Stem Cells and Regenerative Medicine: What does the Future Hold?
Regenerative Medicine has the potential to revolutionize medical practice, with cell therapy emerging as a powerful treatment option for a variety of debilitating diseases. This course will introduce students to the promises but also the challenges that lie ahead in realizing this potential.
Canadians Jim Till and Ernest McCulloch had a pivotal role in the history of stem cell science, being the first researchers to prove the existence of stem cells in the 1960s. Stem cells have the remarkable potential to develop into many different cell types in the body during early life and growth. In addition, in many tissues they serve as an internal repair system, dividing essentially without limit to replenish other cells as needed. When a stem cell divides, each new cell has the potential to either remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, a brain cell, or an insulin producing cell.
Today, donated organs and tissues are often used to replace ailing or destroyed tissue, but the need for transplantable tissues and organs far outweighs the available supply. Stem cells, directed to differentiate into specific cell types, offer the possibility of a renewable source of replacement cells and tissues to treat diseases including macular degeneration, spinal cord injury, stroke, burns, heart disease, diabetes, and arthritis.
In 1998, scientists developed methods to isolate embryonic stem cells from fertilized human embryos. The embryos used in these studies were created for reproductive purposes through in vitro fertilization procedures. When they were no longer needed for that purpose, they were donated for research with the informed consent of the donors. The embryonic stem cells derived from these embryos have the capacity for virtually unlimited cell division, but also the differentiation into all of the >200 cell types that make up the human body, thereby possessing tremendous therapeutic potential. The Food and Drug Administration (FDA) approved the first clinical trial in the United States involving human embryonic stem cells in 2009 for the treatment of spinal cord injury. Other trials have since been approved for eye disease and diabetes. However, much work remains to be done in the laboratory and the clinic to understand how to effectively use these cells for cell-based therapies to treat disease, which is also referred to as regenerative medicine.
Despite their promise, there are ongoing ethical debates regarding the derivation and use of embryonic stem cells. A major advance came in 2006, when Japanese scientists developed tools to make stem cells from adult cells, such as can be readily obtained from skin or blood. These “induced pluripotent stem cells” are adult cells that have been genetically reprogrammed to an embryonic stem cell-like state by being forced to express genes and factors important for maintaining the defining properties of embryonic stem cells. Aside from eliminating the ethical concerns associated with using cells derived from human embryos, these cells have the advantage of being perfectly matched to patients and thus not stimulating an immune response when transplanted. In 2012, Professor Shinya Yamanaka received the Nobel Prize in Medicine for this ground-breaking research.
Aside from use as potential therapies, human stem cells are being used widely to model diseases and thereby reduce the use of animals for experimentation. Techniques are being developed to differentiate stem cells into miniature human organs. An organ-on-a-chip is a multi-channel 3-D microfluidic cell culture chip that simulates the activities, mechanics and physiological response of entire organs. Researchers are working towards building a multi-channel 3D microfluidic cell culture system in which several 3D cellular aggregates of multiple cell types are cultured to mimic multiple organs in the body, a so-called human-on-a-chip. Such systems may be very useful for drug testing, and to potentially measure direct effects of one organ’s reaction on another. For instance, test substances could be screened to confirm that even though they may benefit one cell type, they do not compromise the functions of others. Such studies may improve the likelihood that new drugs pass clinical trials.
A limitation of using induced pluripotent stem cells for therapy is the potential that they harbor one or more genetic mutations that contribute to disease onset. This can now be addressed with powerful new genetic engineering approaches that are rapidly gaining widespread adoption, such as “CRISPR”. CRISPR-Cas9 is a genome editing tool that is creating a buzz in the science world. The system consists of two key molecules that combine to introduce a change into the DNA. The enzyme Cas9 acts as a pair of ‘molecular scissors’ to cut the two strands of DNA at a specific location in the genome so that bits of DNA can then be added or removed. A pre-designed piece of RNA called guide RNA (gRNA), with RNA bases that are complementary to those of the target DNA sequence in the genome, ‘guides’ Cas9 to the right part of the genome. This ensures that the Cas9 enzyme cuts at the desired point. The cell recognizes that the DNA is damaged and tries to repair it, at which point strategic changes to one or more genes can be made. The combination of stem cells and genome editing is a very powerful and exciting approach for disease modeling and therapy.
