Anders Björklund is senior professor of neuroscience at the Wallenberg Neuroscience Center at Lund University in Sweden. He is a pioneer in the study of reparative and neuroprotective mechanisms in the CNS using neural transplantation and gene transfer methods. In the 1980s Björklund´s team led the development of techniques for brain circuitry reconstruction in rodent models of neurodegenerative diseases, leading to the development of the approach used for dopamine cell replacement in patients with Parkinson´s disease. The Lund neural transplantation program has since the 1980s been a leader in the development of dopamine cell replacement therapy for Parkinson´s disease. Current research at the Lund center is focused on the development and refinement of protocols for the generation of transplantable midbrain dopamine neurons from pluripotent stem cells. An exploratory clinical trial using ESC-derived dopamine neurons, StemPD, was initiated by the Lund team in 2013.

Cell replacement therapy for Parkinson's disease is based on the idea that dopamine neuron progenitors derived from pluripotent stem cells can be used to replace the nigral dopamine neurons that have been lost to the disease. In this lecture I will summarize the state of the art in this field, how we got to here, and how the dopamine cell replacement approach can be further refined and developed to reach the goal of fully functional circuitry repair.

Prof. Jacob (Yaqub) Hanna is pioneering techniques in induced pluripotency from adult cells and synthetic whole embryo models made solely from Induced pluripotent stem (iPS) cells in the petri dish without using sperm, egg or uterus. He was the first to expand prolonged periods of normal mammalian embryo development in an “artificial uterus” environment. The latter enabled him to be the first to generate advanced stage whole synthetic embryos made entirely from naïve iPS cells in the petri dish, that can demonstrate organ formation. He adapted these approaches to derive the first complete human embryo-like model equivalent to day 14. He received numerous awards including the Rappaport Prize in biomedical research, a Krill Prize by the Wolf Foundation, the Kimmel Award and in 2021 was ranked at the top of the list of 50 leading world thinkers by Prospect magazine.

Anne is Professor of Clinical Neuroscience at Cardiff University and Honorary Consultant Neurologist at the University Hospital of Wales. She undertook her medical training and PhD at Cambridge University and completed specialist training at the National Hospital for Neurology in London and Addenbrookes hospital in Cambridge. She moved to Cardiff in 2001, where she directs the Cardiff University Brain Repair Group and co-directs the Wales B.R.A.I.N. Unit, which aims to deliver therapeutics into the brain in neurological conditions. She has a special interest in regenerative medicine, especially with respect to the neurodegenerative condition Huntington’s disease, and she is current chair of the European Huntington’s disease Network.

A key target donor cell for cell therapy in Huntington's disease (HD) is the striatal medium spiny neuron (MSN). Along with collaborators in the Repair-HD consortium, we developed a human pluripotent stem cell-derived MSN progenitor product, which we are now progressing towards a first-in-man clinical trial. However, there are multiple challenges along the translational pipeline, including authenticity of the differentiated cell product, cell delivery strategies, and designing efficient clinical trials. As part of the international translational network, SC4HD, we aim to address these challenges, many of which are common to a range of donor cell types and diseases.

Hideyuki Okano, a trailblazer in regenerative medicine, began his career with an M.D. from Keio University in 1983, followed by a Ph.D. in 1988. His postdoctoral work at Johns Hopkins University paved the way for professorships at Tsukuba, Osaka, and Keio Universities, where he focused on neural stem cells, iPS cells, and spinal cord injury research. Okano's groundbreaking work has earned him international recognition, including the Purple Ribbon Medal and the Erwin von Bälz Prize. As of 2024, he continues his research as a distinguished professor at Keio University and a visiting professor at Fujita Health University. Additionally, he serves as the Vice President of the International Society for Stem Cell Research (ISSCR), contributing significantly to the global advancement of stem cell research and regenerative medicine, showcasing his commitment to both scientific innovation and ethical research practices.

We have been developing the transplantation of allogeneic iPSC-derived neural stem/progenitor cells (NS/PCs) into patients with complete Spinal Cord Injury (SCI) in subacute phase. In our clinical trial, we designed to transplant approximately 2 million iPSC-NS/PCs for 4 patients with complete subacute SCI patients into the injury's epicenter (UMIN000035074). In December 2021, we performed the surgery of cell transplantation for the first participant. The surgery was successfully completed. In November 2023, we completed the recruitment and surgeries of all 4 patients required for this First-in-Human clinical study. Treatment-related serious adverse effects are not observed at this point.

