The Stem Cell Report with Janet Rossant – Details, episodes & analysis

Those who study neurological diseases and their underlying cellular and molecular mechanisms have a number of scientific models at their disposal. In vivo animal models, particularly those bearing targeted genetic modifications, remain the gold standard, especially when it comes to assessment of behavioral readouts and neurobiological disease mechanisms in vivo. Historically, animal models have been widely used for preclinical validation of drug efficacy and safety. 

Increasingly there is a move away from this approach, and human cellular models using induced pluripotent stem cells and their derivatives such as three-dimensional organoid models have recently provided unprecedented genetic and mechanistic insights into disease mechanisms. Human/animal chimeras made by xenografting human cells into the animal brain have unparalleled potential to study human cells in the context of the whole organism. Our guests today review the use of these types of model systems to understand neuropsychiatric diseases, focusing on Alzheimer’s and Parkinson’s disease, epilepsy, Down syndrome, and schizophrenia and provide critical appraisal of the impact of human-rodent xenografting approaches for advancing our understanding of those diseases and brain development.

Host
Martin Pera, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
@martinperaJAX

Guests
Giuseppe Testa, MD, PhD, Università Statale, Human Technopole, and the European Institute of Oncology, Italy

Marlene Pereira, PhD UCB Pharma, Brussels, Belgium

Reinald Shyti, PhD, Human Technopole and the European Institute of Oncology, Italy

Supporting Content
In and out: benchmarking in vitro, in vivo, ex vivo and xenografting approaches for an integrative brain disease modeling pipeline, Stem Cell Reports

About Stem Cell Reports
Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians.
Twitter: @StemCellReports

About ISSCR
With nearly 5,000 members from 75+ countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.

ISSCR Staff
Keith Alm, Chief Executive Officer
Yvonne Fisher, Managing Editor, Stem Cell Reports
Kym Kilbourne, Director of Media and Strategic Communications
Jack Mosher, Scientific Advisor

Voice Work
Ben Snitkoff

This episode of The Stem Cell Report will discuss the process of directing stem cells to acquire the proper identity, an essential step in the development of effective and durable cell replacement therapies. Specifically, we will talk about the process of directing cells into a ventral mesencephalic dopaminergic fate for treating Parkinson’s disease. 

Guests
Agnete Kirkeby is an Associate Professor in the Department of Neuroscience at the University of Copenhagen, a Principal Investigator with the Novo Nordisk Foundation Center for Stem Cell Medicine renew, and a Principal Investigator at the Wallenberg Center for Molecular Medicine at Lund University. Professor Kirkeby led the preclinical development of a stem cell-based therapy for Parkinson’s Disease which was approved for a first-in-human clinical trial in Sweden. Agnete also co-chairs the ISSCR 2024 Annual Meeting Program Committee, the group responsible for planning the upcoming meeting this July in Hamburg, Germany. 

Pedro Rifes received his PhD from the Universidade de Lisboa in Portugal and was a postdoctoral scholar in the Kirkeby Laboratory. He served as an Adjunct Assistant Professor at the University of Copenhagen and is currently a Project Manager at Bioneer A/S, a Danish specialty Contract Research Organization.  Connect with him on LinkedIn.

Host
Martin Pera, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
@martinperaJAX

Supporting Content
Paper link: Forced LMX1A expression induces dorsal neural lolfates and disrupts patterning of human embryonic stem cells into ventral midbrain dopaminergic neurons, Stem Cell Reports

 About Stem Cell Reports
Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports  focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. X: @StemCellReports

About ISSCR
With nearly 5,000 members from 75+ countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.

ISSCR Staff
Keith Alm, Chief Executive Officer
Yvonne Fisher, Managing Editor, Stem Cell Reports
Kym Kilbourne, Director of Media and Strategic Communications
Jack Mosher, Scientific Advisor

Voice Work
Ben Snitkoff 

Over the last 10 years of Stem Cell Reports, the journal has published nearly 2,000 papers across the breadth of stem cell research. In this special episode of the podcast, we are celebrating the anniversary of the journal by talking with the authors from some of the most highly cited publications in the journal's history.

