center for Advanced Brain Tumor Treatment in Seattle, Washington) and Dr. Leroy Hood, the President and Co-Founder of the world renown Institute for Systems Biology (ISB) in Seattle. This research initiative aims to establish an effective means of increasing human brain cancer stem cell numbers in suspension bioreactors operated under computer-control (Panchalingam et al., 2011; Panchalingam et al., 2010). Recent evidence suggests that normal neural stem cells can undergo a transformation to become brain cancer stem cells, and that brain tumour growth is fuelled by the proliferation of these rare "tumour initiating cells, TICs" that retain their neural stem cell properties. Like adult stem cells, cancer stem cells are thought to produce a phenotypically heterogeneous collection of progenitor cells and terminally differentiated cells. However, unlike normal adult stem cells, they do so in an uncontrolled manner. Whereas cancer stem cells divide infrequently, their subsequent progenitors may divide rapidly in vivo, resulting in the formation of a brain tumour which consists of less than 0.1% cancer stem cells. Current cancer therapies focus primarily upon the eradication of these rapidly dividing cells, but often result in the reappearance of a tumor mass after treatment which suggests the survival of the tumour initiating cells (i.e. the cancer stem cells). The development of more effective therapies for brain cancers may therefore ultimately depend upon the successful targeting of brain cancer stem cells for eradication. A major obstacle preventing the development of such treatments is the limited availability of these cells, restricting analyses to assays requiring low cell numbers. Moreover, it now appears that specific human brain cancers (e.g. glioblastoma multiform) are genetically different from patient-to-patient. Hence, new treatments for patients with the same type of brain cancer may have to be tailored to individual patients. Due to similarities between human neural stem cells and brain cancer stem cells, it is anticipated that significant advancements made at PPRF in the expansion of human neural stem cells in suspension bioreactors will provide a good bioengineering basis for investigating brain cancer stem cell expansion and characterization.
(iii) Dr. Lawrence Rosenberg (clinician, Professor of Surgery and Medicine; Director, Division of Surgical Research, McGill University, and A.G. Thompson Chair of Surgical Research, McGill University and Chief of Surgical Services, Jewish General Hospital, Montreal). This collaboration has been funded by the CIHR Regenerative Medicine Program. One aim is to further extend our work on expanding a population of pancreatic progenitor cells that may be used to treat Type 1 diabetes (Jung et al., 2012a, Jung et al., 2012b, Jung et al., 2012c, Bodnar et al., 2006, Jung et al., 2009). The overall objective of the research is the large-scale production of an unlimited supply of functional insulin-producing beta cells in computer-controlled bioreactors. Moreover, Dr. Behie and his colleagues at PPRF have already succeeded in culturing over long periods of time porcine islet-like tissue in a suspension culture bioreactor. This tissue had all the endocrine tissue types found in a pancreatic islet. In fact, the beta cell population (i.e. cells that produce insulin) increased by 700% over a culture time of 9 days in bioreactors. These results have important implication in terms of providing new bioreactor technologies to producing new human pancreatic islet-like structures for the treatment of Type 1 diabetes.
More recently, our recent research efforts have been expanded to include the bioengineering of human pancreatic mesenchymal stem cells (P-hMSCs) as an alternate approach in treating diabetes (Jung et al., 2012a, Jung et al., 2012b, Jung et al., 2012c). Human mesenchymal stem cells (hMSCs) have many potential applications in tissue engineering and regenerative medicine. In fact, much evidence in the literature makes compelling arguments for their use in cell-based therapies not only for the treatment of diabetes, but also for such diseases as multiple sclerosis (MS).
(iii) Dr. Brent Reynolds (world prominent neuroscientist, Department of Neurosurgery, McKnight Brain Institute, University of Florida, Gainesville, Florida). This collaboration deals with our newly developed protocol for the large-scale production of pure populations of human primitive neurons called neuroblast to be used as a renewable source of cells for - (a) drug screening, (b) neurotoxicology, and (c) cell replacement therapy for the treatment of many diseases of the central nervous system (e.g. Parkinson's disease). Very recently, we have refined our procedure for producing pure human neuroblast populations and differentiated them into functional neurons for transplantation. At present, we are planning, along with our neurosurgeon colleague Dr. Ivar Mendez, to reproduce our cell transplantation study which appeared in our paper published in Stem Cells (Mukhida et al. , 2007) to treat mechanical allodynia in an animal model of neuropathic pain.
