Show Preview: ISSCR 2016--Stem cells in San Francisco

Following a couple of times outside the United States, ISSCR brings its annual meeting on stem cell research to Northern California’s Bay Area

Register for free to listen to this article
Listen with Speechify
International Society for Stem Cell Research 14th annual meeting
ISSCR 2016
June 22-25, 2016
Moscone Center West
San Francisco, California
Stem cells in San Francisco
Following a couple of times outside the United States, ISSCR brings its annual meeting on stem cell research to Northern California’s Bay Area
SAN FRANCISCO—The International Society for Stem Cell Research (ISSCR) is based in the Greater Chicago area, but it’s done a good job of living up to the “international” in its name over the years, with seven of the past 13 annual meetings taking place outside the United States—three times in Canada and also in Sweden, Japan, Spain and Australia. Now, for the 14th annual meeting, ISSCR 2016 brings the show for a third go-round in San Francisco, the site of its third and eighth meetings.
“There is a great deal of excitement around stem cells in California, and together with our co-sponsor, the California Institute for Regenerative Medicine (CIRM), we look forward to sharing this excitement with attendees. The meeting will connect researchers from around the world with the science most relevant to their work and foster collaboration that will drive new breakthroughs and advances in the field,” says ISSCR President Dr. Sean J. Morrison.
“The world of stem cells has changed significantly since 2010, when the ISSCR last held the annual meeting in San Francisco,” he continues. “Meeting attendees will be treated to a snapshot of the field and will hear about the most innovative research in 2016. The meeting’s plenary sessions will showcase our basic understanding of stem cell biology and how we are using that foundation for understanding disease to create therapies.”
Opening up the meeting on June 22 at San Francisco’s Moscone Center West will be the Presidential Symposium, featuring an emphasis on stem cells and cancer. Speakers at this symposium will include John Dick, who is credited with formulating a breakthrough theory of the role of stem cells in leukemia, and Pier Paolo Pandolfi, who will address the issue of the molecular mechanisms and genetic underpinnings of cancer and targeted therapeutic strategies coming out of that.
Other Presidential Symposium speakers will be Dr. Irving L. Weissman of Stanford University and Dr. Elaine Fuchs of Rockefeller University.
The Presidential Symposium will also include the formal recognition of the winners of ISSCR’s McEwen Award for Innovation and an award lecture presented by Austin Smith, one of the honorees. Attendees will hear from the winner of the ISSCR Dr. Susan Lim Outstanding Young Investigator Award, and there will also be the ISSCR Tobias Award Lecture—new this year—supported by the Tobias Foundation to recognize original and promising basic hematology research field as well as direct translational or clinical research related to cell therapy in hematological disorders. More on the awards and awardees can be found in the article “ISSCR gives out trio of prestigious awards.”
This year, the ISSCR is expanding its scientific program offerings so that attendees have the opportunity to delve into a greater breadth of topics. The meeting will include 28 concurrent sessions with 56 invited and 112 abstract-selected oral presentations. In addition, three poster sessions will provide additional opportunities to present and discuss work with fellow scientists and leaders in the field.
Expanded Focus Session programming on Wednesday morning is organized by different stakeholders to offer an in-depth look at different aspects of stem cell biology and opportunities in the field, ISSCR tells DDNews, and it is open to all registered attendees.
Again this year, ISSCR is offering a Workshop on Clinical Translation the day before the meeting, though separate registration is required for this event.
In addition to an expanded scientific program, the ISSCR has added additional networking opportunities: two Attendee Orientations that help registrants navigate the meeting and a new Career Fair that allows attendees to interact with companies looking to hire in the stem cell field.
ISSCR notes that its leadership is always looking for ways to “enhance the scientific program and maximize opportunities to interact around the latest breakthroughs and advances in science,” and notes that the meeting next year will be held in Boston, co-sponsored by the Harvard Stem Cell Institute, with ISSCR looking forward to drawing from the rich scientific backdrop that Boston offers in terms of academia and industry.
Next year, ISSCR expects to offer a Physicians Education Program, which will likely be an independent event aimed at a clinical audience.
