Stem cells: Taking stock in Stockholm

 

STOCKHOLM, Sweden—The Skokie, Ill.-based International Society for Stem Cell Research (ISSCR) will be headed across the Atlantic for its 13^th annual meeting, which will take place June 24-27, 2015, at the Stockholmsmässan Exhibition and Convention Center in Stockholm. Some 4,000 stem cell scientists, bioethicists, clinicians and industry professionals from over 50 countries are expected to show up to present, discuss and learn about the latest discoveries and technologies within the field.

 

“The ISSCR is excited to bring its annual meeting to Stockholm, a city that shares our passion and reputation for great scientific research and collaboration,” says ISSCR President Dr. Rudolf Jaenisch of the Whitehead Institute for Biomedical Research. “We look forward to learning more about the strong work being done in Sweden and across Europe.”

 

Jaenisch notes that Chicago-area ISSCR was founded with “great vision” and that the annual meeting not simply being in the United States is key to its worldwide activities. In just the 13 years leading up to this Swedish venue, he points out that the annual meeting has been held twice in Canada—Vancouver last year and also Toronto—and in Japan, Australia and Spain.

 

Importantly, this year’s meeting is co-sponsored by Sweden’s Wallenberg Institute of Regenerative Medicine (WIRM). WIRM is very active in planning, networking and outreach programs that will contribute to the meeting’s success, Jaenisch notes. In addition, WIRM will host a symposium at the medical university Karolinska Institutet during the annual meeting. This year’s public symposium, “Stem Cells and the Ageing Brain,” will take place June 23, from 5 p.m. to 8 p.m. in the Aula Medica lecture hall at Karolinska Institutet. The symposium is open to the public and free of charge.

 

WIRM is a research institute financed by a research grant from Knut och Alice Wallenbergs Stiftelse. The aim of WIRM is to advance research on the blood system at Karolinska Institutet, both during normal hematopoietic development and in disease. This is accomplished by recruitment of leading international expertise, both at the senior level and at the level of new junior group leaders. WIRM also builds new important research infrastructure for stem cell research and regenerative medicine, including a state-of-the-art fluorescent-activated cell sorting facility supporting core facilities for cellular reprogramming/induced pluripotent stem cells, GMP production of clinical-grade cells, transgenic mouse technology, zebrafish and live-cell imaging.

 

“This is the first year of our affiliation with the Wallenberg Institute, and we expect it to be a long-term relationship,” Jaenisch states.

 

The meeting will open with the Presidential Symposium on June 24 from 1:15 p.m. to 3:15 p.m. The symposium sets the stage for the meeting with world-renowned speakers that include Nobel Prize-winner Shinya Yamanaka. It is also the platform for the formal recognition of the 2015 recipients of the McEwen Award for Innovation and the ISSCR Public Service Award. Another prestigious award, the ISSCR-BD Biosciences Outstanding Young Investigator Award, will be presented during Plenary VI on June 27 from 9 a.m. to 11:20 a.m. and followed by an award lecture.

 

“I look forward to the Presidential Symposium setting the tone for the entire program,” Jaenisch said. “A thread throughout will be the use of stem cells to drive our understanding of development and disease as we explore disease modeling, gene and tissue engineering technologies and other important advances that are bringing stem cells into the clinic.”

 

In fact, key clinical trials are now in the planning stage or have already begun, Jaenisch tells DDNews. “Macular degeneration trials are planned and underway,” he notes. In other developments, gene editing is allowing researchers to correct or add genes at will in both research applications and the clinic. In cancer, immune systems are being reprogrammed to kill cancer cells—for example, in melanoma and prostate disease. “Clinical applications are also being highlighted in workshops this year,” Jaenisch adds.

 

As for notable awards, “The ISSCR is thrilled to present the prestigious McEwen Award for Innovation to Irving Weissman and Hans Clevers, who have each made enormous contributions to stem cell science,” notes Dr. Hans Schöler of the Max Planck Institute for Molecular Biomedicine, chair of the ISSCR’s McEwen Awards selection committee. “Working in the blood and gut systems, respectively, and extending their findings in different tissues, they have defined the concepts and technologies that underpin many avenues of research. Each has made pioneering conceptual advances in disease modeling and regenerative medicine.”

 

“We are privileged to present our ISSCR-BD Biosciences Outstanding Young Investigator Award to Paul Tesar,” Jaenisch adds. “He has leveraged his understanding of mammalian development to create transformative stem cell-based technologies and to enable access to new areas of biology. His accomplishments advance our understanding of human health and would be impressive at any stage, but they are remarkable for someone so early in his career.”