With the successes also comes hype and false promises. There have been many grim stories about the abuse of regenerative medicine and stem cell therapies in the headlines. Hundreds of international stem cell clinics now hawk unproven, unregulated therapies to desperate people. Such “stem cell tourism” often does more harm than good, detracting from the positive forward motion of regenerative medicine and the very real potential for individual patients and the national economy.
The next wave of regenerative medicine research is tackling enormous health care issues: AIDS, Alzheimer’s disease, diabetes, heart disease, blood cancers, and blindness, among others. Despite the complexities, regenerative medicine, which encompasses stem cell research, tissue engineering, and gene therapy, has the potential to positively affect many clinical areas. Academic institutions and responsible companies are working hard to unlock the potentially transformative impact of stem cells. It is timely to introduce a graduate level course at UBC to engage both students and the public with reliable information on the current status of regenerative medicine and look to the future possibilities. The course will also likely catalyze new initiatives and collaboration with UBC scientists.
The students will be exposed to the tools and techniques involved in developing cell based therapies for disease, the hurdles that need to be overcome and the processes that need to be followed to develop a product, including the path through pre-clinical and clinical trials, and the costs involved along the way. Ten faculty and a medical reporter have agreed to participate in the course, including 5 external faculty who will share their perspectives on the successes and failures, and experience from bench to bedside. Ethical issues will be discussed, along with examples of misplaced hype and false promises. The role of academia and industry will be discussed, along with the role of funding from government and charitable organizations. Students will finish the course with a greater understanding of the vast potential of stem cells and genetic engineering, the complexities of the field, and an appreciation of Canada’s contributions in this fast-moving field.
PHYL 548B 002
Advanced Topics in Human Physiology: Stem Cells and Regenerative Medicine: What does the Future Hold?
Supported by Killam Connection Program
Timothy J. Kieffer, PhD
Professor, Department of Cellular & Physiological Sciences
Life Sciences Centre Room LSC1330
Wednesdays, 2018 Term 2 (Jan 3, 2018 to Apr 4, 2018)
13:00 to 16:00
This course will be comprised of 12 scheduled weekly classes, each 3 hours in length, plus 5 evening public lectures, for a total of ~41 hours
All classes will be held in Life Sciences Centre Room LSC1330, 2350 Health Sciences Mall, UBC. All public lectures will occur in the Life Sciences Centre.
There will be no pre-requisites for this course.
Students must bring a laptop computer to class for on-the-fly web searches.
Relevant reading material will be assigned and made available on the course website. No textbooks will be used.
- Understand the path and recognize the challenges of developing a cell-based therapy
- Critique the hype and unsubstantiated claims in regenerative medicine
- Report on public lectures via a blog post on course website
- Appraise and interpret research publications of guest faculty
- Achieve a professional (informed scholarly) identity while interfacing with the public
- Complete and present a synopsis of a biotechnology company in the stem cell field
Mode of Assessment
- Class and public lecture participation 20%
- Class presentations / debates 20%
- Online blog posting and editorial position statements, website content 30%
- Final class assignment 20%
- Assessment from peers 10%
|Facilitator / Guest||Topic|
Timothy Kieffer, Ph.D.
Professor, University of BC
Wed Jan 3, 2018 (1-4PM)
Course overview; the path from basic science to product development for cell based therapies
Medical/Health Issues Reporter
The Vancouver Sun
Wed Jan 10, 2018 (1:30-4:30PM)
Responsible and effective communication of research to the public and interacting with the media
James Shapiro, M.D., Ph.D., FRCSC
Professor, Department of Surgery, University of Alberta
Wed Jan 17, 2018 (1-4PM)
Clinical cell therapy for the treatment of diabetes and the view from a transplant recipient
*plus public lecture Jan 17 (7-8PM)
Allen Eaves, M.D., Ph.D., FRCPC
Professor Emeritus, University of BC
President and CEO, STEMCELL Technologies, Vancouver
Terry Thomas, PhD
Chief Scientific Officer, STEMCELL Technologies
Wed Jan 24, 2018 (1-4PM)
An introduction to the largest biotech company in Canada, focused on the supply of reagents for stem cell research
Denis Claude Roy, Ph.D.
