BUFFALO, N.Y. A new study led by a researcher in the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo has important implications for developing future treatments for Parkinsons disease (PD), a progressive nervous system disorder that affects movement and often includes tremors.
In this study, we find a method to differentiate human induced pluripotent stem cells (iPSCs) to A9 dopamine neurons (A9 DA), which are lost in Parkinsons disease, says Jian Feng, PhD, professor of physiology and biophysics in the Jacobs School and the senior author on the paper published May 24 in Molecular Psychiatry.
These neurons are pacemakers that continuously fire action potentials regardless of excitatory inputs from other neurons, he adds. Their pacemaking property is very important to their function and underlies their vulnerability in Parkinsons disease.
This exciting breakthrough is a critical step forward in efforts to better understand Parkinsons disease and how to treat it, says Allison Brashear, MD, UBs vice president for health sciences and dean of the Jacobs School. Jian Feng and his team are to be commended for their innovation and resolve.
Feng explains there are many different types of dopamine neurons in the human brain, and each type is responsible for different brain functions.
Nigral dopamine neurons, also known as the A9 DA neurons, are responsible for controlling voluntary movements. The loss of these neurons causes the movement symptoms of Parkinsons disease, he says.
Scientists have been trying hard to generate these neurons from human pluripotent stem cells to study Parkinsons disease and develop better therapies, Feng says. We have succeeded in making A9 dopamine neurons from human induced pluripotent stem cells. It means that we can now generate these neurons from any PD patients to study their disease.
Feng notes that A9 DA neurons are probably the largest cells in the human body. Their volume is about four times the volume of a mature human egg.
Over 99 percent of the volume is contributed by their extremely extensive axon branches. The total length of axon branches of a single A9 DA neuron is about 4.5 meters, he says. The cell is like the water supply system in a city, with a relatively small plant and hundreds of miles of water pipes going to each building.
In addition to their unique morphology, the A9 DA neurons are pacemakers they fire action potentials continuously regardless of synaptic input.
They depend on Ca2+ channels to maintain the pacemaking activities. Thus, the cells need to deal with a lot of stress from handling Ca2+ and dopamine, Feng says. These unique features of A9 DA neurons make them vulnerable. Lots of efforts are being directed at understanding these vulnerabilities, with the hope of finding a way to arrest or prevent their loss in Parkinsons disease.
Pacemaking is an important feature and vulnerability of A9 DA neurons. Now that we can generate A9 DA pacemakers from any patient, it is possible to use these neurons to screen for compounds that may protect their loss in PD, Feng notes. It is also possible to test whether these cells are a better candidate for transplantation therapy of PD.
To differentiate human iPSCs to A9 DA neurons, the researchers tried to mimic what happens in embryonic development, in which the cells secrete proteins called morphogens to signal to each other their correct position and destiny in the embryo.
Feng notes the A9 DA neurons are in the ventral part of the midbrain in development.
Thus, we differentiate the human iPSCs in three stages, each with different chemicals to mimic the developmental process, he says. The challenge is to identify the correct concentration, duration, and treatment window of each chemical.
The combination of this painstaking work, which is based on previous work by many others in the field, makes it possible for us to generate A9 DA neurons, Feng adds.
Feng points out there are a number of roadblocks to studying Parkinsons disease, but that significant progress is being made.
There is no objective diagnostic test of Parkinsons disease, and when PD is diagnosed by clinical symptoms, it is already too late. The loss of nigral DA neurons has already been going on for at least a decade, he says.
There was previously no way to make human dopamine neurons from a PD patient so we could study these neurons to find out what goes wrong.
Scientists have been using animal models and human cell lines to study Parkinsons disease, but these systems are inadequate in their ability to reflect the situation in human nigral DA neurons, Feng says.
Just within the past 15 years, PD research has been transformed by the ability to make patient-specific dopamine neurons that are increasingly similar to their counterparts in the brain of a PD patient.
Houbo Jiang, PhD, research scientist in the Department of Physiology and Biophysics, and Hong Li, PhD, a former postdoctoral associate in the Department of Physiology and Biophysics, are co first-authors on the paper.
Other co-authors on the study are: Hanqin Li, PhD, a graduate of the doctoral program in neuroscience and currently a postdoctoral fellow at University of California, Berkeley; Li Li, a trainee in UBs doctoral program in neuroscience; and Zhen Yan, PhD, SUNY Distinguished Professor of physiology and biophysics.
The study was funded by the Department of Veterans Affairs, National Institutes of Health and by New York State Stem Cell Science (NYSTEM).
