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ISSCR 2018 show preview: Heading Down Under to bring up matters about stem cells
International Society for Stem Cell Research
ISSCR 2018 Annual Meeting
June 20-23, 2018
Melbourne Convention & Exhibition Centre
Heading Down Under to bring up matters about stem cells
International Society for Stem Cell Research’s 2018 annual meeting to be hosted in Australia
After being hosted by U.S. cities the past couple years, the International Society for Stem Cell Research (ISSCR) reminds us about the “international” in its name by hitting the global road, as it were, and heading to Melbourne, Australia, in June for its 16th annual meeting.
As ISSCR President Dr. Hans Clevers noted last year when talking about the 2018 venue, “Melbourne has very strong universities and university hospitals, and at the center of all that is the WEHI [the Walter and Eliza Hall Institute of Medical Research, Australia’s oldest medical research institute]. I think it’s going to be a great place to visit and great for the Australians to have us there. Also, it’s a part of the world where a lot of our members come from—Asia and Australia. The ISSCR has a policy to have two annual meetings in the U.S. and the third one somewhere else in the world ... and this is a fantastic place.”
In general, Clevers notes, stem cell science in Australia is strong: “It has a long tradition and many of the growth factor we now know are important for immune cells and for stem cells were discovered at the WEHI or associated with the WEHI. There are several companies that are very successful that try to develop stem cell-based therapies; again, multiple research institutions in and around Melbourne, Sydney, Adelaide, Brisbane that focus on regenerative medicine and stem cell therapies.”
For 2018 Program Committee Chair Dr. Melissa Little, this year’s location has a more personal spin, as she is the director of the Kidney Research Laboratory at Murdoch Children’s Research Institute in Australia.
“I’m really excited about the prospect of having ISSCR 2018 in Melbourne. It’s going to be a wonderful meeting,” Little said in a video talking about this year’s scientific program. “All the plenary speakers are in place. We have Doug Melton speaking [for the Ernest McCulloch Lecture]. We have Patrick Tam [as the Anne McLaren Memorial Lecture speaker], who will be well known to many of the Australians—he’s a developmental biologist. We have Jennifer Doudna coming to talk about CRISPR/Cas editing [in the keynote address]. It’s a really fantastic plenary program.”
In trying to cover the breadth of stem cell science, Little notes that they have taken care to make sure sufficient coverage has been given to neural stem cells, epithelial stem cells, pluripotency itself and generating complex tissues, as well as translating that into drug screening and treatments.
“As with most ISSCR meetings, we’re trying to cover the spectrum of stem cell biology right through from the fundamental developmental biology through to the technical advances that are being made, the application to disease modeling and right into the clinic,” she said.
Although the ISSCR did not indicate that anything new was added this year, the organization did tell DDNews that for the second year, the meeting will have the Job Match onsite at the meeting, based on the success of this addition last year. At Job Match, potential candidates can contact employers who post job openings and plan to meet onsite in Melbourne.
Also returning for its second year is a Clinical Advances in Stem Cell Research program the day before the opening of the meeting, which ISSCR notes is designed for physicians, scientists and others interested in clinical applications of stem cell research.
That said, a lack of “new” features—leaving aside that different speakers and topics each year is already new content on an annual basis—is in many ways a good thing for ISSCR and its annual meeting. Clevers noted that the program will probably look very similar in general terms to that of the Boston meeting last year, as the growth and development of the ISSCR and stem cell science field have both matured and the ISSCR program is starting to take on what, for lack of a better term, is the “ideal” format.
But as far as what might be slightly different from past years in general, and perhaps even last year’s event, Clevers said: “As for the scientific program for this meeting, what we’ve seen over the years are more and more clinical angles to what we are doing. Stem cell science used to be very basic; very fundamental—we basically had to discover everything from scratch. We’re now starting to see the first applications, so some of the emphasis of the program is not only trying to understand stem cells but also seeing how we can try to apply them, use them, for diagnostics but also for therapeutics.”
The ISSCR provided some insight to DDNews as to what might appeal to our readers in particular at the event, telling us that many scientific presentations at the meeting will focus on drug discovery in a variety of areas, including in particular cardiovascular disease, cystic fibrosis, neurological disorders and cancer, and pointing out as well that “The scientific program at the meeting provides a detailed list and description of the science, scheduled for both plenary and concurrent sessions.”
