Reprogramming stem cells may prevent cancer after radiation
Posted: December 30, 2014 at 3:44 am
The body has evolved ways to get rid of faulty stem cells. A University of Colorado Cancer Center study published in the journal Stem Cells shows that one of these ways is a "program" that makes stem cells damaged by radiation differentiate into other cells that can no longer survive forever. Radiation makes a stem cell lose its "stemness." That makes sense: you don't want damaged stem cells sticking around to crank out damaged cells.
The study also shows that this same safeguard of "programmed mediocrity" that weeds out stem cells damaged by radiation allows blood cancers to grow in cases when the full body is irradiated. And by reprogramming this safeguard, we may be able to prevent cancer in the aftermath of full body radiation.
"The body didn't evolve to deal with leaking nuclear reactors and CT scans. It evolved to deal with only a few cells at a time receiving dangerous doses of radiation or other insults to their DNA," says James DeGregori, PhD, investigator at the CU Cancer Center, professor of Biochemistry and Molecular Genetics at the CU School of Medicine, and the paper's senior author.
DeGregori, doctoral student Courtney Fleenor, and colleagues explored the effects of full body radiation on the blood stem cells of mice. In this case, radiation increased the probability that cells in the hematopoietic stem cell system would differentiate. Only, while most followed this instruction, a few did not. Stem cells with a very specific mutation were able to disobey the instruction to differentiate and retain their "stemness." Genetic inhibition of the gene C/EBPA allowed a few stem cells to keep the ability to act as stem cells. With competition from other, healthy stem cells removed, the stem cells with reduced C/EBPA were able to dominate the blood cell production system. In this way, the blood system transitioned from C/EBPA+ cells to primarily C/EBPA- cells.
Mutations and other genetic alterations resulting in inhibition of the C/EBPA gene are associated with acute myeloid leukemia in humans. Thus, it's not mutations caused by radiation but a blood system reengineered by faulty stem cells that creates cancer risk in people who have experienced radiation.
"It's about evolution driven by natural selection," DeGregori says. "In a healthy blood system, healthy stem cells out-compete stem cells that happen to have the C/EBPA mutation. But when radiation reduces the heath and robustness (what we call 'fitness') of the stem cell population, the mutated cells that have been there all along are suddenly given the opportunity to take over."
Think about it in terms of chipmunks and squirrels: reducing an ecosystem's population of chipmunks may allow squirrels to flourish -- especially if the way in which chipmunks are reduced changes the ecosystem to favor squirrels, similar to how radiation changes the body in a way that favors C/EBPA-mutant stem cells).
These studies don't just tell us why radiation makes hematopoietic stem cells (HSCs) differentiate; they also show that by activating a stem cell maintenance pathway, we can keep it from happening. Even months after irradiation, artificially activating the NOTCH signaling pathway of irradiated HSCs lets them act "stemmy" again -- restarting the blood cell assembly line in these HSCs that would have otherwise differentiated in response to radiation.
When DeGregori, Fleenor and colleagues activated NOTCH in previously irradiated HSCs, it kept the population of dangerous, C/EBPA cells at bay. Competition from non-C/EBPA-mutant stem cells, with their fitness restored by NOTCH activation, meant that there was no evolutionary space for C/EBPA-mutant stem cells.
"If I were working in a situation in which I was likely to experience full-body radiation, I would freeze a bunch of my HSCs," DeGregori says, explaining that an infusion of healthy HSCs after radiation exposure would likely allow the healthy blood system to out-compete the radiation-exposed HSC with their "programmed mediocrity" (increased differentiation) and even HSC with cancer-causing mutations. "But there's also hope that in the future, we could offer drugs that would restore the fitness of stem cells left over after radiation."
