iPSC – Induced Pluripotent Stem Cells

Induced pluripotent stem (iPS) cells are blood or skin cells that are genetically reprogrammed to a pluripotent state. Once reprogrammed, iPS cells can be turned into any type of cell in the body.

iPS cells are made from skin cells obtained from a patient skin biopsy or from a blood sample. During the biopsy, a tiny skin sample—the size of a pencil eraser tip—is taken from the upper arm of the donor. Once the sample is obtained, the tissue is transferred to the Waisman Center’s iPS Cell Core where the cells are reprogrammed to a pluripotent state. The iPS Cell Core expands the cell lines and then transfers the iPS cells to scientists for research. The reprogramming process takes two to three months to complete.

The Waisman Center iPS Cell Core is working to derive iPS cell lines for the benefit of stem cell researchers at UW-Madison and beyond. Directed by Su-Chun Zhang, MD, PhD, the iPS Cell Core streamlines the very specific and technical process of producing iPS cells, allowing scientists to focus their time and resources on the actual application and use of iPS cells in their research. This work is in collaboration with the WiCell Research Institute.

Waisman Center scientists use iPS cells to investigate the specific causes and consequences of developmental disabilities and neurodegenerative diseases. iPS cells derived from skin or blood samples donated by individuals with developmental or neurodegenerative disorders are particularly revealing to researchers studying the progression of brain development within a specific conditions. iPS cells are an important tool to screen therapeutics that may be effective in treating developmental disabilities and neurodegenerative diseases.

iPS Cell Types Utilized by Waisman Center Investigators

• Alexander disease (Albee Messing, VMD, PhD, Su-Chun Zhang, MD, PhD)
• Amyotrophic lateral sclerosis (ALS) (Masatoshi Suzuki, DVM, PhD, Su-Chun Zhang, MD, 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)
• Hearing loss (Su-Chun Zhang, MD, PhD)
• Retinitis Pigmentosa (David Gamm, MD, PhD)
• Rett syndrome (Qiang Chang, PhD, Xinyu Zhao, PhD)
• Stroke (Darcie L. Moore, 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)

iPS cells are used to investigate the causes and consequences of these conditions studied at the Waisman Center:

• Neurons (different subtypes)
• Astrocytes
• Oligodendrocytes
• Schwann cells

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. (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. (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. (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 (iPSCs). iPSCs 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. (James Thomson receives 2008 Massry Prize honoring stem cell researchers)

2009: The Waisman Center establishes an iPSC core to streamline the production of iPSCs, thereby allowing investigators to focus their time and resources on the application of stem cells to biomedical research and therapy development. (First cGMP Feeder-Independent Pluripotent Stem Cell Banks Released for Distribution)

2010: Waisman Center investigator David Gamm MD, PhD, generates iPSCs from skin samples obtained from individuals with Best disease, an inherited degenerative disease of the macula that causes progressive and irreversible vision loss. The iPSCs were then used to study the cellular mechanisms responsible for Best disease. (Wisconsin team grows retina cells from skin-derived stem cells)

2010: Waisman Center investigator Qiang Chang PhD, generates iPSCs from skin samples obtained from individuals with Rett Syndrome. The Chang lab differentiated the iPSCs into brain cells to study the characteristics and mechanisms of the neurodevelopmental disorder Rett Syndrome.

2010: Waisman Center researchers create iPSC-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 iPSCs 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 iPSCs. 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. (Scientists Produce Eye Structures from Human Blood-Derived Stem Cells)

2013: Using iPSCs 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. (Down syndrome neurons grown from stem cells show signature problems)

2015: Skin samples are obtained from individuals with Pelizaeus-Merzbacher disease for creation of iPSCs. 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 iPSCs 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. (Waisman researchers win an inaugural UW2020 award)

2016: Waisman Center’s Anita Bhattacharyya, PhD, and Xinyu Zhao, PhD, use FXS iPSCs 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. (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 iPSCs at the Waisman Center.

2018: Su-Chun Zhang, MD, PhD, and Albee Messing, VMD, PhD, utilize iPSCs 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. (Mutation in common protein triggers tangles, chaos inside brain cells)