The guests on this episode of the podcast have collective expertise that makes them the “dream team” of muscle stem cell biology and its application to treat disease.  

 Akitsu Hotta is a Principal Investigator and Associate Professor in the Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University and was the recipient of the 2020 Japanese Society for Regenerative Medicine Award. His laboratory published the 2015 paper, Precise correction of the dystrophin gene in Duchenne muscular dystrophy patient induced pluripotent stem cells by TALEN and CRISPR-Cas9. 

Thomas Rando is the Director of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Biology at the University of California Los Angeles, where he is also Professor of Neurology and of Molecular, Cell and Developmental Biology. Dr Rando is a board-certified neurologist and a member of the National Academy of Medicine and a member of the American Academy of Arts and Sciences. He is also the 2023 recipient of the ISSCR Achievement Award, which recognizes the transformative body of work of an investigator that has had a major impact on the field of stem cell research or regenerative medicine. His laboratory published the 2015 paper, entitled, the Ex vivo expansion and in vivo self-renewal of human muscle stem cells. 

April Pyle is an Associate Professor in the Department of Microbiology, Immunology and Molecular Genetics at the University of California Los Angeles and a member of the Eli and Edythe Broad Stem Cell Center, the Center for Duchenne Muscular Dystrophy, and the Jonsson Comprehensive Cancer Center at UCLA. She is also an Associate Editor of Stem Cell Reports.

Host
Martin Pera, PhD, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
Twitter: @martinperaJAX

About ISSCR
With more than 4,600 members from 75+ countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.

ISSCR Staff
Keith Alm, Chief Executive Officer
Yvonne Fisher, Managing Editor, Stem Cell Reports
Kym Kilbourne, Director of Media and Strategic Communications
Jack Mosher, Scientific Advisor

Voice Work
Ben Snitkoff

Human pluripotent stem cells have an unlimited capacity to self-renew in culture. This feature, along with their ability to become any cell type in the adult body, makes them a unique tool to study human biology in health and disease. Unfortunately, human pluripotent stem cells have a propensity to acquire genetic abnormalities in culture that may limit their scientific and clinical use.

Among the most prevalent genomic changes found in pluripotent stem cells are various forms of over-representation of sequences on the long arm of chromosome 20, with up to 20% of tested cultures containing such an aberration. One such anomaly, the isochromosome 20 mutation, is also found in amniocentesis analyses. 

In  this episode, Martin Pera is joined by three scientists, who along with their colleagues, authored the recent paper published in Stem Cell Reports entitled, The isochromosome 20q abnormality of pluripotent cells interrupts germ layers differentiation.  This publication explores the effects of this particular anomaly on the ability of pluripotent stem cells to differentiate both spontaneously and by directed differentiation.  The results were surprising, with implications for understanding early development and the potential therapeutic use of pluripotent stem cells. The authors  also discuss some of the challenges of working with pluripotent stem cells.

Guests
Ivana Barbaric, PhD, University of Sheffield, UK
Pete Coffey, PhD, University College London and the University of California, Santa Barbara, US
Loriana Vitillo, PhD, University College London, UK

Host
Martin Pera, PhD, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
Twitter: @martinperaJAX

Supporting Content
The isochromosome 20q abnormality of pluripotent cells interrupts germ layer differentiation, Vitillo, et. al., Stem Cell Reports (2023)

About Stem Cell Reports
Stem Cell Reports is the open access journal of the ISSCR for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. Twitter: @StemCellReports

About ISSCR
With more than 4,600 members from 75+ countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.