On June 21, for example, there are concurrent sessions on disease modeling, cardiac development and disease, followed the next day by sessions on organoid modeling of disease, nervous system disease and a plenary on stem cell-based disease modeling. Meanwhile, on June 23, ISSCR notes, “there are sessions on stem cells and cancer and the road to the clinic, all feature talks relevant to drug discovery.”
Clever also noted in a welcome letter to the 2018 meeting on the ISSCR website: “Focus Sessions the morning of 20 June are organized by a variety of stakeholders and provide insights on specific topics of scientific interest. In addition, 14 Innovation Showcases on 21 and 22 June will highlight products, tools and technologies that can enhance your research.”
As for those and other highlights at the meeting, ISSCR noted in an email to DDNews: “Innovation showcases are held on the 21st and 22nd in June in the mornings and feature new and updated products, tools and technologies, with demonstrations of how they can be used in the lab. Many of these focus on drug discovery, including iPSC drug screening, 3D bioengineered human heart-in-a-jar, raw materials for cell and gene therapy manufacturing, human pluripotent stem cell quality and several other topics.”
And, as Clever says of the exhibitions, “You won’t want to miss the exhibit hall, which always features the most up-to-date research tools and technologies. The hall is open throughout the meeting, giving you a lot of time to catch up with the latest company representatives and service providers and learn about products for your lab. This is always a good time to connect with colleagues and check out new science at the poster receptions. We expect more than 100 companies in the exhibit hall at ISSCR 2018.”
As for next year, ISSCR reports that planning is already underway for the June 26-29, 2019, meeting in Los Angeles, with the Program Committee developing “a robust scientific program.” The 2019 meeting is expected to emphasize contributions of young investigators, offering added opportunities to showcase science from this group of scientists.
Notable speakers at ISSCR 2018
Plenary sessions and speakers
Recapitulating Development from Stem Cells
Systems Biology of Heterogeneity
New Technologies in Stem Cell Engineering
Stem Cell-Based Disease Modeling
Cancer Stem Cells
Moving to the Clinic: Gene and Stem Cell Therapies
Concurrent sessions and speakers
Cardiac Development and Disease
Epigenetics and Genetic Regulatory Networks
Epithelial Stem Cells
Homeostasis, Metabolism and Aging
Mechanisms of Reprogramming I: To Pluripotency
Mechanisms of Reprogramming II: Transdifferentiation Between Lineages
Muscle Stem Cells
Nervous System Disease
Organoids in Modeling Disease and Development
Road to the Clinic I
Road to the Clinic II
Stem Cell Niches
Stem Cells and Cancer
Stem Cells in Organ Development and Maintenance
ISSCR annual meeting by the numbers
35 scientific sessions
33 hours of scientific programming
20+ hours of networking
STEM CELLS NEWS ROUNDUP
In honor of the ISSCR 2018 show coming up, here are some recent news items related to stem cell science:
Stem cells show long-term success in treating severe peripheral arterial disease
DURHAM, N.C.—A long-term study of patients who received stem cells to treat angiitis-induced critical limb ischemia (AICLI) reportedly shows the cells to be both safe and effective. The study, published in STEM CELLS Translational Medicine (SCTM), could lead to an option for those who suffer from this serious form of peripheral arterial disease.
AICLI is caused by an inflammation of the blood vessels that leads to a severe blockage in the arteries of the lower or upper extremities. It causes severe pain and impaired mobility, and can even lead to amputation and death. While endovascular and surgical reconstruction are the mainstream treatments for critical limb ischemia (CLI), these classical treatments are unfeasible in approximately 15 to 20 percent of patients.
Stem cell therapy is a promising option for these otherwise no-option CLI patients. As one of the promising stem cell therapies, purified CD34+ cell transplantation (PuCeT) has shown favorable short-term results, but prior to this new study no one had looked at its long-term outcome.