Getting back to this year, though, Morrison tells DDNews, “The meeting features the most innovative research in 2016. The plenary sessions showcase our basic understanding of stem cell biology and how we are using that foundation for understanding disease to create therapies.”
One of the plenary sessions at the meeting, “Cellular Plasticity and Reprogramming,” features Nobel laureate Shinya Yamanaka of the Center for iPS Cell Research, whose work focuses on cell reprogramming. Other plenary sessions throughout the meeting include “Tissue Growth and Morphogenesis,” “Gene Networks and Epigenetics,” “Gene Therapy and Stem Cells” and “Disease Modeling Using Stem Cells.”
The closing plenary on June 25, “Cell Therapy in Clinical Trials,” focuses on the advancement of stem cell discovery into the clinic and represents ISSCR’s international breadth with its three speakers. It features Roger Barker of the University of Cambridge in the United Kingdom, whose work focuses on therapies for neurodegenerative disorders; Koji Eto of Kyoto University in Japan, who studies the generation of blood cells for clinical application; and Edwin Stone of the University of Iowa in the United States, whose focus is the study and treatment of a wide variety of inherited retinal diseases.
There is also a symposium for a public audience called “The Multi-talented Stem Cell: Unlocking the Clinical Potential.” It will highlight how researchers are developing cutting-edge stem cell treatments across a range of disease areas.
All in all, the ISSCR expects to bring together approximately 4,000 stem cell scientists, bioethicists, clinicians and industry professionals from over 50 countries to present and discuss the latest discoveries and technologies within the field.
“The ISSCR annual meeting is the definitive international conference for stem cell research, focusing on discoveries and innovations that are moving the field forward,” Morrison tells DDNews. “Whether you are a scientist at the bench, in industry or in a clinical setting, the meeting provides invaluable opportunities to learn and discuss the science most relevant to your work. Opportunities to meet and collaborate with scientists from around the world can lead to breakthroughs that advance the field for years to come.”
ISSCR 2017 Annual Meeting
June 14-17, 2017
Boston, Massachusetts
Co-sponsored by the Harvard Stem Cell Institute
ISSCR gives out trio of prestigious awards
The announcement about ISSCR’s four winners for three awards came out in February, but the formal recognition takes place at ISSCR 2016. Those awards are the McEwen Award for Innovation, going  jointly to Dr. Austin Smith of the Wellcome Trust Centre for Stem Cell Research and Institute for Stem Cell Biology and Dr. Qi-Long Ying of the University of Southern California; the ISSCR Dr. Susan Lim Outstanding Young Investigator Award, going to Dr. Fernando Camargo of Boston Children’s Hospital; and the ISSCR Tobias Award Lecture, which honors Dr. Leonard Zon of Boston Children’s Hospital.
The McEwen Award for Innovation, supported by the McEwen Centre for Regenerative Medicine, 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. The winner receives $100,000. Past winners include Irving Weissman and Hans Clevers, Azim Surani, James Thomson, Rudolf Jaenisch, and Kazutoshi Takahashi and Shinya Yamanaka.
According to ISSCR, award recipient Smith has shaped our understanding of embryo stem cell biology for more than 25 years, and the discoveries of Smith and co-winner Ying have had important conceptual and practical impact on stem cell biology. Smith’s research has largely focused on embryonic stem (ES) cells and their relationship to the unspecialized cells resident in the mammalian embryo that go on to seed the many tissues and organs of the body.
In 2003, he and Ying showed that mouse ES cells can be sustained in culture by a specific combination of growth factors, leukemia inhibitory factor and bone morphogenetic protein. They proposed that these cytokines act by inhibiting their differentiation to specialized cells and, in a landmark 2008 paper, confirmed this hypothesis by using small molecules to mimic this effect. This research revealed a “ground state” of pluripotency. These findings enabled new ES cell lines to be developed from refractory mouse strains and paved the way for the extension of ES cell-directed genetic engineering into the rat, an important tool for exploring human disease.
ISSCR President Dr. Sean Morrison describes award recipients Smith and Ying as having “made enormous contributions to our fundamental understanding of pluripotency and how this knowledge can be leveraged to develop new tools that advance our understanding and treatment of human disease.”
