Keys to successful stem cell translation – Nurses, physicians and patient advocates

By Heather Main

I recently attended the UCSD Health CIRM Alpha Stem Cell Clinics Network Symposium at the Sanford Consortium, San Diego.

There was of course some great academic research presented, including conflicting views on liver stem cell compartments from Roel Nusse and David Brenner, and advances in CRISPR technologies from Matthew Porteus. However, what struck me about this meeting was how well it presented patient need and churned emotions outside the normal excitement or skepticism of an academic/basic science conference.

Shirley Johnson is a name I have never heard before and while my mother is in fact a nurse, listening to Shirley made me realise how I don’t even know what my mum does when she goes to work let alone what a nurse trained in clinical trials and/or cellular therapies would do.  Shirley presented how the City of Hope hospital has incorporated its alpha clinic into its day surgery, ‘in the trenches’ with the nurses instead of ‘in the ivory tower’ with the clinical research unit. How alpha clinics are dependent on the knowledge, skills, abilities and behaviours of nurses, who drive the patient experience and form the link between the doctors/researchers and patients. I left this talk with great respect for these alpha clinic nurses and a desire to call my mum.Axis Advocacy

Another great talk was from Steve Cramer, a dynamic, witty fellow describing his everyday experiences and frustrations in providing treatments to his stroke patients. He outlined the importance of rigourous pre-clinical data (Ann Neurol. 2006 Mar;59(3):467-77.1,026 experimental treatments in acute stroke. O’Collins VE1, Macleod MR, Donnan GA, Horky LL, van der Worp BH, Howells DW.) and non-linear thinking that should allow promising treatments in the absence of a mechanism of action (Neurology. 2014 Apr 8; 82(14): 1277–1286. Meta-analysis of preclinical studies of mesenchymal stromal cells for ischemic stroke Quynh Vu, BS,* Kate Xie, BA,* Mark Eckert, PhD, Weian Zhao, PhD, and Steven C. Cramer, MD). Steve was both comical and desperately serious, describing how his patients do not live in boxes with controlled environments and diets, have diverse genetic backgrounds, have non-stroke related health issues, bills to pay, immigration issues, 1/3 suffer from depression, that we will not know how treatments fare in humans until we try it in them. People like Steve are great to remind us that humans are not lab animals, that invasive procedures incur risk, that patients die from infections due to immunosuppression, that clinical trials need to be well organised and stratified to ensure benefits are not diluted in human variance.

Adrienne Bell-CorsThe final talk of the day was from Adrienne Bell-Cors, founder of Axis Advocacy and the 4th mother in her family to have a child affected with sickle cell anaemia. Adrienne’s talk drove home the importance of advocates for not only supporting patients and their families but in dispersing information about science and driving research and translation through raising funds and assisting in development and approval of clinical trials towards market delivery. Cheap science is bad science she says.

As Sickle Cell Anemia is particularly prevalent in the African American community it was disturbing to be reminded of the troubles with access to good healthcare that this community has faced in recent history, that Adrienne was the first woman in her family to undergo natural menopause rather than forced sterilisation or ‘recommended’ hysterectomy before 25 years of age. The women before her were either force sterilised or ‘recommended’ by doctors to have hysterectomies before the age of 25.  The history of treatment of this community makes it difficult for the patients and their families to trust medical professionals, explaining why they are not lining up to participate in clinical trials. The role of patient advocates in being cultural advisors to researchers is something that never occurred to me with such intensity.

This meeting was a demonstration of the great job CIRM is doing to recognise the importance of the patient in research translation. The advances already in CIRM funded clinical trials through alpha clinic trials is remarkable and sheds light on the future of our field.

First impressions of the US stem cell environment from an Aussie

Heather_MainBy Heather Main

I moved to the San Diego from Australia in August 2015, and Paul asked me if I could write something on my first impressions of doing science in the US, as opposed to other countries I have worked/studied in (Australia, Scotland, Sweden and Singapore).

If you look at the land size of Australia and consider that we have only 7% of the US population you will understand directly that funding and collaborative opportunities are not as easy to find. There’s probably little collaborative advantage in the US compared to Europe, which has over double the number of people as the US and only 3% larger land mass. In defense of Australia we punch above our weight, with the first stem cell company (Stem Cell Sciences) and currently the world’s largest (Mesoblast) originating there…even Viacyte has Australian origins.