In the study published in SCTM, researchers at Zhongshan Hospital (affiliated with Fudan University) in Shanghai tracked 27 AICLI patients for five years after each had received an intramuscular injection of PuCeT to treat their disease. “The primary endpoint—major-amputation-free survival rate—as well as secondary endpoints such as peak pain-free walking time and the scale of the patient’s pain, were routinely evaluated during the five-year follow-up period,” said Dr. Zhihui Dong who, along with his Department of Vascular Surgery colleague Dr. Weiguo Fu, served as corresponding authors on the study.
The results showed that the major-amputation-free survival rate of these patients was 88.89 percent, the pain-free walking time Increased nearly sixfold and the level of pain they experienced was reduced by more than half.
“Notably, in 17 patients (65.38 percent) not only were their limbs saved, but they also fully recovered their labor competence and returned to their original jobs by week 260. PuCeT demonstrated long-term efficacy and durability as a treatment of AICLI, not only in achieving limb salvage but also in recovering the labor competence and improving the patient’s quality of life” Fu added.
“These long-term results, involving 27 patients, suggest a potential new cell therapy for this debilitating disease,” said Anthony Atala, M.D., Editor-in-Chief of SCTM and director of the Wake Forest institute for Regenerative Medicine. “This is especially significant because until now, many of these patients had no treatment option.”
TARA founders grows adult-like human heart tissue in just four weeks
NEW YORK—TARA Biosystems Inc., a company offering physiologically relevant “heart-on-a-chip” tissue models for drug discovery and development applications, recently announced the publication of a landmark cardiac tissue maturation study, in the scientific journal Nature, led by two of TARA’s scientific co-founders, Dr. Gordana Vunjak-Novakovic and Dr. Kacey Ronaldson-Bouchard.
TARA Biosystems offers bioanalytical testing services on its human stem cell-derived cardiac tissue platform. The company’s Biowire II platform enables the maturation of induced pluripotent stem cells (iPSCs) into tissues that achieve an adult-like phenotype. These physiologically relevant in-vitro models facilitate early cardiac risk assessment of drug discovery candidates and accelerate discovery efforts for novel heart medicines via disease modeling and phenotypic screening capabilities.
The paper, authored by Ronaldson-Bouchard et al. and entitled “Advanced maturation of human cardiac tissue grown from pluripotent stem cells,” was published online in Nature on April 4. The authors describe methods and outcomes of a four-week tissue maturation protocol, which represents a significant reduction in the duration of maturation regimens reported to-date. Additionally, the resultant tissues displayed the structural and functional features of mature human heart muscle not previously reported in the literature. Specifically, the tissues displayed adult-like gene expression profiles, extensive registers of sarcomeres, physiologic sarcomere length (2.2 µm) and density of mitochondria (30 percent), the presence of transverse tubules (t-tubules), oxidative metabolism, positive force-frequency relationship and functional calcium handling.
“This study sets the bar for engineered human cardiac tissue and brings us ever closer to being able to truly recapitulate the function and physiology of the human heart in vitro,” said Dr. Michael P. Graziano, chief scientific officer of TARA Biosystems. “The work has important implications for the discovery and development of novel medicines for heart failure, where discovery efforts and advances have been held back due to the lack of relevant models. We congratulate our scientific colleagues on their remarkable achievements.”
Funding for clinical trial using MultiStem to treat trauma patients
CLEVELAND—The University of Texas Health Science Center at Houston (UTHealth) and Athersys Inc. in April announced plans to conduct a Phase 2 clinical trial evaluating Athersys’ MultiStem cell therapy for early treatment and prevention of complications after severe traumatic injury. This first-ever study of a cell therapy for treatment of a wide range of traumatic injuries will be conducted at Memorial Hermann-Texas Medical Center, one of the busiest level-1 trauma centers in the United States.
In conjunction with this planned study, UTHealth reported that its McGovern Medical School has received a grant award from the Medical Technology Enterprise Consortium (MTEC) to support the study. The MTEC grant will provide $2 million in funding and the Memorial Hermann Foundation will provide an additional $1.5 million.
Athersys will provide the investigational clinical product for the conduct of the trial, as well as regulatory and operational support, as its contribution to the trial. Dr. Charles S. Cox Jr., the George and Cynthia Mitchell Distinguished Chair in Neurosciences in the Department of Pediatric Surgery and co-director of the Red Duke Trauma Institute at Memorial Hermann-Texas Medical Center, will serve as principal investigator. Co-investigators are Dr. Charles Wade and Dr. John B. Holcomb. Memorial Hermann-Texas Medical Center is the teaching hospital of McGovern Medical School.