More:
Reprogramming stem cells may prevent cancer after radiation
- Eli and Edythe Broad Center of Regeneration Medicine and ... - October 30th, 2015
- Molecular & Cellular Medicine - October 29th, 2015
- Sickle cell anemia Treatments and drugs - Mayo Clinic - October 29th, 2015
- How are stem cells used in medicine today? - HowStuffWorks - October 29th, 2015
- Oxidative Medicine and Cellular Longevity An Open Access ... - October 29th, 2015
- Department of Regenerative Medicine and Cell Biology - October 29th, 2015
- Sickle Cell Anemia: MedlinePlus - National Library of Medicine - October 29th, 2015
- Personalized RegenerativeMedicine : Dr David Steenblock - October 29th, 2015
- Cell Therapy and Regenerative Medicine - October 29th, 2015
- The Power of Stem Cells | California's Stem Cell Agency - October 29th, 2015
- Herbal medicine | Cancer Research UK - October 29th, 2015
- UR Stem Cell and Regenerative Medicine Institute (SCRMI) - October 29th, 2015
- Penn Medicine News: Genetically Modified "Serial Killer" T ... - October 29th, 2015
- Beta cell regeneration - Center for Regenerative Medicine ... - October 29th, 2015
- The Stem Cell Theory of Cancer - Stanford Medicine Center - October 29th, 2015
- What is a cell? - Genetics Home Reference - October 16th, 2015
- Cell Therapy & Regenerative Medicine - University of Utah ... - October 13th, 2015
- Sickle Cell Anemia: Learn About SCD Symptoms and Treatment - September 26th, 2015
- Research - Stem Cell Biology and Regenerative Medicine ... - September 26th, 2015
- Sickle Cell Disease (Sickle Cell Anemia ... - MedicineNet - September 26th, 2015
- T Cell Therapy (CTL019) | The Children's Hospital of ... - September 15th, 2015
- Knoepfler Lab Stem Cell Blog | Building innovative ... - September 10th, 2015
- Cell culture - Wikipedia, the free encyclopedia - September 6th, 2015
- What are the potential uses of human stem cells and the ... - August 17th, 2015
- One type of airway cell can regenerate another lung cell type - April 13th, 2015
- Limber Lungs: One Type of Airway Cell Can Regenerate Another Lung Cell Type - April 13th, 2015
- Regenestem Network Announces Plans to Attend the 23rd Annual World Congress on Anti-Aging Medicine May 7-9, 2015 - April 6th, 2015
- 'Open' stem cell chromosomes reveal new possibilities for diabetes - April 3rd, 2015
- Key mechanism identified in tumor-cell proliferation in pediatric bone cancers - April 3rd, 2015
- UCI team gets $5 million to create stem cell treatment for Huntington's disease - March 28th, 2015
- Sungduan: Growth factors - March 28th, 2015
- Cleveland Clinic Researchers First to Demonstrate Significant Blocking of Opioid Tolerance With Mesenchymal Stem Cell ... - March 25th, 2015
- Johns Hopkins Medicine, based in Baltimore, Maryland - March 23rd, 2015
- stem cell medicine Jakarta tangerang serpong bsd bintaro - Video - March 21st, 2015
- Global Stem Cells Group to Hold Practical Adipose-Derived Stem Cell Harvesting, Isolation and Re-integration Training ... - March 20th, 2015
- Boston Stem Cell Biotech Start-up Asymmetrex Will Present Essential Technologies for Stem Cell Medical Engineering at ... - March 18th, 2015
- A Single-Cell Breakthrough: newly developed technology dissects properties of single stem cells - March 18th, 2015
- BrainStorm Cell Therapeutics to Present at 3rd Annual Regen Med Investor Day on March 25 in New York - March 18th, 2015
- Global Stem Cells Group to Participate in the 25th Argentine Congress of Aesthetic Medicine in Buenos Aires April 9-10 ... - March 17th, 2015
- Boosting A Natural Protection Against Alzheimer's Disease - March 13th, 2015
- Media portray unrealistic timelines for stem cell therapies - March 12th, 2015