 

The 2015 Annual Meeting Program Committee is chaired by Dr. Leonard Zon of Harvard Medical School and Boston Children’s Hospital, who says he and the rest of the committee worked together over the past year to assemble a diverse program and an international contingent of stem cell researchers, clinicians and industry professionals to share the newest research, technologies and clinical advancements.

 

“When the idea for the International Society for Stem Cell Research was born, nearly 13 years ago, I hoped the stem cell field would have an exponential impact on clinical medicine,” Zon said. “This process has begun, and the field has a bright future, as evidenced by this year’s ISSCR meeting program.”

 

“The basic biology of stem cells has led to brilliant discoveries and served as a foundation for burgeoning therapies,” he continues. “Attendees of ISSCR 2015 will see an increasing clinical focus as the meeting moves toward Friday and Saturday and we learn of cutting-edge approaches now entering the clinic.”

 

Clevers, winner of the McEwen Award for Innovation, will present during the “Disease Modeling” plenary, sharing research published in two recent papers in the scientific journal Cell. The papers describe the development of a culturing system for human liver stem cells, as well as stem cells from pancreatic cancer, discoveries with the potential to revolutionize liver transplantation and aid in the fight against pancreatic cancer, respectively.

 

The “Therapy with Stem Cells” plenary session includes a talk by Dr. Douglas Melton of Harvard University, who led recent work to produce human insulin-producing beta cells in the massive quantities needed for cell transplantation and pharmaceutical purposes. This work represents a leap forward in the quest to find a truly effective treatment for type 1 diabetes. Dr. Allan Robbins of Viacyte will discuss the development of his company’s stem cell-derived encapsulated cell replacement therapy and the initiation of trials to evaluate safety and efficacy.

 

Saturday opens with the “Stem Cells and Immunology” plenary. In this session, Dr. Carl June of the University of Pennsylvania School of Medicine will present his group’s groundbreaking research in developing ways to enhance the body’s own immune system to recognize and kill cancer cells.

 

The final plenary of the meeting, “Making Tissues and Organs,” will feature a talk by Dr. Masayo Takahashi of the RIKEN Center for Developmental Biology. Takahashi is leading the first-ever clinical trial using induced pluripotent stem cells (iPSCs). In 2014, she and her team at RIKEN transplanted a retinal pigment epithelium (RPE) cell sheet derived from iPSCs into a patient suffering from age-related macular degeneration to assess the safety of the transplantation of iPSC-derived RPE sheets.

 

Dr. Robert Langer of the Massachusetts Institute of Technology, a leader in the field of biotechnology and one of the most cited engineers in recent history, will deliver the closing keynote address. Langer holds nearly 1,080 patents worldwide which have been sublicensed to over 250 pharmaceutical, chemical, biotechnology and medical device companies.

 

As far as overall presentations, the ISSCR received more than 2,000 abstracts for the 2015 meeting, resulting in the addition of 20 new speaking slots. A total of 100 speakers will be identified from outstanding abstracts and will present their research in the concurrent tracks. Three poster receptions allow further opportunities for researchers to present and discuss their work.

 

“The posters are always the genesis for some of the meeting’s greatest scientific conversations and collaborations,” Zon says. “Year after year, we hear that networking with peers is one of the most valuable components of the meeting.”

 

Honorees at the 13^th annual meeting of the ISSCR include winners of the McEwen Award for Innovation, the ISSCR-BD Biosciences Outstanding Young Investigator Award and the ISSCR Public Service Award.

 

The McEwen Award will go to Dr. Irving Weissman of the Stanford School of Medicine and Dr. Hans Clevers of the Hubrecht Institute. Supported by the McEwen Centre for Regenerative Medicine, the $100,000 award recognizes original thinking and groundbreaking research pertaining to stem cells or regenerative medicine that opens new avenues of exploration toward the understanding or treatment of human disease or affliction. Past winners include Azim Surani, James Thomson, Rudolf Jaenisch and Kazutoshi Takahashi with Shinya Yamanaka.

 

In 2015, the ISSCR recognizes longstanding contributors to the field Weissman and Clevers for their identification, prospective purification and characterization of somatic (adult) tissue-associated stem cells and advancement of their research findings toward clinical applications.