(iv) Dr. António Salgado (Medical Researcher, Neurosciences Research Domain, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Portugal). This new collaboration is a basic study which deals with the effects of conditioned culture media derived from the dynamic culture of human bone marrow derived mesenchymal stem cells (BM-hMSCs) on the neuronal and glial differentiation of human neural stem cells. We are presently investigating experimental procedures to modulate the secretome of hMSCs through applying different culture environments, particularly a dynamic culture system using suspension cultures of microcarriers.
(v) Dr. Bernard Thébaud [clinician in Pediatrics, Division of Neonatology, Children's Hospital of Eastern Ontario, Professor of Pediatrics, University of Ottawa and Senior Scientist, Regenerative Medicine, Ottawa Hospital Research Institute (OHRI)]). This newest collaboration deals with the very serious problem for babies who are born prematurely and who experience respiratory problems, having developed chronic lung disease (i.e. bronchopulmonary dysplasia, BPD). A baby is not born with BPD, but develops it as a consequence of prematurity and progressive lung inflammation. Although most babies recover fully, BPD can be a serious condition requiring intensive medical care. The driving force behind this research is a seminal publication by Dr. Thébaud and colleagues (Stem Cells and Development, 2012, Epub ahead of print, DOI 10.1089/scd.2010.0566) in which they demonstrated that bone marrow derived mesenchymal stem cells (BM-MSCs) prevent lung injury in an O2-induced animal model of BPD. They concluded that ex vivo preconditioning enhances the paracrine effect of BM-MSCs and opens new therapeutic options for stem cell-based therapies. Hence, the big and urgent push in our laboratories right now is to translate the animal models studies into a procedure using human stem cells which can be applied in the clinic to premature babies with BPD. To achieve this goal, we must develop a clinically acceptable and safe procedure to produce MSCs in computer-controlled bioreactors which can be used in the clinic.
Jung S, Teixeira FG, Panchalingam KM, Salgado AJ, Behie LA, "Potential Therapeutic Properties of Human Mesenchymal Stem Cells", Journal for Clinical Studies 4(6), 36-40 (2012).
McLeod MC, Kobayashi NR, Sen A, Baghbaderani BA, Sadi D, Utalia R, Behie LA, Mendez I, "Transplantation of GABAergic Cells Derived from Bioreactor-Expanded Human Neural Precursor Cells Restores Motor and Cognitive Behavioural Deficits in a Rodent Model of Huntington's Disease", Cell Transplantation (Epub ahead of print, DOI: 10.3727/096368912X658809, 55 pages, available online Nov 1, 2012).
Jung S, Sen A., Rosenberg L., Behie LA, "Human Mesenchymal Stem Cell Culture: Rapid and Efficient Isolation and Expansion in a Defined Serum-Free Medium", Journal of Tissue Engineering and Regenerative Medicine 6(5), 391-403 (2012).
Jung S, Sen A Panchalingam K, Wuerth R, Rosenberg L., Behie LA, " Large-Scale Production of Human Mesenchymal Stem Cells for Clinical Applications ", Biotechnology and Applied Biochemistry 59(2), 106-120 (2012).
Jung S, Sen A., Panchalingam K, Rosenberg L., Behie LA, " Ex vivo Expansion of Human Mesenchymal Stem Cells in Defined Serum-Free Media ", Stem Cells International DOI: 10.1155/2012/123030, 21 pages, free access article (2012).
Baghbaderani BA, Mukhida K, Hong M, Mendez I, Behie LA, "A Review of Protocols for Human Neural Precursor Cell Expansion in Preparation for Clinical Trials", Current Stem Cell Research & Therapy 6(3), 229-254 (2011a).
Baghbaderani BA, Mukhida K, Hong M, Mendez I, Behie LA, "New Bioengineering Insights into Human Neural Precursor Cell Expansion in Culture, Biotechnology Progress 27(3), 776 (2011b).
Behie LA, "Bioengineering the Future", invited contribution to the book Dreams and Due Diligence - Till and McCulloch's Stem Cell Discovery, Publ University of Toronto Press, ISBN: 978-1-4426-4485-4, 120 (2011).
Panchalingam K, Paramchuk W, Hothi P, Nameeta Shah N, Hood L, Foltz G, Behie LA, "Production of Human Glioblastoma-Derived Cancer Stem Cell Tissue in Suspension Bioreactors to Facilitate the Development of Novel Oncolytic Therapeutics, invited Chapter in the book Cancer Stem Cells: The Cutting Edge, InTech Open Access Publisher, Vienna, Austria, ISBN: 978-953-307-580-8 (2011).