ISSCR Staff
Keith Alm, Chief Executive Officer
Yvonne Fisher, Managing Editor, Stem Cell Reports
Kym Kilbourne, Director of Media and Strategic Communications
Jack Mosher, Scientific Advisor

Voice Work
Ben Snitkoff

The PiWi family of genes may have a diminutive sounding name, but they have a large role in the function of the germline and germline stem cells. Initially discovered in Drosophila, these highly conserved RNA-binding proteins have well-established roles in the regulation of spermatogenesis and germ stem cell maintenance, in addition to silencing transposable elements. However, PiWi function outside of the germline is relatively unexplored. New findings from the Lin laboratory show that Drosophila Piwi has a role in intestinal homeostasis where it functions to establish intestinal stem cells, maintain the enteroblast lineage, and support of the enterocytes. It also has a role in silencing retrotransposons of the gut. Collectively, these intestinal roles of PiWi are critical to organismal longevity as the loss of PiWi leads to a shortened lifespan in the fly.
 
Martin Pera is joined by scientists Drs. Haifan Lin and Xiongzhuo Tang. Dr. Lin is the Eugene Higgins Professor of Cell Biology and the Founding Director of the Yale Stem Cell Center. Among his many achievements, Haifan is a member of US National Academy of Sciences, a member of American Academy of Arts and Sciences, and a Foreign Member of Chinese Academy of Sciences. He is currently the president of the ISSCR. 

Xiongzhuo Tang was a postdoctoral fellow in the Lin laboratory and is now a professor in the Animal and Nutritional Genome and Germplasm Innovation Research Center in the College of Animal Science and Technology at the Hunan Agricultural University in Hunan China.

Drs. Lin and Tang are authors of the recent paper published in Stem Cell Reports entitled, Piwi maintains homeostasis in the Drosophila adult intestine.

Guests
Haifan Lin, PhD, Yale University
Xiongzhuo Tang, PhD, Hunan Agricultural University

Host
Martin Pera, PhD, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
Twitter: @martinperaJAX

Supporting Content
Piwi maintains homeostasis in the Drosophila adult intestine, Tang, et al., Stem Cell Reports (2023)

About Stem Cell Reports
Stem Cell Reports is the open access journal of the ISSCR for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. Twitter: @StemCellReports

About ISSCR
With more than 4,600 members from 75+ countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.

ISSCR Staff
Keith Alm, Chief Executive Officer
Yvonne Fisher, Managing Editor, Stem Cell Reports
Kym Kilbourne, Director of Media and Strategic Communications
Jack Mosher, Scientific Advisor

Voice Work
Ben Snitkoff

This episode is sponsored by Bio-Techne.

While advances in stem cell science have led to an increasing number of stem cell-based therapies entering clinical trials, the field is still relatively immature. Thus, these first-in-human trials are using pioneering approaches unique unto themselves, leaving scientists, physicians, and regulators to assess the best approaches for a specific therapy and/or disease.  In this episode of the podcast, Martin Pera is joined by physician-scientists Roger Barker and Rajesh Rao who have and are leading stem cell-based trials to discuss some of the critical aspects of the process and reflect on the “lessons learnt” during their translational journey.  

Roger Barker, a pioneer in developing cell therapies for Parkinson’s disease, is a Professor of Clinical Neuroscience at the University of Cambridge and Consultant Neurologist at the Addenbrooke’s Hospital Cambridge. He is a Principal Investigator in the Medical Research Council (MRC) – Wellcome Trust Stem Cell Institute in Cambridge and Director of the MRC-funded UK Regenerative Medicine Platform Stem and Engineered Cell Hub. Roger is a current ISSCR Board Member, former chair of the ISSCR’s Clinical Translation Committee and a Fellow of the Academy of Medical Sciences.

Rajesh Rao is an ophthalmologist and the Leonard G Miller Professor of Ophthalmology & Visual Sciences at the University of Michigan; Director of Retina Service at VA Ann Arbor Health System; and the Leslie H. and Abigail S. Wexner Emerging Scholar at the A. Alfred Taubman Medical Research Institute. Dr. Rao is currently running a cell replacement therapy for macular degeneration and is the current chair of the ISSCR’s Clinical Translation Committee.