It seems like it is hard not to be political here in the US….I guess I have arrived at a special time, but after working in Sweden for 5 years and living through gun control regulation following the 1996 Port Arthur massacre in Australia, I don’t understand the opposition to publicly funded healthcare, how a regarded education is ‘purchased’ and the 17th century resistance to gun control regulation. …I guess you need to be born into it. I think the political minorities have almost as much backing in Australia but are not as extreme and have less volume, so the international effects are minimised.

Relevant to stem cell research, the Colorado Springs Planned Parenthood shooting in November 2015, made me wonder how extreme the fight to protect the rights of a fertilised egg still is. My only explanation for these people is a 16th century belief in a ‘homunculus’ (fully formed miniature human present in every sperm)…Someone please get them a microscope.


Above. The : A 16th century theory for human development. Obviously not real though but an image that seems to exist in the mind of the anti-choice movement

All of this seems contradictory to a country with arguably the most advanced thinking and technologies but I was pleased to see the numbers don’t support it with;

– 2008 Bush allocation of $88 million in NIH funds to human embryonic stem cell research (compared to $381 million to adult stem cell research)

– 2014 Obama allocation of $166 million, while non-embryonic only slightly increased ($443 million), with a large allocation to iPSC projects.

This even indicates the recognised importance of pluripotent technologies over adult somatic technologies.

I wonder though if this balance is also recognised in the public and adult somatic cell spaces. In an effort to sell an alternative to hESC, the potential of adult somatic stem cells was drastically inflated. Recently I have attended a number of adult somatic stem cell talks who describe the expression of Oct4/nanog etc. in their population of choice, even call them pluripotent….though I am yet to see the teratoma/PluriTest, or clinical trial for functional long term grafting behaviour. Literally hundreds of clinical trials on MSCs have been done over the last 15 years so I guess if the data were there, we would have seen it.

MSC clinical trials

Number of registered clinical trials of mesenchymal stem cells-based therapy on

My fears were allayed when reading Don Reed’s book, in which he interviews fantastic adult stem cell researcher and patient advocate, Dr Jan Nolta. When asked if injection of mesenchymal stem cells was a possible cure for Huntington’s Disease, she answered straight out “No,…..But it buys us time”. Herself and Dr Vickie Wheelock agreed that hESC or hiPSC would be needed for the actual cure. It’s refreshing to see this honesty, a recognition that we need to work together, promote both sides, but realise the timelines of expected contribution from each. Saying it is not a cure does not mean it is not important.

So far I have enjoyed a range of meetings, including both Stem Cells on the Mesa and the World Stem Cell Summit on US soil and look forward to ISSCR in June. Unfortunately from Australia it is wildly expensive and time-consuming to travel to all of these meetings….you can fly LAX to Sydney in 15 hours as opposed to the 12 hours it took my husband to get from San Diego to Florida….

Australia US map

Good or bad I think the US is a place where anyone with a decent backing can make changes with great relevance on the International scale. If you can legalise hESC research under a Republican government, you can do anything!

Are you going to the World Stem Cell Summit? Top reasons you should

WSCSBy Heather Main

This year I will be attending the World Stem Cell Summit for the first time (see @WSCSummit on Twitter).

I was surprised when I looked at the program and recognized so few of the names of speakers; which made me question what this event was about, if not focused on stem cell research. This was a relatively naïve step from someone who has spent their entire academic career working on mouse embryonic stem cells and attending academic-focused conferences, far away from human patients and all of the issues and expertise that would be required to take my academic work and apply it to ‘society’ and humans in the clinic….

