MRM Insights: The MRM Network – where are we at and what’s next?
Every month, in MRM Insights, a member of the MRM Network is writing about stem cells and regenerative medicine from a different perspective. This month, Michel L. Tremblay, Professor in the Department of Biochemistry and at the Goodman Cancer Research Centre, Director of the MRM Network, gives us an overview of the McGill Regenerative Medicine Network.
The McGill Regenerative Medicine Network: where are we at and what’s next?
Dear colleagues and friends of the MRM,
It has been over two years now that the MRM was officially established at McGill. We worked diligently to move forward the “Commitments” that we stated in our strategic plan to the Faculty of Medicine and Health Sciences and that was approved by the Senate. I will be bold to write that together, we accomplished most of those commitments. Notably, a major part of our mission was to identify and to recognize investigators in the fields of Stem Cells and Regenerative Medicine (Reg. Med) across the University and from McGill Research Institutes. In the past two years, with our coordinator Dr. Marine Christin, we established and maintained our great website as well as being present on social media such as LinkedIn and Twitter. This survey notes that we have 113 principal investigators and with student and staff, over 570 members in the Network. This represent individuals from five different Faculties (Medicine and Health Sciences, Engineering, Science, Dentistry and Law) located in 25 different departments. We are also present with many active members in six McGill Research Institutes (MUHC, LDI/JGH, Neuro, Douglas, Shriners and added to this, the new Cancer Institute/GCRC).
We also contributed to other organisations promoting Stem cells and Reg. Med. in Canada. This includes the Canadian Stem Cell Network (SCN) for which we sponsored McGill PI applicants for their Project Grants program and by contributing travel/registration awards for graduate students and Post-Docs to attend the Till & McCulloch Meetings. As for ThéCell (Quebec FQRS network in Stem cells) we share many investigators in our activities and we have now agreed to organize and to launch a join partnerships project for the spring 2022. Our MRM community should be very proud of these accomplishments, as we have advanced the impact and visibility of our research and fulfilled the major goals that we had set in the strategic plan. Of course, the COVID pandemic took a great toll on our activities, yet we have maintained seminars, award competitions, developed a training program and more.
In the remaining section of this letter, I would like to address questions and interrogations that are for many of you still unclear on the past, current and future positioning of the MRM.
Why should McGill invest and consider Regenerative Medicine?
Using the National Institutes of Health definition “regenerative medicine is a process of creating living, functional tissues to repair or replace tissue or organ function lost due to age, disease, damage, or congenital defects”. We used it for our network because of the broader scope of activities that Reg. Med. influences in comparison to “stem cells”. Now that we understand what we are encompassing, a fair question to consider is why McGill should be present in this research field?
To provide a short answer to this interrogation we must first look at the scope and dynamic growth of this scientific area. At once, a simple answer would state that Reg. Med is directly concerned with aging and the plurality of ailments that are associated. Neuro degenerative diseases, damage cartilage and bone osteoporosis, general cachexia with the elderly, are just the tip of the iceberg of diseases that are targeted by Reg. Med research. But there are much more at stakes including a new field of commercial effort where Canada must have its university system engaged. A field that is growing rapidly and that it is already involved in all spheres of biomedical applications, beauty products, food consumption and more…
From the early days of stem cell manipulation in mammals, we have now a remarkable growth of multiple stem cell technologies and their use in basic and applied medicine. From 2010 to present the number of biomedical-related publications over this period increased by nearly 5% yearly. The numbers of journals dedicated to stem cells and regenerative medicine has also expanded, with all major publishers creating new journals (Cell – Stem Cell, Stem Cells, Stem Cells Reports and over 30 more titles). Yet, it is in the private sectors where we have seen the most important development. Stem Cells and Reg. Med companies have in the same period of 2010 to now, reached 9% growth in investment per year and it is still increasing. Like its major emergence into aerospace successes, the private sector has been extremely competitive and ingenious in investigating and advancing technologies using stem cells in the field of Reg. Med.. Based on a web monitoring group (i.e. BioPharmGuy), over 360 companies worldwide have entered this field, 38 of which are traded on the most important stock market NASDAQ, Tokyo, London…
The plethora of these new start-ups and major pharmaceuticals are engaged in generating a great diversity of human tissues, toward regenerations of skins, cartilage, bones, pancreatic cells, neurones, immune cells and blood products among others. In addition, it is also very attractive to esthetics, beauty and aging products with such targets as improving hair growth, wrinkles treatment, tooth replacement, and for the use of many other stem cells derived product that are also becoming the target of both academic and industrial research interests. Another measure of the headway that Stem Cell and Reg. Med are making is the rapid increase in clinical trial studies, with a recent tally of 160 clinical trials currently in progress worldwide.
