By Samantha Yammine, PhD Candidate in Derek van der Kooy’s lab at the University of Toronto. See tweets live from #TMM2016 via @SamanthaZY here.
Last week, 430 Canadian scientists, trainees, industry professionals, science communicators and international guests gathered in the picturesque ski town of Whistler, British Columbia for the annual Till & McCulloch meeting (TMM). This is Canada’s premier conference for stem cell research, which is co-hosted by the Centre for Commercialization of Regenerative Medicine, the Stem Cell Network, and the Ontario Institute for Regenerative Medicine.
The conference is named for Drs. James Till and Ernest McCulloch, two Canadian scientists who were among the first to describe stem cells back in 1961, which sparked a continuing legacy of cutting edge stem cell research in Canada. Many of the talks were about the exciting new stem cell research in Canada from the labs of Molly Shoichet, Jeff Biernaskie, Derek van der Kooy, Andras Nagy, Fabio Rossi, Janet Rossant, Freda Miller, Michel Cayouette and Steve Scherer.
But the strength of this conference was the diversity of its speakers and their interdisciplinary approaches to stem cell biology and regenerative medicine. Even a seemingly narrow topic like “stem cells” contains a huge breadth of research, which the 2016 TMM did an excellent job of covering in just 2.5 days through a variety of different lenses. I’m sharing highlights of these different lenses through which we can view stem cell biology below.
1) Biological Computation:
The conference started early morning on Monday October 24th with a look at stem cell biology through the eyes of Microsoft Research Scientist Sara-Jane Dunn. In collaboration with Austin Smith’s lab, she studies how biological computation can allow us to better define predictive networks of interactions between cells and signaling pathways within cells. Her team has built RE:IN – Reasoning Engine for Interactive Networks – the first version of an accessible online tool that can be used to study constraints within biological networks and identify, “the simplest model that can explain observations.”
2) Chemistry & engineering:
Later that same day we heard from Aaron Wheeler of the Department of Chemistry at U of T, who shared with us the updates and future avenues for his “lab on a chip” digital microfluidics technology. This tube-free system offers the opportunity to do high throughput experiments all on a tiny chip with a hydrophobic surface and electrostatic forces moving around fluids in an automated fashion instead of tired hands and pipettes. They are sparking up a collaborative project with Cindi Morshead’s lab to study neural stem cells in this platform, and are also looking to optimize their microfluidics for single cell analyses, which will be incredibly coveted given the current boom in single cell -omics.
Another interesting techniques-based talk came from chemical engineer Alison McGuigan. She presented her lab’s cleverly simple approach to studying 3D microenvironments in a tractable manner: Tissue Roll for Analysis of Cellular Environment and Response (TRACER). You culture the cells in a rolled up scaffold so they can interact 3 dimensionally, but then unroll them for ease of analysis while retaining tractability of which cells were interacting in the 3D conformation. While initially designed with tumour microenvironments in mind, this could be a nice future in vitro approach to study ways the niche can regulate stem cells.
3) Biotech entrepreneurship:
An additional approach to studying things in 3D came from the Chief Scientific Officer of the startup Aspect Biosystems, Sam Wadsworth. After an amazing start to his talk by taking a group selfie in the style of Ellen Degeneres à la Oscars 2014, Sam told us about the startup he co-found based on 3D bioprinting and tissue engineering technology. Their goal is deliver a rapid technique for printing cells, including those derived from stem cells, into 3D structures for drug screening and – eventually – tissue transplantation.
— Aspect Biosystems (@aspectbiosys) October 25, 2016
Group selfie by CSO of Aspect Biosystems, Sam Wadsworth. (MIA: ⅓ of audience on the left)
4) Clinical applications:
On the topic of using stem cells in the clinic, invited guest Masayo Takahashi from RIKEN in Japan talked about her clinical trials for macular degeneration in collaboration with Nobel Prize winner Shinya Yamanaka. Her group led the first clinical trial transplanting induced pluripotent stem cell (iPSC)-derived retinal pigmented epithelium to a patient with macular degeneration in 2014, an important study whose success she raved about. Echoing previous coverage on this blog, she reports no tumour formation in that study and that their current protocol continues to be robust such that no tumours form even with the small genetic changes that accumulate overtime. While this trial was on hold as previously mentioned here, it has now been resumed and they are set to go forth trying transplantation of allogeneic tissue after success with HLA-matched transplantation in monkeys.
Masayo ended sharing some inspiring words including:
“People said: ‘the central nervous system will never regenerate.’
I said: ‘they just don’t know about stem cells.’
Others said: ‘the retina is too complicated to regenerate.’