Dr. Malin Parmar is a professor in Cellular Neuroscience at Lund University in Sweden, a Distinguished Professor of the Swedish Research Council and a New York Stem Cell Foundation Robertson Investigator. Together with her lab she has made significant discoveries on how human fibroblasts can be converted into neurons, how glial cells can be reprogrammed into neurons in vivo, and how functional dopamine neurons can be generated from human embryonic stem cells. Her research has a strong translational focus and she leads the European trial STEM-PD, a first in human clinical trial using stem cell-derived dopamine neurons to treat Parkinson’s Disease. She is a member of the Swedish Royal Academy of Science and a member of the executive board for International Society for Stem Cell Research (ISSCR).

Cell based transplantation aimed at the replacement of lost dopamine (DA) neurons holds great potential for the treatment of Parkinson’s disease (PD) and clinical trials have been initiated at several centers around the world. We have used single cell RNA sequencing (scRNAseq) to profile the developmental trajectory from pluripotency to different types of therapeutic cells in vitro and also to map the graft composition after transplantation into xenograft models of PD. In more recent studies we have integrated barcode linage tracing and retrograde transport to experimentally address lineage diversification as well as to link molecular DA subtype identity with function and integration. These data will serve as the foundation to develop second generation stem cell derived DA neurons for cell therapy in PD

Michael began research in spinal cord injury during his undergraduate research at the University of Tasmania. After graduating, Michael then completed his PhD with Norman Saunders at the University of Melbourne. In 2005, he began postdoctoral training at the Universities of Melbourne and then Florida, before being promoted to faculty in 2009. Michael accepted a position with the Spinal Cord Research Center at Drexel University in 2013, to continue his research into spinal cord injury, neuroplasticity and strategies to optimize repair and lasting functional recovery. Now a tenured Associate Professor, funded by the NIH and research foundations, Michael is actively pursuing cell therapies and rehabilitative strategies to promote recovery after cervical spinal cord injury.
http://www.spinalrepair.org/cover-page/

After a BSc in Human genetics (University of Leeds), an MSc in Neuroscience (University of Edinburgh), a PhD (University College of London) and a post-doc at the Institute of Child Health, I joined the CEA in France where I was hired as head of the primate Neurosurgery and Behavioural platforms in the Molecular Imaging research Center (MIRCen). I was appointed deputy director (2019) and then director of MIRCen in 2023. I have led over 40 projects involving primates and have extensive expertise in the design and execution of pre-clinical protocols for brain delivery of drugs, viral vectors and cells, as well as in the assessment of cognitive and motor functions. I was appointed president of NECTAR in 2021 and I co-lead the EHDN Advanced therapies working group. I am a member of the steering committee of the Inernational Stem Cells for Huntington's disease consortium and of the GDR BioSimia.

In the spectrum of neurodegenerative disorders, proteinopathies are characterized by intracellular and/or extracellular abnormal protein aggregation. Many decades of research have. Cellular and engineered animal models have been instrumental in identifying aggregate composition, localization and propagation dynamics. While no animal model completely replicates human diseases like Alzheimer's, Parkinson's, or Frontotemporal Dementia, they can mimic initial protein aggregation or other key pathological features and continue advancing our understanding of the mechanisms behind brain dysfunction and degeneration. Through this talk I would like to discuss the opportunities for pathological and therapeutic exploration of two engineered primate models of tauopathy and synucleionpathy.

Xiaoqing Zhang is a Professor in School of Medicine, Tongji Univesity, Shanghai. He obtained his PhD from Fudan University, Shanghai, and then had his postdoctoral training in Dr. Su-Chun Zhang’s lab in Waisman Center, University of Wisconsin-Madison. Dr. Xiaoqing Zhang’s research focus is human neural development and cell-based thearapy for neurological disorders. With integrated platforms of human embryonic stem cell neural differentiation, genetic engineering, brain organoid culture and human smaples, he has uncovered that human neuroectoerm development shows an evolutionarily novel trait, which leads to an “activation-transformation” model for human dorsal-vental regional patterning. His recent researches have also established sophisticated technologies for non-invasive survey and remote controls of brain allografts, and “off-the shelf” strategies for immunocompatible cell transplantation through genetic engineering in pluripotent stem cells.