Induced Pluripotent stem cells (IPSCs) or adult stem cells
With the clinical trials and commercialisation growth, a larger debate is now appearing in universities and companies. Which of the stem cells field will be the most productive and secured: IPSCs or their counterpart Adult Stem Cells. Since the publications of S. Yamanaka’ isolation of IPSCs, much has been written on their pluripotency and their ability to be used in the growth of a larger number of specific cell types. Two main issues are at the centre of this debate. The first is the necessity to induce their stemness using the four “Yamanaka factors” that include the transcription factors (Oct3/4, Sox2, Klf4, c-Myc) which must be introduce into primary differentiated cells. The second is the requirement to select and amplify the number of cells required for clinical interventions. The minimum of 30 or more generations creates a real risk of mutational changes that may provide growth advantages towards cell transformation and even metastatic properties to the donor cells. Hence, most IPSCs usages are for investigating patients’ cell phenotype, disease associated genetic changes and drug testing.
Adult stem cells in contrast are rare and represents undifferentiated cells embedded in all tissues. Since their intrinsic roles is to remain quiescent until normal cells of the tissue die, where they then divide and replace the missing cells. Currently, notwithstanding bone marrow transfer therapies, their usage is restraint as their isolation and growth is more difficult. Yet, as autologous therapeutics, they appear safer and the first choice as a source of donor cells for most of current clinical trials in stem cells.
Feeding the world
A surprising stem cell activity in the private sector is the development of lab grown meat. This expanding sphere of stem cell production is rapidly becoming an alternative to vegetarian food within the nascent field of “cellular agriculture”. For the most part several of those new biotech companies generate “clean meat” products by isolating and growing large quantity of IPSCs derived from tissues of cows, pigs, fish and others. Differentiated in muscle cells and by combining various cells into tissues, they become the bases of the new “clean meat industry”. Interestingly, public news reported that one of the best-known investors is notably Dr. Richard Klausner, the previous chief of the National Cancer Institute of the NIH. It is clear from this offshoot of IPSCs work that the field of food/bio engineering is of equal importance in this new business direction. IPSC, as an edible source of proteins follows existing sanitary rules and at that level, cell differentiation properties is an issue for the quality of the product and not in a putative carcinogenic risk from the genetic changes of IPSC. In these applications it is the industrialization and processing of the cell culture that is the concern. Industrial productions of vast number of cells, through >100 liters of bio-engineering cell cultures systems is a key factor for the profitability and larger consumption of such products by the public.
Canadian interest and world investment. Is this a thriving research field?
Taken together, scientific advances in the multiple fields of stem cells and their clinical applications, position Reg. Med as an important academic activity for decade to come. Indeed, this has been recognized by the Canadian government with past investments in the Canadian Stem Cell Network (SCN web site) of over $15 millions last fall and another $45 millions awarded to the SCN in the recent federal budget. These governmental decisions show that there are paths for funding in this field, and there is clearly a need for networks like the MRM to bring better visibility and resources to our young investigators in this expanding research endeavors.