Professor, University of Montreal, CEO CellCAN Regenerative Medicine and Cell Therapy Network
Wed Jan 31, 2018 (1-4PM)
CellCAN: a network of Canada’s main cell therapy centres and description of the inner workings of GMP facilities for cell manufacturing
*plus public lecture Jan 31 (7-8PM)
Peter Zandstra, Ph.D., FRSC
Chief Science Officer, Centre for the Commercialization of Regenerative Medicine (CCRM)
Professor, University of BC
Wed Feb 7, 2018 (1-4PM)
Scaling things up; design of bioprocesses for the growth and differentiation of stem cells
An introduction to CCRM
Michael Rudnicki, Ph.D., FRSC
Senior Scientist, Ottawa Hospital Research Institute, Scientific Director, Stem Cell Network (SCN), Ottawa
Wed Feb 28, 2018 (1-4PM)
SCN: A network of more than 50 Canadian PIs and a catalyst for Canadian stem cell research
*plus public lecture Feb 28 (7-8PM)
Megan Levings, Ph.D.
Investigator, BC Children’s Hospital Professor, Department of Surgery, University of BC
Wed Mar 7, 2018 (1-4PM)
Cell therapy to control immune homeostasis; from basic science to clinical trials
Timothy Caulfield, LL.B., LL.M.
Professor, Faculty of Law and School of Public Health, University of Alberta
Thur Mar 15, 2018 (1-4PM)
Ethical aspects of using stem cells and genetic engineering, stem cell tourism
*plus public lecture Mar 15 (7-8PM)
Cheryl Gregory- Evans, Ph.D.
Professor, Department Ophthalmology and Visual Sciences
University of BC
Wed Mar 21, 2018 (1-4PM)
Eye development and therapy for congenital eye disease
Knut Woltjen, Ph.D.
The Center for iPS Cell Research and Application (CiRA), Kyoto University
Wed Mar 28, 2018 (1-4PM)
The development of induced pluripotent stem cells and emerging tools for genome editing
*plus public lecture Thur Mar 29 (7-8PM)
Timothy Kieffer, Ph.D.
Professor, University of BC
Wed Apr 4, 2018 (1-4PM)
Course wrap up, student presentations, course evaluation
Timothy Caulfield, LL.B., LL.M.
Professor, Faculty of Law and School of Public Health,
University of Alberta,
Timothy Caulfield is a Canada Research Chair in Health Law and Policy, a Professor in the Faculty of Law and the School of Public Health at the University of Alberta and Research Director of the Health Law Institute at the University of Alberta. Over the past several years he has been involved in a variety of interdisciplinary research endeavours that have allowed him to publish over 300 academic articles. He is a Fellow of the Trudeau Foundation and the Principal Investigator for a number of large interdisciplinary projects that explore the ethical, legal and health policy issues associated with a range of topics, including stem cell research, genetics, patient safety, the prevention of chronic disease, obesity policy, the commercialization of research, complementary and alternative medicine and access to health care. Professor Caulfield is and has been involved with a number of national and international policy and research ethics committees. He has won numerous academic awards and is a Fellow of the Royal Society of Canada and the Canadian Academy of Health Sciences. He writes frequently for the popular press and is the author of two recent national bestsellers: The Cure for Everything: Untangling the Twisted Messages about Health, Fitness and Happiness (Penguin 2012) and Is Gwyneth Paltrow Wrong About Everything?: When Celebrity Culture and Science Clash (Penguin 2015).
Knut Woltjen, Ph. D.
Center for iPS Cell Research and Application
Dr. Woltjen obtained his B.Sc. Honors in Molecular Genetics from the University of Alberta (1998), and his Ph.D. in Biochemistry. and Molecular Biology (2006) from the University of Calgary, where he developed a gene-targeting vector construction method by recombination. During a postdoctoral fellowship in Medical Genetics in Toronto, he employed the piggyBac transposon in a novel approach to create induced pluripotent stem cell (iPS) cells, and served as Manager of the Ontario Human iPS Cell Facility. Dr. Woltjen joined Kyoto University’s Center for iPS Cell Research and Application (CiRA) in 2010, and in 2013 was cross-appointed to Kyoto University’s Hakubi Center for Advanced Research as an Associate Professor. Dr. Woltjen employs programmable nucleases in human iPS cells to study genetic variation in development and disease.
James Shapiro, M.D., Ph.D., FRCSC
Professor, Department of Surgery
University of Alberta
James Shapiro was born in Leeds, England, son of a family doctor. He studied Medicine in Newcastle and trained in Surgery in Bristol. He developed a longstanding interest in islet transplantation as a medical student. He has been on Faculty at the University of Alberta since 1998, where he now holds the Canada Research Chair in Transplantation Surgery and Regenerative Medicine. He directs the living donor liver transplant and the islet transplant programs in Edmonton. He was the lead investigator on the famous “Edmonton Protocol” cell transplant treatment for diabetes.