Cell or organ transplantation is the most promising option to treat degenerative diseases and organ failure, while allogeneic immune rejection remains a major barrier for the clinical translation of these therapies. We engineered both donor cells and immune selection environments in the recipient thymus for immunocompatible cell or organ transplantation. The engineered hypoimmunogenic human pluripotent stem cells via the expression of membrane-bound and secreted β2m-HLA-G fusion proteins could serve as an unlimited cell source for generating universally compatible "off-the-shelf" cell grafts, and the designed thymus vaccination strategy could induce T cell tolerance to exposed donor MHC for allogeneic organ transplantation.

Kah-Leong Lim is Professor and Associate Vice President of Research at the NTU President's office as well as Director of the Neuroscience and Mental Health Programme at the NTU-Lee Kong Chian School of Medicine, where he is also the President's Chair in Translational Neuroscience. He is a Visiting Professor at the Department of Brain Sciences, Imperial College London (UK) and a Distinguished Visiting Academic at the National Neuroscience Institute (Singapore).

Dr Lim obtained his PhD from the Singapore Institute of Molecular & Cell Biology in 1999, and thereafter did his postdoctoral training in Harvard Medical School and Johns Hopkins Medicine. His laboratory works on neuroprotective and neurorestorative strategies for Parkinson's disease. For his research, he has received numerous awards including the Singapore Neuroscience Association Distinguished Neuroscientist Award and the (Singapore) President Science Award (Team) in 2018.

Parkinson's disease (PD) is a prevalent neurodegenerative disease that remains incurable. With the advent of induced pluripotent stem cell (iPS) technology, regenerative therapy using iPS cells for PD has now become a reality. However, the significant cost of autologous transplantation, and the need for immunosuppression regiment for allogenic approach represent barriers to the routine use of iPS-based therapy in the clinic. In this talk, I will share our recent work on the establishment and use of human umbilical cord lining-derived iPS cells (termed “CLIPS”) as a genetically unmodified, naturally occurring hypo-immunogenic source of cells for regenerative therapy for PD.

Hongkui Deng, is a Boya Chair Professor and Senior Investigator of the Center for Life Sciences at Peking University. He is also Department Chair of Cell Biology at School of Basic Medical Sciences of Peking University Health Science Center. Since 2013, he has been the director of the Peking University Stem Cell Research Center. Professor Deng’s research focuses on somatic cell reprogramming and lineage specific differentiation of human pluripotent stem cells. In 2013, his lab developed a chemical reprogramming strategy to induce pluripotent stem cells from somatic cell types using only small molecules. This breakthrough has opened new avenues for manipulating cellular states or identities via chemical reprogramming, and his lab has recently applied this chemical approach in promoting tissue regeneration in vivo.

Chemical reprogramming offers an unprecedented opportunity to control somatic cell fate and generate desired cell types – including pluripotent stem cells – in a precise, flexible, and controllable manner. Recent success in the chemical reprogramming of human somatic cells by activating a regeneration-like program provides an alternative way of producing stem cells for clinical translation. Likewise, chemical manipulation enables acquisition of multiple (stem) cell states, ranging from totipotency to the stabilization of somatic fates in vitro. Here, I will present our progress in using chemical approaches for cell fate manipulation, in addition to future opportunities in this promising field.

Professor Jihwan Song earned his D.Phil. from the University of Oxford in 1995, majoring in developmental biology. After completing his postdoctoral training at MIT, Harvard Medical School, and others, he established his own lab in the Department of Biomedical Science at CHA University in Korea in 2000. In addition to his academic roles, he has served as the past President (2021) and Chairman (2022) of the Korean Society for Stem Cell Research (KSSCR) and currently holds the position of Director of the Global Alliance for iPSC Therapies (GAiT) and the Asian Alliance for Stem Cells and Regenerative Medicine (AASCRM). He is also a member of the MCTR and MIOC Committees of the International Society for Stem Cell Research (ISSCR). Professor Song's research primarily focuses on developing cell therapy for challenging neurodegenerative diseases such as Huntington's disease, using HLA-homozygous induced pluripotent stem cells (iPSCs), as well as conducting drug screening using iPSC-derived neural cells from patients with Alzheimer's disease, etc. In 2019, Professor Song founded a start-up company called iPS Bio, Inc., to advance the clinical application and commercial development of his research outcomes.