The ISSCR Dr. Susan Lim Outstanding Young Investigator Award recognizes exceptional achievements by an ISSCR member and investigator in the early part of his or her independent career in stem cell research. The winner receives a $15,000 personal award and an opportunity to present at the ISSCR Annual Meeting. Past winners include Paul Tesar, Valentina Greco, Marius Wernig, Cédric Blanpain, Robert Blelloch, Joanna Wysocka and Konrad Hochedlinger.
Award recipient Camargo’s innovative research on adult stem cells, regulation of organ size and cancer, together with the development of a paradigm-shifting stem cell tracking technique, has greatly impacted our understanding of stem cell biology and disease, and opens new avenues in regenerative medicine, ISSCR says. His research on the Hippo signaling pathway in stem cells has provided a new understanding of the connection between the regulation of stem cells, organ growth and tumorigenesis, with implications for treating cancer and regenerative disorders.
Camargo’s development of a novel method of tracking and monitoring individual blood stem cells—and their offspring in their natural environment—opens multiple lines of scientific enquiry previously not possible, and has the potential to change our understanding of the blood system and beyond.
“The ISSCR is delighted to present our Outstanding Young Investigator Award to Fernando Camargo,” says ISSCR CEO Nancy Witty. “Dr. Camargo is an innovative young scientist, and we look forward to watching as his research transforms our knowledge of stem cell biology, disease and regeneration and to involving him in ISSCR leadership activities.”
This year marks the inaugural ISSCR Tobias Award Lecture. Supported by the Tobias Foundation, the award recognizes original and promising basic hematology research field as well as direct translational or clinical research related to cell therapy in hematological disorders. The winner receives a $15,000 personal award and presents the Tobias Lecture at the ISSCR Annual Meeting.
Inaugural award winner Zon has demonstrated longstanding scientific leadership in the fields of hematology, stem cell biology and zebrafish biology, ISSCR notes, and he has pioneered the use of zebrafish for the study of human blood formation, to identify the underpinnings of blood disorders such as leukemia and to find factors that influence blood stem cell transplantation. To probe blood stem cell biology in the zebrafish, he developed many of the techniques that are widely used today, including transplantation assays and genetic approaches, providing the basis of influential discoveries in the field by himself and others. His research has also reached into the clinic, with the discovery and development of two novel therapeutics that are now being evaluated in clinical trials for patients with leukemia and melanoma.
“Dr. Zon’s research epitomizes the bench-to-bedside impact that we strive for. His research using zebrafish demonstrates the power of model organisms to understand fundamental aspects of hematopoiesis and the ability to translate those discoveries into new therapies,” says Morrison.
ISSCR announces RFP for European co-sponsorship of the 2021 annual meeting
The ISSCR annual meeting is a cornerstone of the society. It provides a core forum for dissemination of groundbreaking research in all areas of stem cell science and translation, with participants from academic, industry, ethics and government settings worldwide. One of the society’s objectives is to choose venues for the annual meeting that reflect its international character, as well as allowing the ISSCR to highlight the contributions of the scientific community in the host region.
Currently, the practice is to hold annual meetings at venues outside of North America every third year and to alternate these meeting sites between Europe and Asia. The ISSCR board of directors has expressed the desire to hold the annual meeting in Europe in June 2021 with the support of co-sponsorship from a prominent regional stem cell community. The board has invited proposals from a local bid committee.
Important deadlines:
  • Letter of intent received by July 15, 2016
  • Full proposals will be received until Oct. 1, 2016
  • The location will be selected by the board of directors in early 2017
Focus Sessions
Focus Sessions present a symbiotic forum for industry and academic research worlds to come together for the sake of accelerating and exploring the promise of stem cell science. These sessions will kick off the annual meeting on the morning of Wednesday, June 22 June and are intended to spark rigorous discussions on topics being brought up in research labs across the globe.
All registered annual meeting attendees are encouraged to attend the Focus Sessions as part of their ISSCR 2016 registration. For the most part, they run from 9 a.m. to noon and are being held in the Moscone Center West like the rest of the meeting.