Read more from the original source:
UB-led study presents critical step forward in understanding Parkinson's disease and how to treat it - University at Buffalo
- Stem Cell Therapy for Treatment of Ocular Disorders - Hindawi - December 27th, 2022
- Researchers find out why some stress is good for you - November 6th, 2022
- Shinya Yamanaka - Wikipedia - October 29th, 2022
- Implanting a Patient's Own Reprogrammed Stem Cells Shows Early Positive ... - October 29th, 2022
- World's first stem cell treatment for spina bifida delivered during fetal surgery - UC Davis Health - October 13th, 2022
- JDRF Announces the Appointment of Qizhi Tang, Ph.D., as Co-Director of The JDRF Center of Excellence in Northern California - PR Newswire - October 13th, 2022
- California court creates regulatory uncertainty over the FDA regulation of stem cell therapies - BioEdge - October 4th, 2022
- Scientists have created a mechanical womb that can grow life in the lab - Inverse - October 4th, 2022
- ISCT: California stem cell ruling is flawed and has inserted regulatory uncertainty into the CGT market - BioPharma-Reporter.com - September 16th, 2022
- Scientists Use Stem Cells to Create Synthetic Mouse Embryos - September 16th, 2022
- UK Equine Research Hall of Fame Inductees Announced - Equi Management - September 16th, 2022
- Cultured meat startup Prolific Machines unveils its Henry Ford approach to cell growth - TechCrunch - September 16th, 2022
- New Stem Cell Therapy Protects Brain Against the Neurological Disorder - Nature World News - September 8th, 2022
- Scientists Are Working on New and Improved Hair Loss Treatments - Gizmodo - September 8th, 2022
- What happens to the brain on prescription steroids? - Medical News Today - September 8th, 2022
- How this scientist uses Legos to explain the power of stem cells - August 30th, 2022
- CIRM Bridges intern researches stem cells to grow kidneys - August 30th, 2022
- Alzheimer's: Could controlling the brain's own clean-up crew help? - Medical News Today - August 22nd, 2022
- Trial to Compare Safety and Efficacy of Novel Cell Therapy to Standard of Care in Patients With Rare Blood Cancers - Curetoday.com - August 5th, 2022
- Medpoint Global was awarded the Best Revolutionary Hair Transplant Center of the Year and continues to follow developments in its field and offer more... - August 5th, 2022
- Cell Culture Media Market Worth $14.64 Billion by 2029 - Exclusive Report by Meticulous Research - GlobeNewswire - August 5th, 2022
- Haifan Lin takes on new role as President of the ISSCR - EurekAlert - July 3rd, 2022
- UCI-led team discovers signaling molecule that potently stimulates hair growth - UCI News - July 3rd, 2022
- Calidi Biotherapeutics Announces Appointment of W.K. Alfred Yung, M.D., to its Medical Advisory Board - Business Wire - July 3rd, 2022
- Organoids reveal similarities between myotonic dystrophy type 1 and Rett syndrome - EurekAlert - July 3rd, 2022
- Our View: Roe reversal hard hit to science - The Durango Herald - July 3rd, 2022
- Connection Map Reveals Changes in the Injured Brain - Technology Networks - June 22nd, 2022
- Scientists Used CRISPR to Trace Every Human Gene to Its Function - Singularity Hub - June 22nd, 2022
- Maike Sander named to lead the Max Delbrck Center - EurekAlert - June 22nd, 2022
- CRISPR-Cas12a Editing Rates Improve with Better Directions to the Nucleus - Genetic Engineering & Biotechnology News - June 22nd, 2022
- Stem Cells: A Case for the Use of Human Embryos in Scientific Research - June 4th, 2022
- Top Beverly Hills Plastic Surgeon, Dr. John Anastasatos, Explores Cell-Assisted Lipotransfer (CAL) with Breast Augmentation in New Publication -... - June 4th, 2022
- Regenerative Medicine Market To Grow At A CAGR Of 11.27% By 2027, Due To Advancements In Cell Biology, Genomics Research, And Gene-Editing Technology... - June 4th, 2022
- Google Reverses Ban on Ads for All Stem Cell Therapies, Will Allow FDA-Approved Ones - Gizmodo Australia - May 15th, 2022
- Head-To-Head Survey: Jasper Therapeutics (NASDAQ:JSPR) & CytRx (OTCMKTS:CYTR) - Defense World - May 15th, 2022
- Primary Cell Culture Market Mechanical Separation Segment Is Expected To Witness A Lucrative CAGR Of 11.7% Till 2028, Owing To Advancements In... - May 15th, 2022
- Ray Therapeutics Receives $4M in Funding From the California Institute for Regenerative Medicine (CIRM) - BioSpace - May 2nd, 2022
- Predicting the Future of Food - Bon Appetit - May 2nd, 2022
- FDA Grants Direct Biologics Regenerative Medicine Advanced Therapy (RMAT) Designation for the use of ExoFlo in COVID-19 Related ARDS USA - English -... - April 19th, 2022
- Chronic Diseases Is Expected To Have Positive Impact On Stem Cell Characterization Kits Market Demand Bloomingprairieonline - Bloomingprairieonline - April 19th, 2022