Lyandysha Zholudeva, PhD is a Research Investigator at the Gladstone Institutes in San Francisco, CA, USA. Her research team is focused on leveraging the advances in human stem cell engineering to differentiate specific populations of human interneurons that can be used for therapeutic purposes after CNS injury or disease. Currently, the team's efforts are centered on pioneering techniques to restore motor, sensory, and autonomic functions following spinal cord injuries. Furthermore, the lab is exploring the potential of these innovations to treat non-traumatic injuries and degenerative diseases, overall broadening the impact of the work.

Advances in cell therapies offer new promise for severe neural injuries like spinal cord injury (SCI). One particular type of neuron – the spinal V2a interneuron – has been implicated as a key component in plasticity and therapeutically driven recovery post-SCI. Our lab engineers these interneurons from human induced pluripotent and embryonic stem cells, testing their ability to form functional synapses with injured motor, sensory, and autonomic networks. Using clinically relevant contusion SCIs in adult rats, we aim to repair neural damage with transplanted cells. We used spinal V2a-enriched interneurons to repair the phrenic motor network, assessing synaptic integration with neuroanatomical tracers, optogenetics, and characterized transplanted cells prior to and post-transplantation with RNA sequencing. This strategy significantly improves diaphragm muscle activity, showing great promise for motor recovery post-SCI.

Dr. Svendsen's lab has been sing induced pluripotent stem cells to both model and treat human diseases for the past decade.

We have developed a novel combined fetal neural cell progenitor and GDNF product (CNS10-NPC-GDNF) to protect both motor and dopamine neurons in ALS and Parkinson's. Updates on pre-clinical and clinical progress will be presented. Currently we are transitioning to an iPSC derived product (CNS20-iNPC-GDNF) to replace the fetal product which is in early pre-clinical studies and seems to perform as well as it's fetal counterpart. Early data from these studies will also be presented.

Professor Clare Parish is Deputy Director and Head of the Stem Cells and Neural Development Laboratory at the Florey Institute of Neuroscience, Melbourne. Her research focuses on the use of human pluripotent stem cells to model development and disease as well as evolve strategies to improve neural transplants outcomes for the treatment of Parkinson's disease and stroke. Relevant to this presentation, in recent years she has highlighted the importance of synaptic target acquisition on graft outcomes, shown the benefit of combined cell and gene therapy to treat PD and the ability to selectively drive dopamine plasticity, as well as demonstrated the impact of exercise in enhancing the functional integration of neural grafts.

The ability of dopamine neurons within human pluripotent stem cell (hPSC)-derived neural transplants to structurally and functionally integrate in the brain in preclinical Parkinson's disease (PD) models has provided the necessary evidence for current clinical trials. Yet as with all new therapies there is a need for ongoing refinement. In recognition of the modest survival, low proportion of dopamine neurons and the inferior plasticity of these neurons compared to their fetal tissue counterparts, our team has been focused on advancing next-generation combined therapies to improve cell therapies for PD.

I will present on our recent efforts to improve the plasticity of neural grafts through environmental approaches (exercise) and dopamine targeted gene therapy

Jeffrey Kordower is the founding director of the ASU-Banner Neurodegenerative Disease Research Center and endowed chair as The Charlene and J. Orin Edson Distinguished Director at the Biodesign Institute at ASU. He has been a pioneer in the field of neural transplantation techniques and his pathbreaking investigations into the underpinnings of neurodegenerative disease have made him a leader in the field. Kordower’s interests include the study of gene and stem cell therapies, disease pathogenesis including the morphological and molecular changes during the course of neurodegeneration, learning and memory, and aging. He has published over 400 papers and chapters, has an H-index of 110 with 7 papers cites over 1,000 times, 24 citation classics (cited over 400 times), and over 50,000 total citations.