Guests
Roger Barker, MBBS, PhD, University of Cambridge, UK
Rajesh Rao, MD, University of Michigan, USA

Host
Martin Pera, PhD, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
Twitter: @martinperaJAX

Supporting Content
Lessons learnt, and still to learn, in first in human stem cell trials, Barker et al, Stem Cell Reports (2022)

About Stem Cell Reports
Stem Cell Reports is the open access journal of the ISSCR for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. Twitter: @StemCellReports

About ISSCR
With more than 4,600 members from 75+ countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.

ISSCR Staff
Keith Alm, Chief Executive Officer
Yvonne Fisher, Managing Editor, Stem Cell Reports
Kym Kilbourne, Director of Media and Strategic Communications
Jack Mosher, Scientific Advisor

Voice Work
Ben Snitkoff

This episode is sponsored by Bio-Techne.

Computational approaches have become integral to understanding biological processes, in part because of a need to come to grips with the enormous amounts of high dimensional data that we generate using our current tools for cellular analysis. This is especially relevant for stem cell and developmental biology where development, disease modeling, regulatory networks, and lineage formation all lend themselves to the combination of experimental and computational methods. Today’s program explores how computational biology approaches can be used to understand and model early development, specifically the lineage commitment of the early embryo and its broader application to enhance the engineering of cell differentiation strategies.

 Martin Pera is joined by bioengineers Peter Zandstra and Himanshu Kaul. Dr. Zandstra is one of the early pioneers in the application of engineering principles to study stem cell biology and is a Professor in the School of Biomedical Engineering and the Michael Smith Laboratories at the University of British Columbia. He has received numerous honors and awards including being named the Canada Research Chair in Stem Cell Bioengineering and he is a fellow of the Royal Society of Canada. Dr. Kaul is a Royal Academy of Engineering Research Fellow in the School of Engineering and Department of Respiratory Sciences and a new group leader at the University of Leicester.

Host
Martin Pera, PhD – Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
Twitter: @martinperaJAX

Guests
Peter Zandstra, PhD, University of British Columbia, Vancouver, BC, Canada
Himanshu Kaul, PhD,  University of Leicester, Leicester, UK

Supporting Content
Virtual cells in a virtual microenvironment recapitulate early development-like patterns in human pluripotent stem cell colonies 

About Stem Cell Reports
Stem Cell Reports is the Open Access journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians.
Twitter: @StemCellReports

About ISSCR
With more than 4,600 members from 75+ countries, the International Society for Stem Cell Research is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.
Twitter: @ISSCR

Acknowledgements

ISSCR Staff
Keith Alm, Chief Executive Officer
Yvonne Fisher, Managing Editor, Stem Cell Reports
Kym Kilbourne, Director of Media and Strategic Communications
Jack Mosher, Scientific Advisor

Voice Work
Ben Snitkoff

Music
@Konovalov

This episode of The Stem Cell Report will explore the scientific applications, advances, and challenges of interspecies chimeras – organisms consisting of cells from at least two different species. The development of interspecies chimeras, most recently advanced by the discovery of pluripotent stem cells and enhancements in genetic editing, have led to greater understanding of fundamental developmental and biological concepts, insight into evolution, and even the development of potential regenerative approaches for human health. Martin Pera will be joined by Drs. Ori Bar-Nur and Jun Wu, along with Joel Zvick, next generation scientists who are pioneering advances in interspecies chimera research.