 

Weissman’s many discoveries have helped map the direction of the stem cell field and have served as the basis for important research and work by scientists all over the world. He was the first to isolate and characterize hematopoietic (blood) stem cells from mice and humans. He developed the approaches and technologies, now widely used within the field, for isolating blood stem and progenitor cells and defining their properties. Weissman also pioneered the extension of his approaches to isolation of other stem cell types, including human nervous system cells and skeletal muscle myogenic stem/progenitor cells. Further, he discovered several independent leukemia stem cells and, more recently, bladder cancer stem cells, head and neck cancer stem cells and malignant melanoma stem cells. Weissman has pursued these discoveries to develop several promising means of cancer therapy.

 

Clevers has been a leader in biomedical sciences and the area of Wnt signaling in colon cancer for more than three decades. He and his lab developed tools to identify and track an adult stem cell population able to give rise to the entire lining of the gut and later to demonstrate that these cells can be isolated and grown in culture as “miniguts,” recapitulating the normal structure and function of the gut. These discoveries are a move toward promising therapies for colon conditions like ulcers, in which the lining of the intestine has been destroyed in patches, and provide a powerful resource for modeling disease pathology and for drug screening.

 

Dr. Paul Tesar of the Case Western Reserve University School of Medicine is the 2015 recipient of this young investigator award, which recognizes exceptional achievements by an ISSCR member and investigator in the early part of their independent career in stem cell research. The winner receives a $7,500 personal award and is invited to present at the ISSCR’s annual meeting. Past winners include Valentina Greco, Marius Wernig, Cédric Blanpain, Robert Blelloch, Joanna Wysocka and Konrad Hochedlinger.

 

Tesar established his independent laboratory five years ago and has rapidly risen to his current position as the Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics and tenured associate professor in the department of genetics and genome sciences at Case Western. Tesar’s studies have shaped the global understanding of both pluripotent stem cell and oligodendrocyte biology. His seminal and highly cited report on epiblast stem cells, published in Nature in 2007, along with similar findings by Pedersen, Vallier and colleagues, led to a complete shift in the understanding of how pluripotency is regulated in the mammalian embryo. He has continued to provide high-impact contributions to the field, pioneering new methods to generate and mature oligodendrocyte progenitor cells and using these to enhance repair in animal models of multiple sclerosis.

 

Dr. Alan Trounson of the MIMR-PHI Institute of Medical Research is this year’s honoree for outstanding contributions of public service to the fields of stem cell research and regenerative medicine. Winners for this award are selected by the ISSCR board of directors. Past winners include joint recipients Paolo Bianco, Elena Cattaneo and Michele De Luca, Hiromitsu Ogawa and Betty Jean Crouch Ogawa, Rob and Cheryl McEwen and Robert Klein.

 

Trounson was selected for his service as a visible and effective spokesperson for the field on an international level. Trounson is renowned for his pioneering work in in-vitro fertilization and other reproductive technologies, and was an early researcher and advocate for the use of human embryonic stem cells in medical research. As founder of the Australian Stem Cell Centre and president of the California Institute of Regenerative Medicine, he propelled the development of programs with strong public outreach components, encouraging dialogue between researchers and their communities. Trounson was a founding board member of the ISSCR and integral in bringing the ISSCR’s annual meeting to Cairns, Australia in 2007, the society’s first meeting outside of North America.

 

 

Rounding up some recent news about stem cell research as ISSCR 2015 approaches

 

By Jeffrey Bouley

 

With the Chicago-area-based International Society for Stem Cell Research (ISSCR) making yet another global foray outside the United States and Canada with its latest annual meeting, we thought we’d do a grand tour of our own and let you know about a few recent pieces of stem cell news.

 

 

SEOUL—According to research results coming out of a Phase 1 clinical trial in South Korea, stem cells could be a safe therapy for patients with amyotrophic lateral sclerosis (ALS). Details of the trial were published in the May issue of STEM CELLS Translational Medicine.

 

The trial was the next phase of research into stem cells and ALS being conducted at Hanyang University (HU) and Corestem Inc., both in Seoul, and Inje University College of Medicine in Busan. The HU team’s Phase 1 trial had two goals: to test whether stem cells were a safe treatment for ALS and to learn whether two injections of the cells might prove more beneficial than a single injection.

 

“In our pilot study, we followed a group of ALS patients for six months after giving them a single injection of mesenchymal stromal cells (MSCs) and found the treatment to be both safe and feasible,” said the trial’s co-leader Dr. Seung Hyun Kim, director of Hanyang University Hospital’s Cell Therapy Center and professor in HU’s department of neurology. “In this next phase, we wanted to see if two injections would prove even more beneficial, and we wanted to follow the participants for a longer period of time to determine if the treatment proved safe for a longer term than in the pilot phase.”