This is however, a “drop in a big bucket” if we consider other G7 countries. In the US, Proposition 14 to fund state stem cell research was approved by California voters to the amount of $5.5 Billions for this state alone. In Japan, the central government is building a Reg. Med. Silicon Valley (Forbes magazine Jan 9, 2020) with over 388 billion yen ($3.88 billions) invested in companies as part of the “Innovation Hub Kyoto” with a majority of these being in wet lab research and regenerative medicine. Moreover, the establishment of an organization to promote stem technologies growth in Japan: the Forum for Innovative Regenerative Medicine (FIRM) has the mandate to provide to Japan and the world clinical grade IPSCs cells. The organisation’s mandate is clearly to promote Japan’s world most mature regenerative medicine ecosystems. The European community and the UK also produced enthusiastic reports in the urgent need for investment in these biomedical and industrial fields. As a summary of the growth of this field, a recent verified evaluation of this market that appear in Market Watch on April 26, 2021 evaluated the Global Regenerative Medicine Market at USD 19.10 Billion in 2018, expected to witness a growth of 22.72% from 2019-2026 and thus may reach USD 98.10 Billion by 2026.
Yet, one must also recognized many issues with the current situation, particularly that the number of clinical trials has yet to produce a larger acceptance in the clinics. Moreover, the lack of strict regulations led to many inappropriate uses of stem cells, which have clearly tarnished the clinical development and use of those technologies. (EASACFEAM Challenges and potential in regenerative medicine: a joint report from EASAC and FEAM. German National Academy of Sciences Leopoldina, Halle (Saale)2020. Date accessed: June 3, 2020. See article here).
Therefore, we can conclude that there is great potential, yet still many challenges to conquer. Among those: a better understanding of their dynamic and plasticity and the development of real pipelines, which is far to be established at McGill. This will also require novel medical and legal regulatory landscape and ethics guidelines, which was addressed by Cossu et al. for european community. (for more see Giulio Cossu, Robin Fears, George Griffin, Volker ter Meulen Regenerative medicine: challenges and opportunities www.thelancet.com Vol 395 June 6, 2020. See article here). Although the MRM has started to invest in ethics and public information on stem cells and regenerative Medicine, much remains to be done to position ourselves as a source of unbiased and scientifically sound information for the general population.
What about us at McGill? Are we up to the challenge?
Nearly 6 years ago, several researchers at McGill were anxious that, in Canada, the main efforts were centralized towards few universities and while McGill U had significant research endeavors in this field, it was nevertheless poorly represented in these important organizations. This led to the proposal to create the MRM Network. To carry this mandate, the MRM received in March 2019 a 5-year recurrent budget from the Faculty of Medicine and Health Sciences, an important support by the Strauss foundation and a generous philanthropic gift from a donor, Mme Besner. Of great importance, it was decided that the MRM will be open to any stem cell and regenerative medicine researchers (Graduate students to PIs) from all Faculties at McGill and affiliated institutions.
Where do we go from here?
The creation of the MRM Network has started a recognition by McGill that a first-rate world university like ours should be at least examining what we are already doing and support those of our faculty members that are increasingly attracted by this biomedical and increasingly societal pursuit. This first step is done and, from our point of view, there are no choice but being involved in this academic development. What should we look forward at the end of our five years’ mandate?
For me, the logical step would be to employ our remaining three years of commitments to create, as most top 100 universities in the world have done, a first McGill Centre in Regenerative Medicine. This will ensure a solid ground to expand the goals that we undertook in the initial strategic plan. It would crystallize our efforts to give to the McGill Regenerative Medicine community and administrative infrastructure and the financial resources required to the long-term sustainability of this academic research. Moreover, this will allow the MRM community to mature and to examine in due time the possibility of expanding into an Institute. This is a path that led last year to the establishment by the senate of the McGill Cancer Institute.
I conclude this letter by inviting you to provide us at the MRM, with your ideas on how we should develop the next stage of our growth. Our coordinator Dr. Marine Christin or myself will welcome your suggestions and comments at email@example.com.
With these last words, I also wanted to thank all of our colleagues that participated to our committees and activities. It is their collective effort that make the MRM a dynamic organization for the development of Reg. Med. at McGill. Do not hesitate to contact us, we are always welcoming your participation.
Michel L. Tremblay.