- Cleveland Cord Blood Center and Deverra Therapeutics Announce Agreement - Yahoo Finance - April 6th, 2022
- A model that mimics malformation associated with severe epilepsy paves way to novel therapies - EurekAlert - March 25th, 2022
- Stem cell agency: Following the money - and its performance - Capitol Weekly - December 24th, 2021
- Epithelial Cell Culture Media Market to hit US$ 303040.33 thousand by 2028, at 11.4% CAGR: The Insight Partners - Digital Journal - December 24th, 2021
- What is Biohacking? Understanding the Silicon Valley Wellness Trend Youll Hear About in 2022 - SheKnows - December 24th, 2021
- Second Woman Spontaneously Clears HIV: 'We Think More Are Out - Medscape - November 22nd, 2021
- Business Partnership for Development and Commercialization of Medical Device Implant Utilizing MSC2 for the Regeneration of Esophageal Tissue in... - November 22nd, 2021
- Misinformation on stem cell treatments for COVID-19 linked to overhyped science, researchers argue - EurekAlert - October 16th, 2021
- Phase 2 Clinical Trial Data of NurOwn in Progressive MS Will Be Presented at the 37th Congress of the European Committee for Treatment and Research in... - October 16th, 2021
- StemExpress Partners with the Alliance for Regenerative Medicine to Provide COVID-19 Testing for the Cell and Gene Meeting on the Mesa - WSAW - October 5th, 2021
- BrainStorm to Present at the 2021 Cell & Gene Meeting on the Mesa - WWNY - October 5th, 2021
- UC Davis and the School of Medicine set new records in research funding - UC Davis Health - August 31st, 2021
- FDA gives speedy review to Bayer's Parkinson's stem cell therapy - - pharmaphorum - July 21st, 2021
- Stem cell model reveals how COVID-19 can infect the brain - Study Finds - July 21st, 2021
- Introducing the 3D bioprinted neural tissues with the potential to 'cure' human paralysis - 3D Printing Industry - July 21st, 2021
- Insception Lifebank and Cells for Life Join the Generate Life Sciences Family to Create a Global Platform - Canada NewsWire - June 6th, 2021
- Innovative Regenerative Medicine Therapies Safety Comes First - FDA.gov - June 6th, 2021
- ViaCyte to Present Late-Breaking Data at the American Diabetes Association's 81st Scientific Sessions - PRNewswire - June 6th, 2021
- Viral vector unlikely to be cause of leukemia in gene therapy patient - Science Magazine - March 11th, 2021
- Astrocytes Derived from Patients with Bipolar Disorder Malfunction - UC San Diego Health - March 11th, 2021
- Peer Recognition | The UCSB Current - The UCSB Current - March 11th, 2021
- Stem cells on the ballot - Science Magazine - January 20th, 2021
- Controlling the immune system with 'invisible stem' cells - BioNews - January 20th, 2021
- How a UCSF team is giving Cronutt the sea lion a second chance with neuroscience - University of California - October 20th, 2020
- What Proposition 14 Tells Us About California - The New York Times - October 20th, 2020
- California Proposition 14: Funding medical research that uses stem cells - KTLA - October 20th, 2020
- Technology to natures rescue - The Hindu - October 20th, 2020
- What You Need to Know About Prop 14, The Stem Cell Research Bond (Transcript) - KQED - October 5th, 2020
- UC Davis Engineers Lead $36M Effort to Improve Recovery From Spinal Cord Injuries - UC Davis - October 5th, 2020
- Dust off the crystal ball: It's time for STAT's 2020 Nobel Prize predictions - STAT - October 5th, 2020
- Stem Cells Offer Hope of Treatment for COVID-19 Patients with Acute Respiratory Distress Syndrome (ARDS) - HospiMedica - September 15th, 2020
- David Shavelle, MD, Named Medical Director of Adult Cardiology for the MemorialCare Heart & Vascular Institute at Long Beach Medical Center -... - September 15th, 2020
- Seeing the eye like never before | Newsroom - UW Medicine Newsroom - September 15th, 2020
- Why The FDA's Recent Approval Of New Vaccine Is A Gigantic Win In The War On Cancer - Innovation & Tech Today - September 7th, 2020
- Gore partners with San Diego company on cell delivery system with potential to treat Type 1 diabetes - delawarebusinessnow.com - August 12th, 2020
- Celularity announces the activation of first California Clinical Trial Site following CIRM Grant Award to Advance Treatments for COVID-19 - PRNewswire - August 12th, 2020
- Meet The 12 Next-Gen Food Techs Transforming The Future Of Protein - Green Queen Media - August 12th, 2020
- BeyondSpring Initiates Expanded Access Program with Plinabulin for Patients Suffering from CIN in the US - BioSpace - August 12th, 2020
- BCLI: Phase 3 ALS Data Expected by the End of November 2020 - Yahoo Finance - August 12th, 2020
- Impact of COVID 19 pandemic on Stem Cell Characterization and Analysis Tools Market Structure and Its Segmentation - 3rd Watch News - July 1st, 2020