 

MSCs, which are found in bone marrow, generate bone, cartilage and fat cells that support the formation of blood and fibrous connective tissue. They have emerged as a potentially promising treatment for ALS due to their ability to regenerate lost or damaged cells and for their anti-inflammatory capabilities.

 

Eight patients with definite or probable ALS were enrolled in the new study, although one died shortly after enrollment. After a three-month lead-in period, MSCs were isolated from each patient’s bone marrow two times, at an interval of 26 days, with each group of MSCs then expanded in the lab for 28 days before being injected into the donor patients. The seven patients received intrathecal (cerebrospinal fluid space) injections of their own MSCs in two separate treatments given 26 days apart.

 

Kim said, “Intrathecal injections have the advantages of not only avoiding invasive surgical technique that had been done in the previous other group’s study, but also it’s easy to do repeated procedures without harm to the patients.”

 

Their ALS functional status and safety was then evaluated for 12 months after the first injection.

 

 “No serious adverse events were observed during this period,” reported co-leader Dr. Ki-Wook Oh, also of HU’s neurology department. “Additionally, there was no advancement in ALS symptoms in any of the patients during the 12-month period.”

 

“This study shows that stem cells as a therapeutic approach for ALS are feasible and well tolerated at least for 12 months, supporting the need for a late-stage clinical trial to examine their in-depth safety, biological effects and efficacy,” said Kim. “Randomized, semi-double blind controlled Phase 2 clinical data on 72 ALS patients, which recently was submitted to the Korean FDA, will be released in the near future.”

 

 

NEWARK, Calif.—StemCells Inc. announced near the end of April that it had closed its previously announced offering of common stock and warrants. The company received total proceeds, net of offering expenses, underwriting discounts and commissions of approximately $23.35 million. The warrants have an exercise price of $0.85 per share, are exercisable immediately and will expire five years from the date of issuance. If the warrants are exercised in full, StemCells, Inc. will receive additional proceeds of approximately $26.2 million. The underwriters have a 30-day option to purchase up to an additional 5,357,250 shares of common stock to cover over-allotments. The company is currently engaged in clinical development of its platform technology, HuCNS-SC cells (purified human neural stem cells) as a potential treatment for disorders of the central nervous system.

 

 

NEW YORK—April 23 saw Tisch MS Research Center of New York (Tisch MSRCNY) announce encouraging preliminary results from its Phase 1 trial using autologous neural stem cells in the treatment of multiple sclerosis. The results were selected for presentation during the Multiple Sclerosis Highlights in the Field session at the 67^th American Academy of Neurology Annual Meeting in Washington, D.C.

 

Tisch MSRCNY research showed that in the interim analysis, six of nine patients are exhibiting increased motor strength, improved bladder function and an enhanced quality of life. Importantly, the treatments are well tolerated and thus far no serious adverse events were reported.

 

“This preliminary data is encouraging because in addition to helping establish safety and tolerability, the trial is yielding some positive therapeutic results even at this early stage,” said Dr. Saud A. Sadiq, chief research scientist at Tisch MSRCNY and the study’s principal investigator. He cautioned, however, that these results are an interim analysis and definitive conclusions will only be made upon completion of the trial.

 

The study investigates a pioneering regenerative strategy using stem cells harvested from the patient’s own bone marrow. These stem cells are injected intrathecally (into the cerebrospinal fluid surrounding the spinal cord) in 20 participants who meet the inclusion criteria for the trial. This is an open-label safety and tolerability study, and all activities are conducted at Tisch MSRCNY and affiliated International Multiple Sclerosis Management Practice. The interim analysis reports on the first nine patients that have received at least one treatment of stem cells.

 

 

CLEVELAND—Athersys is a biotech developing the MultiStem cell therapy product, a patented, adult-derived “off-the-shelf” stem cell product initially for disease indications in the cardiovascular, neurological, inflammatory and immune disease areas. Mid-April saw it focus on the neurological side with the announcement of interim results from its exploratory Phase 2 clinical study of the intravenous administration of MultiStem to treat patients who have suffered an ischemic stroke. The study results are said to have demonstrated “favorable safety and tolerability for MultiStem, consistent with prior studies” but, with respect to the primary and secondary endpoints, the cell therapy did not show a difference at 90 days compared to placebo.

 

However, MultiStem treatment was associated with lower rates of mortality and life-threatening adverse events, infections and pulmonary events. Furthermore, post-hoc analysis shows that patients who received MultiStem treatment earlier in the treatment window had more robust recovery rates in comparison to placebo and relative to patients who received later MultiStem treatment.