Fighting Cancer with Off-the-Shelf iPSC Immunotherapies
Presented by Fate Therapeutics
This session will provide an in-depth analysis of the recent progress, current bottlenecks and therapeutic potential of applying induced pluripotent stem cell (iPSC) technology for the development of transformative, off-the-shelf cellular immunotherapies, including engineered NK- and T-cell immunotherapies, for cancer.
This session is for scientists, clinicians, and product planning professionals interested in stem cell biology and related fields in capacities spanning basic research, translational medicine and commercialization.
Tools for Basic and Applied Stem Cell Biology
Presented by STEMCELL Technologies and Thermo Fisher Scientific
This session is organized by Stem Cell COREdinates, a consortium of human pluripotent stem cell-focused shared facilities that have joined forces to share experiences, expertise with protocols and reagents, and to establish best practices. The focus session will be divided into two sessions: First, selected COREdinates consortium member lab presentations from core facilities highlighting bioengineering, disease modeling and cell therapies and second, a panel discussion on pluripotent stem cell-based therapies.
Humanity in a Dish
Presented by WiCell Research Institute
The Next Generation Genetic Association Studies (Next Gen) program is a five-year, $80-million program to investigate functional genetic variation in humans by assessing cellular profiles that are surrogates for disease phenotypes. In this session, Next Gen consortium members will present findings on their individual cohorts, as well as analyses performed across nine studies, highlighting the impact of genetic variation on disease pathology.
A Practical Guide to Starting a Company and a Taste of the Shark Tank
Presented by the ISSCR Industry Committee
This session will provide practical tools and advice to help scientists take the leap to start their own company and will cover a range of topics: evaluating an idea and creating a plan to move it forward, navigating licensing the product, building a winning team, pitching the idea to both investors and customers and developing the product.
Ethical Implications of Genome Editing Technologies
Presented by the ISSCR Ethics Committee
This will in large part be a dialogue on the socio-ethical implications of human germline genome modification research, and will consider the relevant guidelines and legislation in different countries. Five speakers will present scientific, regulatory and ethical challenges, followed by a moderated discussion.
How EBiSC can help researchers in accessing high-quality research-grade iPSC lines
Presented by European Bank for induced pluripotent Stem Cells (EBiSC)
This session is organized by the EBiSC consortium, a three-years research project aiming to set up the not-for-profit EBiSC. Presenters will share their experience on: the establishment of an iPS cell bank with core and mirror facilities; the set-up of a robust and reliable supply chain for iPS lines including the generation of disease specific, control, gene edited and isogenic cell lines;    standardized work flows from tissue procurement to generation, characterization, preservation and supply; standardized quality control expansion; and the set-up of the ethical and legal governance structure for stem cell banking and distribution.
How Researchers Anywhere Can Use CIRM Funds to Advance Stem Cell Science
Presented by The California Institute for Regenerative Medicine (CIRM)
Over the past year CIRM has completely overhauled its funding system. It is now speedier, taking just 120 days from application to funding in hand for clinical programs. Clinical and translational researchers from all over the globe as well as basic researchers from California are invited to learn how you can partner with CIRM to advance your stem cell science, regardless of stage, toward the clinic.
ISSCR 2016 Career Fair
Thursday, June 23
Friday, June 24
9 a.m. to 5 pm.
New this year, attendees can take part in this two-day event and meet face-to-face with companies looking to hire for positions within the stem cell community. The career fair is, ISSCR says, a must-attend for those seeking career advancement opportunities, professional development resources and access to the industry’s top employers.
Workshop on Clinical Translation
Tuesday, June 21
The Workshop on Clinical Translation, held the day before the ISSCR 2016 Annual Meeting, is co-organized by the ISSCR and the American Society of Gene & Cell Therapy and will feature international experts on cellular  therapy with real-life experience moving translational projects into the clinic. Participants will gain a broad understanding of the translational process, including early-phase trials and what to consider for the longer term in taking a stem-cell based product to market. In addition, participants will have the chance to network with presenters and fellow attendees to learn more from each other’s experiences.
Who should attend
This workshop is intended for anyone, regardless of career stage, who is looking to translate their research findings to the clinic, to work or collaborate on translational projects or who has a general interest in how a treatment can emerge from biomedical research.
