Twenty years ago a seminal discovery by researchers at UW-Madison introduced stem cells to the world. Since then, this new tool has transformed science and opened new avenues for translational research. Stem cells are undifferentiated “master cells” with the ability to differentiate into any of the body’s cell types. Waisman Center researchers have been at the forefront of stem cell research since its inception and have made pioneering advancements in utilizing these specialized cells to better understand brain development and in research focused on neurodegenerative diseases such as Parkinson’s, ALS, and Alzheimer’s as well as developmental disabilities such as autism, Down syndrome, and fragile X syndrome.
Listed below are milestones in stem cell research by Waisman Center investigators.
2001: The Waisman Center establishes a stem cell research program. The program is part of a $25 million expansion – adding a north tower and an additional 71,000 square feet. (Expanded Waisman Center Facilities Support Vital Programs)
2001: Waisman Center investigator Su-Chun Zhang, MD, PhD, shows that human embryonic stem cells, coaxed into becoming early-stage brain cells, can be transplanted into rodent models and grow into neurons. (Stem cells, forged into neurons, show promise for brain repair)
2005: Waisman Biomanufacturing, led by then-director Derek Hei, PhD, partners with the WiCell Research Institute and a team of UW investigators to establish the first National Stem Cell Bank. (WiCell receives $16 million NIH grant to create national stem cell bank)
2005: Su-Chun Zhang, MD, PhD, shows that human embryonic stem cells can be coaxed into becoming spinal motor neurons that relay messages from the brain to the body, and midbrain dopamine neurons that coordinate movement. (Waisman researchers grow critical nerve cells)
2007: Waisman Center investigator David Gamm, MD, PhD, shows that neural progenitor cells protect and sustain retinal cells in rodent models with degenerative eye diseases akin to those that afflict humans. (Stem cell therapy research by David Gamm shows promise for rescuing deteriorating vision)
2009: David Gamm, MD, PhD, successfully grows multiple types of retina cells from two types of stem cells, opening the door to laboratory models for studying genetically linked eye conditions, screening new drugs to treat those conditions, and understanding the development of the eye. (Wisconsin team grows retina cells from skin-derived stem cells)
2009: The Waisman Center establishes an induced pluripotent stem cell (iPSC) core to streamline the production of iPSCs allowing investigators to focus their time and resources on the application and use of the cells in their research. (First cGMP Feeder-Independent Pluripotent Stem Cell Banks Released for Distribution)
2011: Xinyu Zhao, PhD, discovers a connection between neurogenesis –the process of generating neurons – and learning deficits in animal models of fragile X syndrome. Her findings suggest that promoting neurogenesis using stem cells may have therapeutic potential for people with fragile X syndrome and other neurological disorders. (Neurogenesis and Learning: Making Connections in Fragile X Syndrome)
2011: David Gamm, MD, PhD, generates three-dimensional structures that are similar to those present at the earliest stages of retinal development, making them potentially valuable not only for studying how the human retina develops, but also how to keep it working in the face of disease. (Stem Cells From Patients Make Early Retina in a Dish)
2011: Su-Chun Zhang, MD, PhD, discovers that neurons, forged in a lab from human embryonic stem cells and implanted into the brains of mice, can successfully fuse with the brains’ wiring and both send and receive signals. (Stem cells, forged into neurons, show promise for brain repair)
2011: A group of scientists led by Su-Chun Zhang, MD, PhD, directs embryonic and human induced stem cells to become astrocytes in a lab dish, giving researchers a powerful new tool to devise new therapies and drugs for neurological disorders. (Human brain’s most ubiquitous cell cultivated in lab dish)
2012: David Gamm, MD, PhD, and several Waisman Center scientists create a laboratory model for macular degeneration using induced pluripotent stem cells. (Cells from skin create model of blinding eye disease)
2013: Su-Chun Zhang, MD, PhD, transforms stem cells into nerve cells that helped animal models regain the ability to learn and remember. This novel study is the first to show that human stem cells can successfully implant themselves in the brain and then ameliorate neurological deficits. (Stem cell transplant restores memory, learning in mice)
2013: Using cells derived from skin samples of individuals with Down syndrome (DS), Anita Bhattacharyya, PhD, cultivates a line of DS brain cells. These cells provide insight about early brain development in individuals with DS and will potentially be used to test or design drugs to target symptoms of DS. (Waisman scientists model human disease in stem cells)
2014: Su-Chun Zhang, MD, PhD, pinpoints an error in protein formation that could be the root of amyotrophic lateral sclerosis (ALS). (Study helps unravel the tangled origin of ALS)
2015: Su-Chun Zhang, MD, PhD, develops a new technique to “edit” or silence genes in human stem cells at any stage of development. This discovery has the potential to revolutionize biomedical research and provide unprecedented understanding of how stem cells function. (Expert: Editing stem cell genes will “revolutionize” biomedical research)
2016: Su-Chun Zhang, MD, PhD, using a new gene editing technique, inserts a genetic switch that alters the production of dopamine in nerve cells through specialized drug therapy. (Cell transplant treats Parkinson’s in mice under control of designer drug)
2016: Anita Bhattacharyya, PhD, and Xinyu Zhao, PhD, use CRISPR-Cas9 to position a reporter cell line in the genomes of stem cells derived from individuals with FXS that gives off a luminescence signal if the FMRI gene is turned off. (Waisman researchers win an inaugural UW2020 award)
2017: Xinyu Zhao, PhD, conducts one of the first studies to show that the MBD1 gene plays a pivotal role in maintaining the ‘stemness’ of neural cells. (Am I a stem cell? How do I know?)
2018: Qiang Chang, PhD, uncovers how the loss of MECP2 function can affect calcium dynamics in astrocytes and the potential link between defects within astrocytes that have lost MECP2 function with more widespread problems in the brains of individuals with Rett syndrome. (Waisman research into rare syndrome offers hope for families)
2018: Su-Chun Zhang, MD, PhD, and Albee Messing, VMD, PhD, show that GFAP buildup in astrocytes, using iPSCs donated by two Alexander disease patients, disrupts organelles and cellular communication via calcium waves, expanding our understanding of the fundamental biology of the commonly studied cells. (Mutation in common protein triggers tangles, chaos inside brain cells)