About iPS Cells
What are IPS cells?
Induced pluripotent stem (iPS) cells are blood or skin cells that are genetically reprogrammed to a pluripotent state. This mean that once reprogrammed, iPS cells have the remarkable potential to be turned into any type of cell in the body, including brain and nerve cells. They can be kept alive in the lab and stored indefinitely.
Why are IPS cells important?
Researchers use iPS cells to study the specific causes and consequences of developmental disabilities and neurodegenerative diseases. iPS cells derived from skin or blood samples donated by individuals with these conditions are particularly revealing to researchers studying the progression of brain development within a specific condition. iPS cells are an important tool to screen therapeutics that may be effective in treating developmental disabilities and neurodegenerative diseases.
Conditions Studied at Waisman
The following conditions are under study by Waisman Center investigators using iPS cells.
- Alexander disease (Albee Messing, VMD, PhD, Su-Chun Zhang, MD, PhD)
- Amyotrophic lateral sclerosis (ALS) (Masatoshi Suzuki, DVM, PhD, Su-Chun Zhang, MD, PhD)
- Autism (Xinyu Zhao, PhD)
- Best’s disease (David Gamm, MD, PhD)
- Charcot Marie Tooth (John Svaren, PhD)
- Down syndrome (Anita Bhattacharyya, PhD)
- Fragile X syndrome (Anita Bhattacharyya, PhD, Xinyu Zhao, PhD)
- Pelizaeus-Merzbacher Disease
- Retinitis Pigmentosa (David Gamm, MD, PhD)
- Rett syndrome (Qiang Chang, PhD, Xinyu Zhao, PhD)
- Spinal cord injury (Su-Chun Zhang, MD, PhD)
- Spinal muscular atrophy (Masatoshi Suzuki, DVM, PhD, Su-Chun Zhang, MD, PhD)
- Usher Syndrome (David Gamm, MD, PhD)
Reprogrammed skin cells develop into neural (nervous system) cells that can produce brain and spinal cord tissue. Zhang Lab
Fluorescence microscopy image of a nerve cell derived from induced pluripotent stem cells donated by an individual with Rett syndrome. Chang Lab.
The figure shows neural stem cells (green) in adult mouse hippocampus; these are the cells affected by the lack of FMRP in fragile X syndrome. By targeting these cells, researchers were able to restore cognitive functions in fragile X mice. Zhao Lab
Stem cells in the earliest stages of retinal development - used for studying how the human retina develops, and how to keep it working in the face of disease. Gamm Lab
iPS cell research is a relatively new field in the world of science. In 2008, Japanese scientist Shinya Yamanaka and James Thomson at the University of Wisconsin–Madison managed to reprogram adult cells from humans into iPS cells. By 2009, Waisman Center researchers began collecting skin samples from individuals with developmental disabilities for iPS cell research. Prior to the discovery of iPS cells, it was customary for stem cell research to be done using embryos obtained from humans. Below is a highlight of stem cell and iPS cell research milestones made by researchers at the Waisman Center and other departments on the University of Wisconsin-Madison campus
1998: Human stem cell research starts at UW. UW-Madison Professor James Thomson VMD, PhD, derives the first embryonic stem cell lines from human embryos. These cells can give rise to every cell type in the body providing researchers a renewable source for studying human development, disease, and therapies. (Learn more: Wisconsin scientists culture elusive embryonic stem cells)
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 rodents and grown into neurons. (Learn more: Stem cells, forged into neurons, show promise for brain repair)
2005: Waisman Biomanufacturing partners with the WiCell Research Institute and a team of UW-Madison investigators to establish the first National Stem Cell Bank. The stem cell bank houses many different types of stem cells from around the globe to support stem cell research. (Learn more: WiCell receives $16 million NIH grant to create national stem cell bank)
2008: Shinya Yamanaka and UW Professor James Thomson produce the first induced pluripotent stem cells (iPS cells). iPS cells are created by reprogramming adult skin or blood cells back into an embryonic-like state and can be grown into every cell type of the body. This technology has provided a powerful tool for studying human disease. (Learn more: James Thomson receives 2008 Massry Prize honoring stem cell researchers)
2009: The Waisman Center establishes an iPS cells core to streamline the production of iPS cells, thereby allowing investigators to focus their time and resources on the application of stem cells to biomedical research and therapy development. (Learn more: First cGMP Feeder-Independent Pluripotent Stem Cell Banks Released for Distribution)
2010: Waisman Center investigator David Gamm MD, PhD, generates iPS cells from skin samples obtained from individuals with Best disease, an inherited degenerative disease of the macula that causes progressive and irreversible vision loss. The iPS cells were then used to study the cellular mechanisms responsible for Best disease. (Learn more: Wisconsin team grows retina cells from skin-derived stem cells)
2010: Waisman Center investigator Qiang Chang PhD, generates iPS cells from skin samples obtained from individuals with Rett Syndrome. The Chang lab differentiated the iPS cells into brain cells to study the characteristics and mechanisms of the neurodevelopmental disorder Rett Syndrome.