ISSCR endorses fetal tissue research as essential
The International Society for Stem Cell Research (ISSCR) is the world’s leading professional organization of stem cell scientists, representing more than 4,000 members in 45 U.S. states and 65 countries around the world. The ISSCR is opposed to recent efforts to inappropriately limit or prohibit biomedical research using fetal tissue. These proposals, if enacted, would obstruct critical biomedical research and inhibit efforts to improve human health. If enacted in the past, such limits would have delayed or prevented the development of therapies that have saved millions of lives.
Research using donated fetal tissue has been underway since the 1930s and has made major contributions to our understanding of biology and the development of new medical technologies. Fetal tissue is obtained from spontaneous miscarriages and legal abortions. In each case, the fetal tissue would be discarded if not donated by patients for medical research. With the consent of donors, this unique and valuable tissue can be used for research into basic biological processes and human development, as well as creating new treatments for life-threatening diseases.
Fetal tissue is an essential “gold-standard” resource that enables laboratory-based research into how human tissues and organs develop. While other approaches, such as using animal models and cells from adults, can be helpful, for some congenital and developmental conditions it is necessary to study human fetal tissues. For example, without fetal tissue research, it would not be possible to fully understand congenital defects in the heart or nervous system, and new therapies for diseases that affect these tissues would be delayed or prevented.
Further, some of the most important fetal tissue research has involved the use of fetal cell lines in developing vaccines for many diseases, including measles, mumps, rubella, chicken pox, diphtheria, tetanus, whooping cough, polio, hepatitis A, hepatitis B, rabies, shingles and adenovirus infections. Millions of lives have been saved as a result of this research. The development of the polio vaccine, which relied on the use of cultured cells from fetal tissue, has prevented hundreds of thousands of cases of polio each year and was recognized with a Nobel Prize in 1954. The April 25, 2014 U.S. Center for Disease Control and Prevention’s Morbidity and Mortality Report estimated that as a result of childhood immunizations, there were 322 million fewer illnesses, 21 million fewer hospitalizations and 732,000 fewer deaths among children born in the United States between 1994 and 2013. A great many of these lives were saved as the result of research using fetal tissue.
In addition to their historical role in vaccine development, the U.S. National Institutes of Health recognizes the use of fetal tissue in research into maternal health, premature births and infant health as “irreplaceable.” Premature infants often show delays in neural development, affecting memory, thought and language. Using fetal brain tissue, researchers have discovered that the production of new brain cells, which normally continues throughout fetal development, is impaired by premature birth. This discovery makes it possible to explore new approaches to promote normal brain cell development in premature babies. Our understanding of the causes of retinopathy of prematurity, a leading cause of blindness in premature infants, has been advanced by fetal tissue research.
Fetal tissue has also allowed researchers to test cell-based approaches to a variety of neurodegenerative diseases that do not have any other effective treatment. Clinical trials of these fetal tissue-derived cells are currently ongoing for amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease), spinal cord injury, stroke and age-related macular degeneration.
In closing, fetal tissue research has led to many new insights into human development as well as therapies that have saved millions of lives. Ongoing access to human fetal tissue that has been obtained legally and with donor consent is required to address many important questions in biomedical research and for the development of new therapies. The ISSCR endorses fetal tissue research as essential to the prevention and treatment of life-threatening diseases.
In keeping with the themes of ISSCR 2016, here are some recent news items related to stem cell work in the discovery and development arenas
Scripps Florida scientists find way to predict activity of stem cells
Method could help evaluate potential stem cell therapies for different diseases
JUPITER, Fla.—Scientists from the Florida campus of The Scripps Research Institute (TSRI) have for the first time developed a way to predict how a specific type of stem cell will act against different diseases. With more than 500 stem cell-based therapies currently in clinical trials, the findings could have an impact on evaluating these therapies and developing new ones.
The new study, published recently by the journal EBioMedicine, was led by Prof. Donald G. Phinney, acting chair of Scripps Florida’s Department of Molecular Therapeutics.
