Leo A. Behie

Professor

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Awards / Accolades   

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.ucalgary.ca/pprf). 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 neural stem cells (hNSCs), mesenchymal stem cells (hMSCs), brain cancer stem cells (hCSCs), pancreatic progenitor cells and liver stem 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 (a neurosurgeon and Director of the Cell Restoration Laboratory at the Brain Repair Center of Dalhousie University in Halifax). 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 (Mukhida et al., 2008; Mukhida et al., 2007) and Huntington's disease (McLeod et al., 2011). 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. Very 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 neural precursor cells in large-scale bioreactors for the treatment of neurodegenerative disorders (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. Greg Foltz (a neurosurgeon at the Swedish Medical Center and Director of the newly founded Ben and Catherine Ivy Center for Advanced Brain Tumor Treatment in Seattle, Washington). This research initiative aims to establish an effective means of increasing human brain cancer stem cell numbers in suspension bioreactors (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" 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 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 suggesting 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. Mark Basik (Clinical Surgeon/Oncologist at the Jewish General Hospital, McGill University, Montreal). This collaboration has involved the development of suspension bioreactor protocols for the expansion of breast epithelial stem cells (MESCs) and breast cancer stem cells (BrCSCs). The formation of breast tumors is thought to arise from mutations within the MESC population, which are then passed on to its progeny. The inherent longevity of MESCs increases their likelihood of exposure to potential carcinogenic agents and it is thought that mutations resulting from this exposure could adversely affect the ability of MESCs to control their proliferation. Gene expression profiling could therefore provide insights into potential therapeutic targets for breast cancer treatment. The scarcity of MESCs and their tumorigenic counterparts, however, hinder such investigations, which require large quantities of cells. This has provided the impetus to develop expansion protocols for suspension bioreactors using a serum-free medium.

(iv) Dr. Lawrence Rosenberg (Professor of Surgery and Medicine; Director, Division of Surgical Research, McGill University, and A.G. Thompson Chair of Surgical Research, McGill University Health Center, 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 (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 producing 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 mesenchymal stem cells (hMSCs) as an alternate approach in treating diabetes (Jung et al., 2011; Jung et al., 2010). 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 multiple sclerosis (MS).

Recent Publications

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