Jung S, Sen A., Rosenberg L., Behie LA, "Identification of Growth and Attachment Factors for the Serum-Free Isolation and Expansion of Human Mesenchymal Stem Cells", Cytotherapy 12(5) 637-657 (2010).
Panchalingam KM, Paramchuk WJ, Chiang CK, Shah N, Madan A, Hood L, Foltz G, Behie LA, "Bioprocessing of Human Glioblastoma Brain Cancer Tissue", Tissue Engineering 16(4), 1169-1177 (2010).
Baghbaderani BA, Mukhida K, Sen A, Kallos MS, Hong M, Mendez I, Behie LA. "Bioreactor Expansion of Human Neural Precursor Cells in Serum-Free Media Retains Neurogenic Potential", Biotechnology and Bioengineering 105(4), 823-833 (2010). [Figure from this paper was chosen for journal cover]
Sen A, Kallos MS, Behie LA, "Bioprocess Engineering of Neural Stem Cells", Wiley Encyclopedia of Industrial Biotechnology, Ed MC Flickinger, Publ John Wiley & Sons, ISBN: 978-0-471-79930-6 (2010).
Baghbaderani BA, Sen A, Kallos MS, Behie LA, "Bioengineering Protocols for Neural Precursor Cell Expansion", Chapter in the book Protocols for Neural Cell Culture (4th Edition), Ed L Doering, Publ The Humana Press (4th Edition), Series: Springer Protocols Handbooks, ISBN: 978-1-60761-291-9 (2010).
Kutlu B, Kayali A, Jung S, Parnaud G, Baxter D, Glusman G, Goodman N, Behie LA, Hayek A, Hood L, "Meta Analysis of Gene Expression in Human Pancreatic Islets After in vitro Expansion", Physiological Genomics 39(1), 72-81 (2009).
Jung S, Sen A, Kallos MS, Behie LA, Rosenberg L, Kutlu B, Goodman N, "Large-Scale Production of Functional Beta Cells from Stem/Progenitor Cells in Suspension Bioreactors", Chapter 29 in the book The Bioartificial Pancreas and Other Biohybrid Therapies, Eds JP Hallé, P de Vos, L Rosenberg, Publ Research Signpost, ISBN: 978-81-7895-415-8 (2009).
Mukhida K, Hong M, Miles G, Phillips T, Baghbaderani BA, McLeod M, Kobayashi A, Sen A, Behie LA, Brownstone R, Mendez I, "A Multitarget Basal Ganglia Dopaminergic and GABAergic Transplantation Strategy Enhances Behavioural Recovery in Parkinsonian Rats", Brain 131(8), 2106-2126 (2008).
Baghbaderani BA, Mukhida K, Sen A, Hong M, Mendez I, Behie LA, "Expansion of Human Neural Precursor Cells in Large-Scale Bioreactors for the Treatment of Neurodegenerative Disorders", Biotechnology Progress 24(4), 859-870 (2008).
Mukhida K, Baghbaderani BA, Hong M, Lewington M, Phillips T, McLeod M, Sen A, Behie LA, Mendez I, "Survival, Differentiation and Migration of Bioreactor-Expanded Human Neural Precursor Cells in a Model of Parkinson Disease in Rats", Journal of Neurosurgical Focus 24(3-4): E8, 1-17 (2008).
Mukhida K, Mendez I, McLeod M, Kobayashi N, Milne B, Baghbaderani BA, Sen A, Behie LA and Hong M, "Spinal GABAergic Transplants Attenuate Mechanical Allodynia in a Rat Model of Neuropathic Pain", Stem Cells 25(11), 2874-2885 (2007).
Youn BS, Arindom S, Behie LA, Clarke I, Dirks PB, Basik M, invited FEATURE ARTICLE, "Bioprocessing of Cancer Stem Cells", BioProcessing Journal 6(2), 21-29 (2007).
Petropavlovskaia M, Bodnar CA, Behie LA, Rosenberg L, "Pancreatic Small Cells: Analysis of Quiescence, long-Term Maintenance and Insulin Expression in Vitro", Experimental Cell Research 313(5), 931-942 (2007).
BESc. 1968 in Chemical & BioChemical Engineering, University of Western Ontario (UWO)
MESc. 1969 in Chemical Engineering, Western University
PhD. 1972 in Chemical Engineering, Western University
NATO Postdoctoral Fellowship 1973 (University of Cambridge, England