“Traumatic injury is the leading cause of death and disability among children and members of the military, and also has a significant impact on the elderly,” commented Cox. “Extensive clinical experience indicates that following serious trauma, an acute hyperinflammatory response is frequently triggered, resulting in systemic inflammatory response syndrome, a condition that can impair recovery and lead to additional complications. Our prior research demonstrates that administration of MultiStem following acute neurological injury can help improve recovery and reduce the occurrence or severity of certain complications, so we are excited about the clinical potential in this area.”
The objective of the clinical study, as proposed by UTHealth in its grant application, is to evaluate the safety and effectiveness of MultiStem for the treatment of severely injured patients for the prevention and early treatment of complications after severe traumatic injury. The proposed study is anticipated to be a randomized, double-blind, placebo-controlled Phase 2 clinical trial that will enroll approximately 150 severely-injured trauma patients within hours of hospitalization who have survived initial treatment and are admitted to the intensive care unit. These patients will be randomly assigned to receive MultiStem or placebo, and both groups will receive standard care for their injuries.
The MTEC grant will provide funding for approximately 50 percent of the trial cost, with additional funding being provided by the Memorial Hermann Foundation. The proposed Phase 2 clinical trial must still go through review and approval by the U.S. Food and Drug Administration, and therefore, the design is subject to additional input.
“Our preclinical data suggest that administration of MultiStem following injury mitigates the inflammatory cascade that ensues after traumatic injury that causes considerable damage to end organs, such as the lungs and kidneys,” said Dr. Robert Mays, vice president of Athersys and head of the company’s neuroscience programs. “We and the team at UTHealth also believe MultiStem has the potential to respond to signals of inflammation and tissue damage in various ways, including protection of injured cells, stimulation of new blood vessels and the recruitment of other cell types to promote tissue repair and healing, as well as the reduction of complications following the initial injury.
“Now that the formal grant award has been awarded, we will continue our preparations with UTHealth to finalize the design and planning for the study and will subsequently present that information to the FDA and other relevant regulators for their review, consideration and input.”
Vascugen licenses stem cell technology for blood vessel regeneration
INDIANAPOLIS—Vascugen Inc. has licensed a suite of intellectual property developed at the Indiana University (IU) School of Medicine related to blood vessel formation from adult stem cells. The regenerative medicine company is focused on finding therapies to repair tissues damaged by reduced blood flow due to disease or injury.
The worldwide, exclusive licenses include patent rights to core intellectual property developed by Dr. Mervin C. Yoder, a Vascugen founder and IU distinguished professor emeritus. They broadly cover related products and services for research, diagnostics, therapeutics, tissue engineering and 3-D printing applications arising from the technology. The Yoder lab was the first to discover rare cells that are responsible for the formation of new blood vessels in the body and to then develop methods for manufacturing those cells.
“Injuries or degenerative diseases of the vasculature affect hundreds of millions of patients worldwide,” said Yoder, who is chief scientific officer of Vascugen. “Our research seeks to understand how a healthy vasculature is maintained and propagated. I am thrilled to now advance these discoveries into clinical applications with the potential to benefit patients.”
According to the National Heart, Lung, and Blood Institute, one in 20 Americans older than age 50 has peripheral artery disease (PAD). Often called “hardening of the arteries,” the chronic condition develops when extra cholesterol in the bloodstream collects along the walls of arteries. This buildup, or plaque, reduces or blocks blood flow and is the leading cause of limb amputations. More than half of patients who receive an amputation die within five years, a figure that is higher than the mortality rates for breast, colon and prostate cancers.
“Some patients with severe forms of PAD are left with no treatment options,” said Carter Cliff, CEO of Vascugen. “We are taking a new approach to addressing this unmet need. In preclinical studies, our product has been shown capable of restoring blood flow to oxygen-starved tissues. Vascugen is advancing the translation of this discovery into a safe and effective therapy.”
Vascugen licensed the blood vessel formation technologies from the IU Innovation and Commercialization Office.