Chemical & Petroleum Engineering

Leo A. BehieLeo A. Behie

Professor

Canada Research Chair (CRC)
in BioMedical Engineering

Director of the Pharmaceutical Production Research Facility (PPRF)

P.Eng.

Fellow
Chemical Institute of Canada (CIC)
  • Room: EN B204B
  • Telephone: (403) 220-6692
  • Fax: (403) 284-4852
  • E-mail: behie@ucalgary.ca
B.E.Sc. 1968
M.E.Sc. 1969
Ph.D. 1972 (University of Western Ontario)
NATO Postdoctoral Fellowship 1973 (University of Cambridge, England)

Awards / Accolades

DR BEHIE'S research expertise is in chemical reaction engineering as applied in a number of areas including biomedical and tissue engineering and multiphase chemical reactors.

Although these areas appear to be unrelated, the common link that ties them together is new reactor technology. 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 embryonic stem cells (hESC) and human adult stem cells [i.e. neural stem cells (NSC), mammary epithelial stem cells (MESC), breast and brain cancer stem cells (CSC), pancreatic progenitor cells and liver stem cells].

In July 2001, Dr. Behie became a Principal Investigator in the Stem Cell Network (www.stemcellnetwork.ca), a Canadian Network of Centers of Excellence (NCE). Through this network, he is presently collaborating with -

(i) Dr. Ivar Mendez (a neurosurgeon and Director of the Neural Transplantation 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 an animal model has been ongoing for 2 years targeting the design of clinical trials for the treatment of Parkinson's disease. In other words, PPRF researchers have grown human brain tissue (i.e. neural stem/progenitor cells) in large-scale bioreactors, an important step that may lead to the transplantation of stem cells 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. The objective of the first project was to co-graft bioreactor-expanded human neural precursor cells [Mukhida et al. (2006)] which yielded very important results, namely, an enhanced survival of dopaminergic neurons and a significantly improved behavioural recovery in an animal model of Parkinson's disease. The second successful project involved the transplantation of pre-differentiated bioreactor-expanded human telenencephalic neural stem cells into a rodent model of Huntington's disease (McLeod et al. 2006). The important conclusion from this work was that the transplants proved to an effective treatment in this preclinical study of Huntington's disease, opening the door for proceeding to human clinical trials.

(ii) Dr. Peter Dirks (a neurosurgeon at the Sick Children's Hospital in Toronto). This research initiative aims to establish an effective means of increasing human brain cancer stem cell numbers in suspension bioreactors. Recent evidence suggests that normal neural stem cells can undergo 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. 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. This, in particular, has become a significant impediment to the ability of the Stem Cell Network's Cancer Stem Cell Genomics and Therapeutics Core Project to discover therapeutic targets for human brain cancer stem cells through high throughput drug screening.

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 basis for investigating brain cancer stem cell expansion. Furthermore, the expertise of Dr. Dirks' laboratory in characterizing and purifying human brain cancer stem cells derived from several types of brain tumors, shall ensure that the process developed will result in the expansion of cancer stem cells, rather than their progenitors.

(ii) Dr. Mark Basik (Clinical Surgeon/Oncologist at the Jewish General Hospital, McGill University, Montreal) and Dr. John A. Hassell (Director of the Center for Functional Genomics and Professor of Biochemistry at McMaster University, Hamilton) on the development of suspension bioreactor protocols for the expansion of newly discovered breast epithelial stem cells (MESCs). 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 tumourgenic 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. Recent work in our laboratory (Youn et al., 2005) has successfully shown the expansion of undifferentiated MESCs as tissue aggregates in bioreactors. The development of suspension bioreactor protocols and MESC medium have allowed for the scaled-up production of these cells, addressing the issue of MESC scarcity.

And finally, through a newly funded CIHR Regenerative Medicine Application, a strong collaboration has been established with 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). One objective will be to further extend our work on expanding a newly discovered population of pancreatic progenitor cells that may be used to treat Type 1 diabetes (Bodnar et al., 2006). Recently, Dr. Behie and his colleagues at PPRF successfully produced porcine islet-like tissue in a suspension culture bioreactor (Chawla et al., 2006). 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 technologies to producing new human pancreatic islets for the treatment of Type 1 diabetes using the world-famous "Edmonton Protocol".

Selected Publications