He is the Project 1 lead for the CNTRP, which is actively researching ex vivo organ transplant repair. In 2016, James and his team began first in human trials with embryonic stem cell derived insulin producing cells transplanted in an immunoisolation device, in partnership with ViaCyte Inc. James is the recipient of a Hunterian Medal from the Royal College of Surgeons of England, the Gold Medal in Surgery, is a Fellow of the Royal Society of Canada and a Fellow of the Canadian Academy of Health Sciences.
Denis Claude Roy, Ph.D.
Professor, University of Montreal
CEO, CellCAN Regenerative Medicine and Cell Therapy Network
Renowned researcher in hematopoietic stem cell transplant and executive committee member of the Canadian National Cancer Institute, Dr. Roy is Director of the Cellular Therapy Laboratory, scientific director at MRH and full professor at the Faculty of Medicine of the University of Montreal. He is also member of a working group on acute leukemia stem cell transplant, member of the Canadian Blood and Marrow Transplant Group and Clinical Trials and member of the Canadian Network on stem cell research. Dr. Roy did a postdoctoral fellowship in tumor immunology at the Dana-Farber Cancer Institute at Harvard University, USA and did his medical doctorate at University of Montreal. The aims of the studies performed at the laboratory are to use cellular and immunological approaches to fight such blood cancers as leukemia and lymphoma. The research unit is examining different monoclonal antibodies and immunoconjugates as well as a photodynamic approach for eliminating cancerous and alloreactive cells. The laboratory has also developed particular expertise in translational research, enabling the transfer of basic discoveries to patients. New hematological and immunological strategies have been identified and were implemented in early clinical studies (Phase 1 and 2). Dr. Roy’s laboratory is also the principal investigator of a multicentric study (Canada and USA) to evaluate a new photodynamic treatment. Dr. Roy is also working on the expansion of hematopoietic stem cells and blood cell progenitors that will enable and accelerate hematological and immunological reconstitution following transplantation. Dr. Roy is Kiadis Pharma’s (Netherlands) leading academic partner for the development of its blood cancer products and has collaborated with Kiadis Pharma for many years. Dr. Roy significantly contributed to the development of all ATIR™ blood cancer products, Reviroc™ and Rhitol™.
Michael Rudnicki, OC, Ph.D., FRSC
Senior Scientist, Ottawa Hospital Research Institute
Scientific Director, Stem Cell Network (SCN)
Dr. Michael Rudnicki is a Senior Scientist and the Director of the Regenerative Medicine Program and the Sprott Centre for Stem Cell Research at the Ottawa Hospital Research Institute. He is Professor in the Department of Medicine at the University of Ottawa. Dr. Rudnicki is CEO and Scientific Director of the Canadian Stem Cell Network (SCN). Dr. Rudnicki’s achievements have been recognized by numerous honours including being named a Tier 1 Canada Research Chair, an International Research Scholar of the Howard Hughes Medical Institute for two consecutive terms, a Fellow of the Royal Society of Canada, and an Officer of the Order of Canada.
Dr. Rudnicki is an internationally recognized thought leader in molecular genetics and regenerative medicine whose research has transformed our understanding of muscle development and regeneration, and fueled the development of novel molecular and stem cell based approaches to the treatment of muscular dystrophy and other neuromuscular disorders. Dr. Rudnicki’s key discovery was the identification and characterization of muscle stem cells. This work pivoted the field towards the study of adult regenerative myogenesis and set the stage for novel molecular and stem cell based approaches to the treatment of muscular dystrophy and other neuromuscular disorders. Dr. Rudnicki is a member of the editorial boards of Cell Stem Cell, Journal of Cell Biology, and Stem Cells. He is a founding Co-Editor-in-Chief of the journal Skeletal Muscle. Dr, Rudnicki has also organized many international research conferences and was a founding director of the Society for Muscle Biology.
For the past 12 years, Dr. Rudnicki has led the Stem Cell Network (SCN), a transformative initiative involving over 150 investigators across Canada, with a mandate to catalyze the translation of stem cell research into clinical applications, commercial products and public policy. As Scientific Director of the SCN, he has forged a national community that transformed stem cell research in Canada and brought research to the point where regenerative medicine is impacting clinical practice.