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.
|Facilitator / Guest||Topic|
Timothy Kieffer, Ph.D.
Professor, University of BC
|Course overview; the path from basic science to product development for cell based therapies|
Medical/Health Issues Reporter
The Vancouver Sun
|Responsible and effective communication of research to the public and interacting with the media|
Tim Caulfield, LL.B., LL.M.
Professor, Faculty of Law and School of Public Health, University of Alberta
|Ethical aspects of using stem cells and genetic engineering, stem cell tourism|
Knut Woltjen, Ph.D.
The Center for iPS Cell Research and Application (CiRA), Kyoto University
|The development of induced pluripotent stem cells and emerging tools for genome editing|
Peter Zandstra, Ph.D., FRSC
Chief Science Officer, Centre for the Commercialization of Regenerative Medicine (CCRM)
Professor, University of BC
Scaling things up; design of bioprocesses for the growth and differentiation of stem cells
An introduction to CCRM
Denis Claude Roy, Ph.D.
Professor, University of Montreal, CEO CellCAN Regenerative Medicine and Cell Therapy Network
|CellCAN: a network of Canada’s main cell therapy centres and description of the inner workings of GMP facilities for cell manufacturing|
Allan Eaves, M.D., Ph.D., FRCPC
Professor Emeritus, University of BC
President and CEO, STEMCELL Technologies, Vancouver
An introduction to the largest biotech company in Canada, focused on the supply of reagents for stem cell research
Michael Rudnicki, Ph.D., FRSC
Senior Scientist, Ottawa Hospital Research Institute, Scientific Director, Stem Cell Network (SCN), Ottawa
SCN: A network of more than 50 Canadian PIs and a catalyst for Canadian stem cell research
Megan Levings, Ph.D.
Investigator, BC Children’s Hospital Professor, Department of Surgery, University of BC
|Cell therapy to control immune homeostasis; from basic science to clinical trials|
James Shapiro, M.D., Ph.D., FRCSC
Professor, Department of Surgery, University of Alberta
|Clinical cell therapy for the treatment of diabetes and the view from a transplant recipient|
Cheryl Gregory- Evans, Ph.D.
Professor, Department Ophthalmology and Visual Sciences
University of BC
|Eye development and therapy for congenital eye disease|
Timothy Kieffer, Ph.D.
Professor, University of BC
|Course wrap up, student presentations, course evaluation|
- 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%
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.