I say: ‘they don’t understand the needs of the patient.’”
It was a valid point that, particularly in the case of vision, a 100% recovery is not needed to significantly improve a patient’s quality of life.
5) Clinical success – patient perspective:
We also heard from Lauralyn McIntryre about her phase I clinical trial to use mesenchymal stem cells to treat septic shock, which is in collaboration with MD Duncan Stewart and has been summarized well here and here. This work is being conducted at the Ottawa Hospital in Canada, where another stem cell-based clinical trial also met great success, which we had the pleasure of learning about directly from the second patient in the trial, Tina Ceroni.
Tina told her incredibly honest and difficult story about being diagnosed with Stiff Person Syndrome when she was 28 years old, a debilitating disease with a few treatment strategies but real cure. She was patient number two in a clinical trial by Dr. Atkins at the Ottawa Hospital where she received several rounds of aggressive chemotherapy and drug therapy, then transplantation of her own blood and bone-marrow derived stem cells back in to reboot her immune system. Four years later and she was standing on the stage, looking as normal as anyone, in remission and symptom-free.
Tina said, “stem cell transplant has the hope to change the life for so many, and often hope is the only medicine we have. But it is important to inform the public [about stem cell research] in ways that is safe, effective, and ethical.” She is now an advocate for stem cell research and bone marrow transplant, and helps fundraise to propel research forward through her organization, Share a Cell.
It is especially important to highlight that even though Tina knows firsthand how important it is to get stem cells in the clinic, she still advocates for research first to make sure those therapies are safe and ethical by the time they get to patients. This is increasingly important for stem cell researchers and communicators to keep in mind, and one of the posters from a student in Tim Caulfield’s group highlighted this through their new study showing far too many naturopath clinics in North America offering unregulated “stem cell” therapies for a variety of different cosmetic and life-threatening ailments.
6) Regulatory law & ethics:
The last unique lens to consider stem cell research through came in the form of we heard an interesting talk from bioethicist Insoo Hyun from Case Western University about how bioethics and regulations do not try to slow down research but rather lay the foundation for it to continue.
He shared with us the interesting history of the 14 day “rule” for studying human embryos in vitro – that no live human embryo can be kept alive beyond 14 days post-fertilization if not implanted in a woman, which first surfaced in 1979 and has surfaced in many different versions around the world since. Interestingly, this is “rule” is only encoded in law in a few countries, including Canada, Australia, and New Zealand. In countries like the US, China, Japan, and India it is only specified in guidelines but not actually encoded or enforced legally.
I keep putting rule in quotation marks because he emphasized the point that this “rule” should really be viewed more as a public policy tool — it is less of a moral distinction and aims to include as much diverse opinion as possible. He promised that policy can change, but that we should always consider 1) what experiments the current guidelines prohibit; 2) why those experiments are important; 3) what the alternative guideline would be.
The biggest lesson
Contrary to what the length of this post might suggest, I’ve really only scratched the surface of the quality research and interdisciplinary insights shared at the 2016 TMM.
For me, the biggest take-away was how important it is to remain open-minded and collaborative — to attend the talk by the computer scientist or chemist that you would normally run scared from. Only an open mind will be receptive enough to recognize the next breakthrough when it is cloaked in uncertainty.
There were two final speakers I’d like to mention that exemplify this well. The first is Nika Shakiba, a PhD candidate from Peter Zandstra’s bioengineering lab. Nika presented her research using genetic barcoding strategies to monitor the heterogeneity of cells during the reprogramming process. Nika found that instead of being a mix of all starting cells, populations of reprogrammed cells actually become dominated by a couple of clones derived from only a few of the starting cells. Being a biomedical engineer with strong computational and mathematical competencies, Nika modeled in silico what her cell populations would look like if the takeover were stochastic and found evidence favouring a more deterministic model. She argues that not all cells undergo reprogramming equivalently, contrary to popular belief that any cell will reprogram if you wait long enough.
Dogma was challenged again in Connie Eaves’ talk, where she wrote out a list of assumptions we once had about blood stem cells, then highlighted some of her research that pokes holes in those assumptions. One example was the previous notion that all blood stem cells are heterogeneous, which her lab has shown is not true based on proteomic approaches, and others have also observed.
Given that stem cell biology and regenerative medicine are so inherently multidisciplinary, the biggest breakthroughs only seem imminent in a future where scientists work collaboratively with each other but also external stakeholders such as policy-makers, private industry, and patients. Studying stem cells through computational, engineering, biotech, clinical, ethical and legal lenses is thus imperative for gaining a realistic understanding of the hope this research holds for understanding development and homeostasis, and translating this knowledge to regenerative medicine.