2010: Waisman Center researchers create iPS cell-derived brain cells from skin samples obtained from individuals with fragile X syndrome (FXS) to examine neuronal deficits. The investigators discovered that FXS neurons developed abnormally and had deficits in neurite initiation and extension.
2011: Using iPS cells generated from patients with Lou Gehrig’s disease (ALS), Waisman Center researchers discover that misregulation of a protein found in brain cells is a critical early step that leads to the pathology seen in ALS motoneurons. This research highlights the possibility of targeting neurofilament regulation for therapeutic intervention.
2012: David Gamm, MD, PhD, and several Waisman Center scientists create a laboratory model for macular degeneration using iPS cells. The laboratory model utilizes retinal tissue composed of authentic human photoreceptor cells that behave like those found in the eye and is valuable for studying how the human retain develops. (Learn more: Scientists Produce Eye Structures from Human Blood-Derived Stem Cells & A Promising Sight)
2013: Using iPS cells from skin samples of individuals with Down syndrome (DS), Waisman Center investigator Anita Bhattacharyya, PhD, cultivates a line of DS brain cells. These cells provide insight about early brain development in individuals with DS and will be used to design and test drugs to target symptoms of DS. (Learn more: Down syndrome neurons grown from stem cells show signature problems)
2015: Skin samples are obtained from individuals with Pelizaeus-Merzbacher disease for creation of iPS cells. Pelizaeus-Merzbacher is characterized by hypomyelination, meaning that the nervous system has a reduced ability to form myelin leading to a reduction in brain function. The iPS cells are being used by Waisman Center investigators to research the cellular mechanisms causing Pelizaeus-Merzbacher disease and provide insights into future therapies.
2015: Waisman Stem Cell Core receives campus funding from UW2020 program to establish the Waisman Gene Editing Core to provide gene editing services for stem cell researchers. (Learn more: Waisman researchers win an inaugural UW2020 award)
2016: Waisman Center’s Anita Bhattacharyya, PhD, and Xinyu Zhao, PhD, use FXS iPS cells to create a FXS-reporter cell line as a tool to discover and test potential chemical therapies that can reactivate the FMR1 gene which is “turned off” in FXS. (Learn more: Lighting up the search for a therapy for fragile X syndrome)
2017: Skin samples are obtained from individuals with a rare genetic form of autism for the creation and study of iPS cells at the Waisman Center.
2018: Su-Chun Zhang, MD, PhD, and Albee Messing, VMD, PhD, utilize iPS cells donated by individuals with Alexander disease to study how the disease causes buildup of a protein called GFAP in brain cells. They discover that the buildup of protein disrupts the cellular communication and normal cellular functions, expanding the mechanistic understanding of Alexander disease. (Learn more: Mutation in common protein triggers tangles, chaos inside brain cells)
2021: Anita Bhattacharyya, PhD, Su-Chun Zhang, MD, PhD, together with Daifeng Wang, PhD and André Sousa, PhD, are leading a new effort to develop a model for brain development in Down syndrome that relies on stem cells funded by an $11 million grant from the NIH. (Learn more: Stem cell project to create new model to study brain development and Down syndrome)