There are several concurrent tracks at the WSCS;

  • Discovery – latest scientific discoveries in stem cells and regenerative medicine research, with consideration given to clinical product thinking at early discovery stages…bench to industry to bedside is the slogan.
  • Regmed capital conference – advancing investment and commercialization to accelerate cures. Connects regenerative medicine companies to investors, bringing start-up angel capital and new money into the field.
  • Technology innovation showcase – technologies, products and services focus on defining quality systems to meet manufacturing, regulatory, clinical trial needs, specialized expertise, training and sharing data
  • Translation and clinical trials – showcases significant clinical trials from around the world discussing overcoming regulatory obstacles and the role of patients
  • Regenerative services and applications – the emerging role of regenerative medicine in clinical practice aimed at preparing clinicians and hospital administrators transitioning regenerative medicine into day-to-day medical practice and giving families the tools to make informed decisions about future treatments
  • Hot topics and future trends – focusing on bold and innovative solutions, showcasing guru-visionaries and inspiring advocacy leaders as well as the critical unmet need for cell standardization, integrity of scientific progress and how insurance products will revolutionize the cell therapy and storage industries.
  • Ethics, law and societyuniversal consents for research and clinical trials, technology transfer, intellectual property, comparative law; regulatory law; compliance with FTC, FDA, EMA, best practices for IRB’s and ESCRO committees, moratorium on modifying the human germline, right-to-try legislation and more

What struck me in this program is that there is little focus on ‘basic’ research and instead a heavy focus on translational and applied research, representing the vast diversity of stakeholders critical to this. I have been to ISSCR a few times and never seen a session directed to hospital administrators or talks on insurance products. There are so many worlds in this program that as an academic I have never been exposed to and guaranteed I will never master them all. However, I feel that to validate my ‘significance’ slide, I need to learn a little about these fields or at least make contact with experts in these fields.

While we in the pluripotent world are just getting excited about preliminary results from PSC macular degeneration clinical trials, this program shows just how many ‘real world’ technologies and applications there already are, a wealth of knowledge to the researcher who wants to better plan the direction of their technologies to clinical and commercial applications. As someone said to me recently, there are only so many things you can do with cells, you grow them, dissociate them, concentrate them, and deliver them. Whether you do this with adult stem cells or pluripotent stem cells a lot of the practical and regulatory issues are going to overlap so there is a lot to learn from current applications.

What I love about the Genetics Policy Institute and the WSCS is how nicely their goals and focus complement ISSCR. ISSCR guarantees that basic and applied stem cell research will always get the attention and support it deserves. The board of ISSCR is full of PhD and MD titles that ensure this organization will always uphold the values and importance of the scientific method and development of innovative and efficacious treatments. This is not a small job and requires a wealth of scientific knowledge and experience. The GPI represents the ‘real world’ where human interaction determines the success of a technology, regardless of how brilliant it is. To form the right networks for engaging scientists, business, public, patient, policy, finance, insurance, law etc., towards “a positive policy, regulatory and societal framework to allow research to flourish under high ethical and medical standards” is the premiere goal of GPI.

To finish, I hope that every stem cell researcher puts the World Stem Cell Summit high in your priorities to attend and to send your lab members. The vast majority of PhDs/post docs will need to leave academia at some stage and the earlier we are exposed to the plethora of career options required to get our beloved stem cells to the public the better!

Mini-bios on some top finalists for Stem Cell Person of the Year

Heather_MainBy Heather Main

I was a little ashamed of myself that I didn’t know who half of the finalists were in Paul Knoepfler’s Stem Cell Person of the Year Award. I decided to look into it and find out what (or who) I have missed…..Interestingly, 3 of the 7 listed here are not scientists but instead are patients and/or patient advocates, showing the major impact these groups have on progression of our field. I have listed my write-ups of the finalists here alphabetically.

Bill Moss – FSHD sufferer, FSHD global foundation founder and chairman

Bill was diagnosed with FSHD (the most common form of muscular dystrophy) at 28 years old. The youngest child of a gardener, Bill became a masterful businessman and spent 23 years as a senior executive and Executive Director of a pre-eminent Australian investment bank before leaving at 52 years of age to pursue philanthropic initiatives. He has self-funded programs for industry development in Australian aboriginal communities, advocated for disability rights and established the FSHD Global Research Foundation. This foundation funded derivation of the first FSHD affected hESC and successful highthroughput modeling of the disease through development of an efficient protocol to differentiated them to skeletal muscle. 