In some respects, stem cells are like coins—they have two sides. One side is their shape-shifting ability to differentiate into other types of cells; the flip side is their function, the effect they have on health and disease that underscores their therapeutic potential. For many years, Phinney noted, stem cell experts have believed that these two sides were separate and unrelated.
These new results, however, challenge that view.
“We found a coordinated link between stem cell properties and their functions,” Phinney said. “With this new information, we can begin to predict how these functions can be manipulated to make the cells more therapeutically relevant.”
Using mesenchymal stem cells, Phinney and his colleagues examined levels of a molecule known as TWIST1 in different human donor populations. They found higher levels of TWIST1 produced more angiogenic effects—boosting new blood vessel growth—while lower levels produced more anti-inflammatory and immuno-suppressive effects.
Moreover, team members were able to show that manipulating levels of TWIST1 in both cells and animal models resulted in a predictable change in stem cells’ functional attributes.
Based on their findings, the scientists developed a clinical indications prediction, or CLIP scale, which predicts the therapeutic potential of mesenchymal stem cells for a given disease indication based on their levels of TWIST1.
“There are a number of clinical trials testing mesenchymal stem cells to treat arthritis,” said Siddaraju V. Boregowda, the first author of the study and a member of the Phinney lab. “Since angiogenesis is a key part of the disease process, stem cells with high levels of TWIST1 (indicating they are more angiogenic) would not be beneficial. These cells might be helpful instead for indications such as peripheral vascular disease, where new vascularization is beneficial. The proposed CLIP scale accurately predicts these indications and contra-indications.”
In addition to Phinney and Boregowda, other authors of the study, “A Clinical Indications Prediction Scale Based on TWIST1 for Human Mesenchymal Stem Cells,” are Veena Krishnappa, Christopher L Haga of TSRI and Luis A. Ortiz of the University of Pittsburgh.
Interim results from Phase 2 Pathway study in cervical spinal cord injury
NEWARK, Calif.—StemCells Inc., a leading company in the research and development of cell-based therapeutics for the treatment of central nervous system disorders, announced recently that Dr. Stephen Huhn, the company’s chief medical officer and vice president of clinical research, presented additional details on its ongoing Phase 2 Pathway Study of HuCNS-SC cells (the company’s proprietary human neural stem cells) for the treatment of chronic cervical spinal cord injuries. 
The presentation, which took place at the 2016 American Spinal Injury Association annual meeting in Philadelphia on April 15, included a top-line update for the six patients enrolled in open-label Cohort I from the Pathway Study. The six-month results from Cohort I showed that muscle strength had improved in five of the six patients, with four of these five patients also demonstrating improved performance on functional tasks assessing dexterity and fine motor skills. In addition, four of the six patients had improvement in the level of cord injury as measured by International Standards for Neurological Classification of Spinal Cord Injury assessment. The company expects to release detailed final 12-month results on this first open-label cohort later this quarter.
“The emerging data continue to be very encouraging,” said Huhn. “We believe that these types of motor changes will improve the independence and quality of life of patients and are the first demonstration that a cellular therapy has the ability to impact recovery in chronic spinal cord injury. We currently have 13 sites in the United States and Canada that are actively recruiting patients. We have enrolled and randomized 19 of the 40 total patients in the statistically powered, single-blind, randomized controlled Cohort II. We are projecting to complete enrollment by the end of September so that we can have final results in 2017.”
The Phase 2 Pathway Study, titled “Study of Human Central Nervous System (CNS) Stem Cell Transplantation in Cervical Spinal Cord Injury,” will evaluate the safety and efficacy of transplanting HuCNS-SC cells into patients with traumatic injury of the cervical region of the spinal cord. Cohort I is an open-label dose-ranging cohort in six AIS-A or AIS-B subjects. Cohort II is a randomized, controlled, single-blinded cohort in forty AIS-B subjects. Cohort III, at the discretion of the sponsor, is an open-label arm involving six AIS-C subjects. 
The primary efficacy outcome will focus on change in upper extremity strength as measured in the hands, arms and shoulders. The trial will enroll up to 52 subjects. Enrollment of Cohort I has been completed, and the company is now enrolling patients into Cohort II.  