 

“This exploratory Phase 2 trial represents our first clinical study in stroke and was designed to evaluate the safety and efficacy of a single dose of MultiStem 24 to 48 hours following the occurrence of the stroke. This treatment window extends well beyond the limits of current standard of care, treatment with tPA, which may only be administered within the first several hours after a stroke,” commented Dr. Gil Van Bokkelen, chairman and CEO of Athersys. “Going into this trial, based on extensive preclinical work we have conducted internally and with independent labs, we anticipated that administration of MultiStem could provide several mechanisms of benefit, including down-regulation of key inflammatory pathways, up-regulation of multiple reparative mechanisms and could also extend the treatment window in a meaningful way.”

 

“While the trial did not achieve the primary or component secondary endpoints, we believe the evidence indicating that patients who received MultiStem treatment early appeared to exhibit meaningfully better recovery is very important and promising,” he continued. “The results appear to confirm that our window of intervention with MultiStem therapy may extend well beyond the limits of current care. Additional key observations from the trial also appear consistent with key elements of our initial hypothesis … We anticipate additional data and information from the study and will conduct further analyses to generate more insight about the potential for MultiStem treatment in this area.”

 

He also noted that the company continues to advance other clinical programs in acute myocardial infarction and acute respiratory distress syndrome.

 

 

Disease Modeling

Making Tissues and Organs

Immunology and Stem Cells

Pluripotency, Mechanisms of Reprogramming

Regeneration and Engraftment

Therapy with Stem Cells

 

Cell Adhesion, Motility and Migration

Control and Induction of Pluripotency

Disease Modeling

Epigenetics

Epithelial and Mesenchymal Stem Cells

Ethics and Public Policy; History of Science;

Communication; Education

Germline and RNA Biology

Hematopoiesis

Lineage Relationships and Clonality

Modeling Disease with iPSCs

Neural Degeneration

Neural Stem Cells and Differentiation

Pancreas, Lung, Liver and Intestine

Road to the Clinic

Single Cell Biology

Stem Cell Niche

Stem Cell Regulatory Networks and Models

Stem Cells and Cancer

Stem Cells in Model Organisms

Tissue Engineering, Organ Development and

Regeneration

Transdifferentiation and Reprogramming

 

Fred H. Gage, Ph.D., Salk Institute for Biological Sciences, United States

Jürgen Knoblich, Ph.D., Institute of Molecular Biotechnology, Austria

Shinya YamanakPa, M.D., Ph.D., Center for iPS Cell Research & Application, Japan

Jeannie Lee, M.D., Ph.D., Massachusetts General Hospital, United States

 

 

The International Society for Stem Cell Research is an independent, nonprofit membership organization established to promote and foster the exchange and dissemination of information and ideas relating to stem cells, to encourage the general field of research involving stem cells and to promote professional and public education in all areas of stem cell research and application.

 

The 14^th ISSCR Annual Meeting will be held June 22-25, 2016, at the Moscone Center in San Francisco.

 

 

On Wednesday, June 24 at the ISSCR 2015 annual meeting, from 8:30 a.m. to 12:30 p.m., attendees are encouraged to include the Focus Sessions, which are parallel, in-depth educational opportunities in science, society and education at the meeting organized by members. The goal of these sessions is to increase the representation of topics at the meeting that are of interest to constituencies within the ISSCR but are difficult to adequately represent within the main scientific program.

 

Gain first-hand knowledge on how to develop a business case and pitch your idea. What are the expectations of venture capitalists and pharma when considering a new opportunity? What does the new company look like and how does it function? Network with your peers and representatives from industry, academia and biopharma as well as successful entrepreneurs to discuss their personal experiences and view to expand your vision of novel funding models.

 

This session will bring together experts in stem cell biology and human genomics to discuss recent progress and challenges in developing cell-based functional genomic assays at scale for common diseases in cohort studies, as well as highlight induced pluripotent stem cell (iPSC) resources available for genomic research. There will be a session on the generation of large scale iPSC cohorts and another on the functional annotation of human genetic variants.

 

Topics for discussion in this session will include the scientific applications of large collections, establishment of reference lines and standards for quality control, the challenges faced in distributing iPSCs across borders, and the role of funding agencies in support and coordination of large collections. An important thematic emphasis will be on the necessity for standardization and cooperation among the groups in this field from the earliest days. There will be two sessions, one on quality control and characterization and the other on informatics and global coordination.