Jeanne Loring – Academic researcher

Personally I think PluriTest (the bioinformatic test for assessing pluripotent status) alone earns Jeanne a spot in this ‘hall of fame’. Her lab also leads fields including the ‘Frozen Zoo’ (iPSCs from the endangered species), translational projects in arthritis, Alzheimer disease, Parkinson’s disease, autism, and addiction as well as creating collections of iPSC lines for disease modeling and ethnically diverse toxicity testing. Jeanne is also recognized for her public work in ethics, legal issues, clinical use, cell generation and clinical use, the legal implications of patents and stem cell tourism. In December she will be awarded the 2015 World Stem Cell Summit ‘Stem Cell Action Award for advocacy’.

Judy Roberson – Huntington’s Disease patient advocate

Judy is a registered nurse, who now works as a full time volunteer patient advocate for Huntington’s disease. This includes supporting the UC Davis Huntington’s Disease Clinic, the UC Davis Institute for Regenerative Cures, and CIRM (California’s Stem Cell Agency), including legislative advocacy. She was appointed as the first voting patient representative to the FDA Huntington’s Disease Advisory Committee and is past president of the northern California chapter of the Huntington’s Disease Society of America. Judy advocates for the role patient advocates play in driving stem cell sciences towards making the goals a reality.

Michele de Luca and Graziella Pellegrini – academic researchers/clinicians

Professor De Luca, and his principal collaborator Graziella Pellegrini, have worked together over 20 years, towards the use of human epidermal stem cell cultures for life saving burns treatments as well as treatment of repigmentation and piebaldism. The team has also established human limbal stem cell culture for sight restoring corneal regeneration. Michele De Luca is coordinating the first (successful) gene therapy clinical trial for junctional epidermolysis bullosa and studies the stem cell behaviours of epithelial stem cells. Professor Graziella Pellegrini is based at the Centre for Regenerative Medicine “Stefano Ferrari” at the University of Modena and Reggio Emilia and one of the principal scientists on the corneal repair system Holoclar ®.  Together they have achieved Europe’s first approved advanced therapy medicinal product (ATMP) to be integrated into health services for patients across Europe in the future. 

Robert Lanza – ‘child science star’, CSO of Ocata Therapeutics

Reading about Robert Lanza is like reading about a rock star. In TIME magazine’s 2014 100 most influential, in FORTUNE magazine and even suggested to be played by Ben Affleck if his work leads to restoring eyesight to millions. Son of a professional gambler and growing up in Boston, Massachusetts, the weirdest find is that at the age of 14 (1969), he partially induced melanin synthesis in chicken to change the colour of its feathers for a science fair project. While it is hard to find the details of this first study, at the age of 19, with the assistance of Stephen Kuffler and Joshua Sanes at Harvard Medical School, Robert published a complete change in pigmentation in Nature using nucleoprotein from the Harco chicken and a standard cross between the Barred Plymouth Rock hen and the Rhode Island Red rooster. Since this early fascination of genetics, Robert developed methods for deriving hESC lines from single blastomeres in an attempt to avert the ethical discussions of the destruction of human embryos and is now running clinical trials for macular degeneration with hESC derived retinal cells.  Robert is currently Chief Scientific Officer at Ocata Therapeutics (formerly Advanced Cell Technology).

Shoukhrat Mitalipov – academic researcher

Shoukhrat was the first to derive hESC through somatic cell nuclear transfer, publishing in Nature 2013. He is also the ‘father’ of 3-parent IVF where by ‘spindle transfer’ the genetic material of a donor oocyte is swapped out for the DNA of a mother who carries a mitochondrial disorder. This creates a new egg with ‘normal mitochondria’ and nuclear genetic information from the mother, which is then fertilised with the sperm of the father. The technique is successful in rhesus macaques but has not yet been tested in humans. Shoukhrat’s company Mitogenome Therapeutics appears to be pursuing 3-parent IVF in China, because it is not currently allowed by the FDA in the US.