Host
Martin Pera, PhD – Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
Twitter: @martinperaJAX

Guests
Ori Bar-Nur, PhD, ETH Zurich, Switzerland
Joel Zvick, ETH Zurich, Switzerland 
Jun Wu, PhD, UT Southwestern, USA

Supporting Content
Exclusive generation of rat spermatozoa in sterile mice utilizing blastocyst complementation with pluripotent stem cells, Stem Cell Reports, 2022

About Stem Cell Reports
Stem Cell Reports is the Open Access journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians.
Twitter: @StemCellReports

About ISSCR
With 4,500 members from more than 70 countries, the International Society for Stem Cell Research is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.
Twitter: @ISSCR

Acknowledgements

ISSCR Staff
Keith Alm, Chief Executive Officer
Yvonne Fisher, Managing Editor, Stem Cell Reports
Kym Kilbourne, Director of Media and Strategic Communications
Jack Mosher, Scientific Advisor

Voice Work
Ben Snitkoff

Music
@Konovalov

In this episode of The Stem Cell Report, sponsored by Bio-Techne, we will explore the modeling of complex human neuropsychiatric diseases such as autism, bipolar disorder, and others using stem cell-based, three-dimensional culture models of the brain and its development. Martin Pera will be joined by Drs. Carol Marchetto and Rusty Gage, experts in the normal and pathological development of the brain. Carol Marchetto is an Assistant Professor in the Anthropology Department at the University of California, San Diego and an adjunct Assistant Professor at the Salk Institute. Rusty Gage is the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Disease and the President of the Salk Institute for Biological Studies. He has received numerous awards and recognition for his research including his appointment as a Fellow of the National Academy of Medicine. He is a former president of the ISSCR and a current member of the Stem Cell Reports Editorial Board.

Host
Martin Pera, PhD – Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
Twitter: @martinperaJAX

Guests
Carol Marchetto, PhD, University of California, San Diego, USA
Rusty Gage, PhD, Salk Institute for Biological Studies, USA  

Supporting Content

Reaching into the toolbox: Stem cell models to study neuropsychiatric disorders
Ethical, Legal, and Regulatory Issues Associated with Neural Chimeras and Organoids

About Stem Cell Reports

Stem Cell Reports is the Open Access journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians.
Twitter: @StemCellReports

About ISSCR
With nearly 4,500 members from more than 70 countries, the International Society for Stem Cell Research is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.
Twitter: @ISSCR

Acknowledgements

ISSCR Staff
Keith Alm, Chief Executive Officer
Yvonne Fisher, Managing Editor, Stem Cell Reports
Kym Kilbourne, Director of Media and Strategic Communications
Jack Mosher, Scientific Advisor

Voice Work
Ben Snitkoff

Music
@Konovalov

To celebrate the ISSCR’s 20th anniversary, Martin Pera is joined by three members of the ISSCR Board of Directors; Fiona Doetsch (Biozentrum at the University of Basel, Switzerland), Clerk of the ISSCR, Takanori Takebe (Cincinnati Children's Hospital Medical Center, USA/Tokyo Medical and Dental University and Yokohama City University, Japan) is a Director, and Leonard Zon (Boston Children’s Hospital, USA) is an Ex Officio member, past president, and founder of the ISSCR. In addition to running their own laboratories these scientists are part of the ISSCR leadership and will talk about the ISSCR’s history, impact, the recent meeting, and the Society’s future. 

Guests
Fiona Doetsch, PhD, University of Basel, Switzerland
Takanori Takebe, MD, PhD, Cincinnati Children’s Hospital, USA and Institute of Research, Tokyo Medical and Dental University, Japan
Leonard Zon, MD, Boston Children’s Hospital, USA and Harvard Stem Cell Institute, USA

Host
Martin Pera, PhD – Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
Twitter: @martinperaJAX

Supporting Content
ISSCR Website
Stem Cell Reports
ISSCR 2022

About Stem Cell Reports
Stem Cell Reports is the Open Access journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians.
Twitter: @StemCellReports

About ISSCR
With nearly 4,000 members from more than 65 countries, the International Society for Stem Cell Research is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.
Twitter: @ISSCR

Acknowledgements

ISSCR Staff
Keith Alm, Chief Executive Officer
Yvonne Fisher, Managing Editor, Stem Cell Reports
Kym Kilbourne, Director of Media and Strategic Communications
Jack Mosher, Scientific Advisor

Voice Work
Ben Snitkoff

Music
@Konovalov