For decades, Parkinson's patients have received implants of dopaminergic cells. The most successful grafts have been implants of fetal dopaminergic progenitor cells. My lab has evaluated brains from these trials from patients who have died 18 months (n=2), 4 years (n=2), 10 years (n=1), 12 years (n=1), 16 years (n=1) and 24 years (n=1) post transplantation. For each case, robust survival of grafted cells with extensive dopaminergic innervation was observe.  Additionally, all cases older than 10 years post-transplantation displayed Lewy pathology with increasing pathology as the cases go longer. In present times, we are grafting preclinically dopaminergic progenitors from induced pluripotent stem cells. This talk will discuss the potential for these cells to have similar neuroanatomical features as seen previously in fetal dopaminergic progenitors.

I am interested in neuroscience and cancer biology to uncover the mechanisms that interconnect with CNS diseases and cancer. Our research focuses on how distinct glial cells such as myelinating oligodendrocytes and their progenitors contribute to neurological diseases, and how dysregulated developmental programs and microenvironment cross-communications contribute to tumorigenesis, recurrence and metastasis. During the postdoctoral work in Dr. Charles Stiles' lab at the Harvard Medical School, I discovered bHLH transcription factors, Olig1 and Olig2, which are critical for oligodendrocyte lineage development and brain tumorigenesis. My independent work, starting at UT Southwestern and now at Cincinnati Children's, has used a combination of state-of-the-art molecular genetic approaches and adopted novel concepts to address the mechanisms underlying demyelinating neurological disorders, such as multiple sclerosis and autism, as well as brain tumorigenesis. Our studies have contributed to an understanding of critical genetic and epigenetic mechanisms that regulate myelin repair, brain tumorigenesis and therapeutic efficacy.

Demyelinating diseases such as multiple sclerosis are among the most common and debilitating neurological disorders in the CNS, primarily due to the failure of oligodendrocyte remyelination. Myelination is essential for proper neuronal function, involving the coordinated regulatory signaling networks during myelinogenesis. Recent advances in genomics and epigenomics have revealed key regulatory molecules essential for CNS myelin regeneration. Understanding these mechanisms offers insights into the pathogenesis of demyelinating diseases and identifies potential therapeutic targets. I will discuss the latest findings in the genetic and epigenetic regulation of CNS myelination and regeneration, emphasizing their implications for neurodevelopmental and neurodegenerative diseases.

Simon Hippenmeyer studied Molecular Biology and obtained a PhD in Neurobiology at Biozentrum, University of Basel, Switzerland. He was a postdoctoral fellow at Stanford University, USA. In 2012 he joined the Institute of Science and Technology Austria (ISTA) as Assistant Professor and became Professor in 2019. Since 2020 he serves also as the Life Sciences Research Area Chair at ISTA. He received numerous awards and grants, including ERC CoG. He also serves in a number of panels such as SfN Program Committee and as vice president of the Austrian Neuroscience Association. His research focuses on fundamental neurobiological questions related to neural stem cell biology, neural development and circuit assembly.

The faithful production of correct numbers and diversity of neurons and glia by neural stem cells is essential for neural circuit assembly. In the developing cerebral cortex, radial glia progenitors (RGPs) generate all neocortical neurons and certain glia lineages. Clonal analysis using MADM (Mosaic Analysis with Double Markers) technology revealed a quantitative framework of RGP lineage progression. Here, we use MADM-based paradigms at single RGP resolution to define the cell-autonomous functions of candidate genes orchestrating RGP lineage progression. Ultimately, our results shall translate into a deeper understanding of brain function and pathological neurodevelopmental and psychiatric disorders.

Dr. Julia TCW is an Assistant Professor at Boston University and a Director of the Laboratory of Human Induced Pluripotent Stem Cell Therapeutics. She received Ph.D. and A.M. in the Department of Molecular and Cellular Biology from Harvard University and research studies in iPSC reprogramming in the Department of Stem Cell and Regenerative Biology. She then perused her postdoctoral research in the Department of Neuroscience, Ronald M. Loeb Center for Alzheimer’s Disease at Mount Sinai, New York. Her research focuses on studying Alzheimer’s disease genetics and functional genomics especially APOE using computational approaches and human iPSC models and developing therapeutic modalities. She achieved Druckenmiller Fellowship award from New York Stem Cell Foundation, NIH-NIA K and R awards, Alzheimer's Disease Research Award from BrightFocus Foundation, selected as 2022 Toffler Scholar, and received Carol and Gene Ludwig Award for Neurodegeneration Research and Edward N. and Della L. Thome Memorial Foundation Award.