StemCells Inc. has demonstrated human safety data from completed and ongoing clinical studies in which its proprietary HuCNS-SC cells have been transplanted directly into all three components of the central nervous system: the brain, the spinal cord and the eye. StemCells Inc. clinicians and scientists believe that HuCNS-SC cells may have broad therapeutic application for many diseases and disorders of the CNS. Because the transplanted HuCNS-SC cells have been shown to engraft and survive long term, there is the possibility of a durable clinical effect following a single transplantation. The HuCNS-SC platform technology is a highly purified composition of human neural stem cells (tissue-derived or “adult” stem cells). Manufactured under cGMP standards, the company’s HuCNS-SC cells are purified, expanded in culture, cryopreserved and then stored as banks of cells, ready to be made into individual patient doses when needed.
Discovery might lead to fix for hereditary hearing loss
DURHAM, N.C.—A new study in STEM CELLS Translational Medicine offers people with genetic hearing loss the promise of a new therapy that just might outperform artificial cochlear implants.
Implants currently are the most effective way to treat sensorineural hearing loss, a type of hereditary hearing loss caused by genetic mutations in the hair cells—the sensory receptors of the auditory system found in the inner ear. A cochlear implant helps transfer sound to the patient’s hearing nerves and enables them to hear. But many researchers believe that stem cells could offer a more comprehensive and better fix for this problem.
“If we can find a way to correct gene mutations using stem cells it might restore the normal function of the hair cells and, thus, the patient’s hearing, too,” said Dr. Jin-Fu Wang, a lead investigator on the study conducted with colleagues at Zhejiang University, Shanghai Jiaotong University, Wenzhou Medical University in China and with those at Cincinnati Children’s Hospital Medical Center and Emory University in the United States.
In previous studies, induced pluripotent stem cells (iPSCs) derived from human adult somatic tissue such as skin and urinary cells have been generated from patients with ALS, spinal muscular atrophy, diabetes and other diseases for testing potential therapies and to correct disease-specific genes. The Wang team wanted to try this approach for sensorineural hearing loss.
They hypothesized that a protein-coding gene called MYO7A plays an important role in the assembly of stereocilia into bundles. (Stereocilia are the part of the hair cells that respond to fluid motion. Their bending is how hair cells sense sounds.) If they could use stem cells to repair the mutated MYO7A, that might result in proper growth of the stereocilia and correct the hearing loss.
The team began by generating three iPSC lines from the urinary cells of a 7-year-old hearing loss patient with compound MYO7A gene mutations, her asymptomatic father and a healthy 26-year-old female donor, respectively. The iPSC line from the 7-year-old hearing loss patient were used to correct the MYO7A mutation with CRISPR/Cas9 technique, resulting in morphologic and functional recovery of hair cell-like cells derived from the corrected iPSCs.
“The current findings confirmed our hypothesis and might provide further insight into what is behind sensorineural hearing loss. Our hope is this will facilitate the development of iPSC-based gene therapy for genetic disorders,” Dr. Min-Xin Guan, another lead investigator, concluded.
“In the future, transplantation of these functionally recovered cells may prove to be a promising therapy for deafness resulting from gene mutation,” said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and Director of the Wake Forest Institute for Regenerative Medicine. “The authors outline a variety of obstacles that must first be overcome, including finding more efficient methods to derive the large number of cells needed for treatment and developing a method to insert the cells.”
Pluristem enters into Licensing Agreement and gains key patents
HAIFA, Israel—In mid-April, Pluristem Therapeutics Inc., a leading developer of placenta-derived cell therapy products,  announced that it has entered into a licensing agreement with TES Holdings Co. Ltd., a venture company derived from the University of Tokyo, to obtain a key patent in Japan to cover the treatment of ischemic diseases with placental cell therapy rounding out the company’s intellectual property (IP) coverage.
The patent covers use of all placenta-derived mesenchymal cells that are able to produce VEGF, a signaling protein that promotes the growth of new blood vessels, which the body needs to address the damage in ischemic tissue in the heart, brain, skeletal muscle, or elsewhere in the body. The patent is valid through 2023 and may be eligible for up to five years of patent term extension.