Ted Harada – ALS sufferer and unproven stem cell treatment recipient

Another patient advocate, Ted has received two doses of fetal neural cells in his spinal cord from Emory University in Atlanta as an experimental treatment to slow progression of his ALS. While Ted showed improvement in limb movement, strength and dexterity from the first transplantation his abilities have slowly been regressing, leading to this second treatment. Ted is a strong advocate for “Right To Try” that patients’ choice to receive experimental treatments should be respected and will speed up innovation.  He challenges the idea that patients who are out of options may need to settle for ‘silver standards’ with novel FDA approved treatments taking 10 – 15 years and sometimes nearly a billion dollars. He feels that these patients do not have that time to wait. Refreshingly, he is not a fan of stem cell tourism and the Right-To-Try movement stipulates the treatment has to have completed an FDA phase I portion of a trial and been approved for phase II.

Stem Cells on the Mesa: Highlights from Heather Main

By Heather Main

Mesa, one of my first Spanish words since moving to California. The isolated flat-topped hill with steep sides where I have just had the pleasure of listening to some of the best basic and applied science. Mountains of various sorts formed the metaphor of CIRM 2.0 with Randy Mills (President/CEO of CIRM) describing the ‘giant boulder of love and happiness’ that academia pushes and industry pulls over the mountain of regulation, safety and efficacy bringing cures to patients. The streamlining of regulation makes the mountain smaller to decrease both the push and pull needed.

The meeting was a nice mix of academic and applied research, highly evident was the drive that CIRM funding has ignited in California. Of interest, after 5 years of 91% academic CIRM funding, the next 5 years is focusing towards critical funding towards industry translational projects…CIRM 2.0

Listening to Elaine Fuchs makes you question your worth in the field and when this woman will get a Nobel Prize for her contributions to stem cell sciences. The number of ‘Cell’ and ‘Nature’ references with her name on it in her talk demonstrate her unique ability to conquer the highest levels of science consistently throughout her career. A career spanning therapeutic skin stem cell application to stem cell niche determination, quiescent stem cell identification and now cancer stem cell quiescence, the lessons outlined by Elaine’s Keynote address form a foundation basis for stem cell sciences in both cellular therapy and cancer applications.

Other highlights for me included:Stephanie Cherqui, Ph.D

Stephanie Cherqui (at right), discussed the nanotubular highways for intercellular organelle transport with HSC cellular therapies that lead to macrophage differentiation and delivery of healthy lysosomes for Cystinosis disease rescue phenotypes.

Samuel Pfaff talked about his lab’s identification of miR218 as the most specific motor neuron marker known to date and the mechanistic possibility of its loss of activity, leading to an increase in gene expression deleterious to motor neuron survival, a possible mechanism for ALS.

Shyni Varghese (at left)Shyni Varhese, gave a great talk on production of bone from endogenously recruited cells using hydrogels engineered to bind minerals. The minerals were sufficient to produce bone in acellular scaffolds, while absence of mineral loading lead to fat formation. There was even novelty in Isaac Newton shaped bone deposit.

Pilar Ruiz-Lozano discussed amazing results using FSTL1 loaded collagen matrix to rescue heart regeneration following infarction, from mouse to pigs. The specific activity of FSTL1 from epicardium was essential to this regenerative function, in contrast to non-regenerative glycosylated FSTL1 produced in response to injury by the myocardium.

Joseph Metzger discussed stabilization of Duchenne Muscular Dystrophy dystrophic muscle membranes. These Poloxamer 188 ‘band-aids’ strengthen weaknesses in dystrophic membranes to avoid catastrophic Calcium entry that leads to cellular death. While super interesting, this is really a band-aid treatment, as Joseph says, just like Type 1 Diabetes, there is still room for gene and cellular therapy based cures.

The most confusing part of the meeting for me was the Thursday night ‘public forum’. I’m not sure what this means in California but the public forums I have attended have a majority of audience members from the public and attempt to pass knowledge and excitement about stem cells to a lay audience. While there was some fantastic science, I don’t think I would have understood a word in regard to ‘The promise of regenerative medicine: are we there yet?’ if I was a member of the public.

As my first time at Stem Cells on the MESA I was really impressed by the attitude I sensed, that solid science combined with effective clinical and commercial translation strategies are essential to successes in our field. That basic research is not enough. Second, it was nice to see an equal and unbiased appreciation for material sciences applications, gene therapy treatments, cellular therapy applications and endogenous repair applications. Whatever gets to the post first should ‘win’ for the sake of the patient.