- Stem cells lurking in tumors can resist treatment - March 12th, 2015
- Building custom blood cells to battle sickle cell disease - March 11th, 2015
- Johns Hopkins researchers engineer custom blood cells - March 10th, 2015
- Targazyme Inc. Receives Orphan Drug Designation to TZ101 for Use With Regulatory T Cells to Prevent & Reduce the ... - March 10th, 2015
- Mast cell - Wikipedia, the free encyclopedia - March 9th, 2015
- Achieving gender equality in science, engineering and medicine - March 9th, 2015
- Seven strategies to advance women in science - March 9th, 2015
- British biotech firm sets crowdfunding record with heart drug - March 9th, 2015
- A good night's sleep keeps your stem cells young - March 9th, 2015
- Howe's recovery shows stem-cell advances - March 1st, 2015
- Translational Regenerative Medicine: Market Prospects 2015-2025 - February 28th, 2015
- Stem cellrecruiting hydrogels based on self-assembling peptides for tissue regeneration - February 25th, 2015
- Sertoli cell - Wikipedia, the free encyclopedia - February 17th, 2015
- Global Stem Cells Group Announces Alliance with Regenerative Technology - February 11th, 2015
- Biotech firm Cell Therapy claims crowdfunding record with heart drug - February 10th, 2015
- Two UC San Diego Scientists Receive Stem Cell Technology Grants - February 3rd, 2015
- Regenestem Network and Gilberto Hernandez Falcon, M.D. Open Stem Cell Clinic in Yucatan - January 31st, 2015
- Global Stem Cells Group and Regenestem Network Announce Launch of New Stem Cell and Regenerative Medicine Clinic in ... - January 29th, 2015
- Asymmetrex Scheduled to Present Unique Perspectives in Stem Cell Biology and Recent Advances in Technologies for Adult ... - January 29th, 2015
- Gordie Howe's stem cell therapy raises concerns among medical experts - January 29th, 2015
- Gordie Howe's stem cell therapy raises concerns among experts - January 29th, 2015
- BioTime Announces Issuance of 14 New Patents in the Fields of Regenerative Medicine, Stem Cell Technology, and Cancer ... - January 27th, 2015
- Keeping the Kraken asleep - January 27th, 2015
- Helmholtz International Fellow Award for Prof. Amanda Fisher from London - January 27th, 2015
- Regenestem Network, a division of Global Stem Cells Group, Announces Launch of New Stem Cells and Regenerative ... - January 22nd, 2015
- Scientists announce revolutionary culturing technique for liver and pancreas - January 22nd, 2015
- New Type of Cell Found to Repair Lung Injury in Mice - January 18th, 2015
- Stem cells derived from amniotic tissues have immunosuppressive properties - January 16th, 2015
- Global Stem Cells Group to Move Headquarters to Larger Miami Lakes Office Complex - January 14th, 2015
- Peter S. Kim Named the Virginia and D.K. Ludwig Professor of Biochemistry at Stanford - January 13th, 2015
- Renowned professor's book addresses stem cell biology & regenerative medicine - January 13th, 2015
- Circadian rhythms regulate skin stem cell metabolism and expansion, study finds - January 7th, 2015
- Cord Blood Banking Leader, Cryo-Cell International, Continues to Support the Advancement of Regenerative Medicine - January 6th, 2015
- Scientists Develop Pioneering Method to Define Stages of Stem Cell Reprogramming - January 6th, 2015
- Pioneering method developed to define stages of stem cell reprogramming - January 6th, 2015
- The Irvine Stem Cell Treatment Center Announces Adult Stem Cell Public Seminars in Orange County, California - January 5th, 2015
- Ten years in, California's stem cell program is getting a reboot - January 4th, 2015
- Two-thirds of cancer cases are "bad luck," study says - January 1st, 2015
- 'Bad Luck' of Random Mutations Plays Predominant Role in Cancer, Study Shows - January 1st, 2015