Astrocytes maintain synaptic homeostasis through phagocytosing neuronal debris and protein aggregates for active clearance. Astrocytes are the major cell type in CNS, producing Apolipoprotein E (APOE) to mediate cholesterol and phospholipid transport to other cell types. APOE ε4 (APOE4) allele as the most significant genetic risk factor in Alzheimer's disease (AD) suppresses phagocytosis of Aβ plaques in astrocytes, however, the underlying molecular mechanisms of this process in human astrocytes are unknown. In this study, we utilized human induced pluripotent stem cells (iPSC) to differentiate isogenic APOE astrocytes and interrogate APOE4 impacts on uptake and degradation of neurotoxic oligomeric Aβ (oAβ) relative to the APOE3 control both in vitro and in vivo iPSC/Chimeric AD models. Our cellular phenotyping assays displayed inefficient oAβ uptake and compromised cellular degradation by APOE4 astrocytes. Unbiased transcriptomic network analysis revealed that significant changes occurred during the degradation of oAβ suppressing energy metabolism and cellular trafficking, whereas enhancing matrisome and epigenetic program. These phagocytic and degradation deficits in astrocytes may potential contribute to increase amyloid plaque accumulation in AD brains.

Binhai Zheng, Ph.D., is currently a Professor in the Department of Neurosciences at University of California San Diego School of Medicine. His lab investigates the molecular mechanisms of endogenous neural repair after CNS injury using mouse models of spinal cord injury. His work contributed to a shift from neuron-extrinsic to neuron-intrinsic hypothesis of axon regeneration. He is a member of the scientific review board for the Craig H. Neilsen Foundation, a member of the Society for Neuroscience program committee, and a co-chair for the 2025 Gordon Research Conference on Spinal Cord Injury and Regeneration.

Tremendous progress has been made on understanding the molecular mechanisms of axon regeneration and especially the neuron intrinsic control after spinal cord injury in recent years. Using high-depth single cell RNA sequencing on regenerating vs non-regenerating neurons, we developed a regeneration classifier that can be a broadly applied to predict the regenerative potential of diverse neuronal types based on their single cell profiles. Such classifiers may serve as a new generation of biomarkers for testing molecular and cellular intervention in pre-clinical models of neurological conditions. Implications on future neural repair research will be discussed.

Alfred has a long standing interest in developing human neural cell models for basic discoveries and translational neuroscience. He has made contributions to both transcription factor-directed and morphogen guided ways of neuronal subtype differentiation, and has applied these methods to model neurological disease such as epilepsy and PD. Currently his lab is focusing on developing human midbrain organoids to better understand PD pathophysiology.

More than a dozen different protocols exist to differentiate hPSCs to midbrain dopaminergic neurons (mDANs), the major cell types that selectively degenerate in Parkinson's disease. What is the diversity of cell types generated? How faithful are they compare to the real human mDANs? Here I will present our effort to address this question using scRNA sequencing.

Dr. Xiaolong Zheng received his Ph.D in neurology from Huazhong University of Science & Technology China and currently works as a postdoctoral in Tongji Hospital in Wuhan, China. Dr. Xiaolong Zheng is committed to differentiating human pluripotent stem cells into multiple types of spinal cord neurons, and utilizing them to treat spinal cord diseases such as spinal cord injury in rodents and nonhuman primates. He has received fundings from National Natural Science Foundation of China and the China Postdoctoral Science Foundation. His work has been published in Cell Reports, Stem Cell Reports and iScience.

Loss of dorsal spinal GABA neurons after spinal cord injury (SCI) contributes to neuropathic pain. Here, human embryonic stem cells were differentiated into spinal dI4 GABA neurons. Six months after transplantation into rat injured spinal cord, they formed inhibitory synapses with rat sensory interneurons and formed presynaptic inhibition synapses with rat primary sensory afferents and were innervated by supraspinal descending pain modulation centers including the dorsal raphe and rostral ventral medulla. Mechanical allodynia and thermal hyperalgesia were significantly alleviated in grafted rats. These results suggested that transplantation of human spinal GABA neurons could treat neuropathic pain after SCI.