Akio Hayashi, President of TES Holdings, which manages the commercialization of this IP, commented, “Placenta-derived cell therapies may significantly improve the health and wellbeing of millions of people who suffer from ischemic disease. We are pleased that Pluristem, which is a leading player in the world’s regenerative medicine space, has licensed this patent because their unique experience with placental cell therapies make them optimally positioned to use knowledge developed at the University of Tokyo which demonstrates Japan’s strong capabilities in this space. We hope that this cooperation will advance the regenerative medicine industry and benefit the people with unmet medical needs.”
“The University of Tokyo is well known in for its cutting edge research in the field of cell therapy, and we are happy to expand our cooperation with this world class academic institution.  As we prepare to initiate a clinical trial in critical limb ischemia targeting conditional marketing approval via Japan’s new accelerated regulatory pathway for regenerative medicine, our patents addressing placental cell therapies remain a core asset and important to our current negotiations with large pharmaceutical companies regarding potential partnerships in Japan,” stated Pluristem Chairman and CEO Zami Aberman.
This license news follows Pluristem’s recent announcement that the Japan Patent Office granted the Company two key patents addressing three-dimensional methods for expanding placental and adipose cells, and specified cell therapies produced from placental tissue using these methods.
“These latest patent grants in Japan fortify our intellectual property position globally, and specifically in the Japanese market, where we are in active negotiations with potential pharmaceutical partners,” stated Aberman of that news. “Our proprietary process and technology for growing placenta-derived cells within a 3D microenvironment make large scale, cost effective cell therapy production a reality, and IP protection of these methods in Japan is a key asset. The use of these cells to treat disorders of the hematopoietic system is an important indication for PLX cells that is now protected in Japan.”
iPSC used to study molecular mechanisms in dilated cardiomyopathy
Current drug therapies for cardiovascular disease alleviate symptoms for only 50 to 70 percent of patients, often with unwanted side effects. As a result, there is a pressing need for better treatment options. Induced pluripotent stem cells (iPSCs) are a promising new field of medical research yielding novel insights into the molecular mechanisms of heart disease, and researchers at Stanford University in California hope that their iPSC studies will produce better cardiovascular disease models and lead to new patient-specific therapies and screening approaches for drugs.
Dr. Elena Matsa is using iPSCs for studying cardiovascular disease within a wider research remit looking at biological mechanisms of adult stem cells, embryonic stem cells, and iPSCs. The lab uses a combination of next generation sequencing, tissue engineering, physiological testing, and molecular imaging technologies in its research.
For the last year, Dr. Matsa has been using Qlucore’s Omics Explorer software to analyze data from experiments that use iPSCs to study dilated cardiomyopathy (DCM), a fatal heart disease that affects 5 in 100,000 adults.
DCM is the third leading cause of heart failure in the US. It has various causes, one of which is mutations in genes involved in sarcomeric proteins in the heart muscle, which make the heart muscle baggy and thin so it can no longer pump blood efficiently.
For the DCM studies, the lab works closely with cardiologists to find genetically affected patients at their heart clinics. Heart muscle cells (cardiomyocytes) are collected from these individuals if they have heart surgery. iPSCs are made from “reprogrammed” skin or blood cells from the same patients and then turned into beating heart muscle cells for direct comparison. It takes six to 12 months and several thousands of dollars to generate the cells and sequencing data for these experiments.
Since the technique for making iPSCs is relatively new (John B. Gurdon and Shinya Yamanaka received the Nobel prize for the work in 2012), one aim of the DCM research is to assess whether ‘lab-made’ heart cells are a good representation of equivalent adult human cells.
A second goal is to see how both cell types respond to various drugs used to treat DCM in the clinic. “If the two types of heart cell respond similarly, it means we can potentially do pre-clinical drug tests on iPSC cardiomyocytes confident that the results will accurately predict how the real human heart will react to a new drug before it is released on the market,” explains Matsa.

Subscribe to Newsletter
Subscribe to our eNewsletters

Stay connected with all of the latest from Drug Discovery News.

DDN Magazine May 2024

Latest Issue  

• Volume 20 • Issue 3 • May 2024

May 2024

May 2024 Issue