Reprogrammed adult cells treat sickle-cell anemia in mice

December 6, 2007

Mice with a human sickle-cell anemia disease trait have been treated successfully in a process that begins by directly reprogramming their own cells to an embryonic-stem-cell-like state, without the use of eggs. This is the first proof-of-principle of therapeutic application in mice of directly reprogrammed “induced pluripotent stem” (IPS) cells, which recently have been derived in mice as well as humans.

The research, reported in Science Express online on December 6, was carried out in the laboratory of Whitehead Member Rudolf Jaenisch. The IPS cells were derived using modifications of the approach originally discovered in 2006 by the Shinya Yamanaka laboratory at Kyoto University.

The scientists studied a therapeutic application of IPS cells with the sickle-cell anemia model mouse developed by the laboratory of Tim Townes of the University of Alabama at Birmingham. Sickle-cell anemia is a disease of the blood marrow caused by a defect in a single gene. The mouse model had been designed to include relevant human genes involved in blood production, including the defective version of that gene.

To create the IPS cells, the scientists started with cells from the skin of the diseased mice, explains lead author Jacob Hanna, a postdoctoral researcher in the Jaenisch lab. These cells were modified by a standard lab technique employing retroviruses customized to insert genes into the cell’s DNA. The inserted genes were Oct4, Sox2, Lif4 and c-Myc, known to act together as master regulators to keep cells in an embryonic-stem-cell-like state. IPS cells were selected based on their morphology and then verified to express gene markers specific to embryonic stem cells. To decrease or eliminate possible cancer in the treated mice, the c-Myc gene was removed by genetic manipulation from the IPS cells.

Next, the researchers followed a well-established protocol for differentiating embryonic stem cells into precursors of bone marrow adult stem cells, which can be transplanted into mice to generate normal blood cells. The scientists created such precursor cells from the IPS cells, replaced the defective blood-production gene in the precursor cells with a normal gene, and injected the resulting cells back into the diseased mice.

The blood of treated mice was tested with standard analyses employed for human patients. The analyses showed that the disease was corrected, with measurements of blood and kidney functions similar to those of normal mice.

“This demonstrates that IPS cells have the same potential for therapy as embryonic stem cells, without the ethical and practical issues raised in creating embryonic stem cells,” says Jaenisch.

While IPS cells offer tremendous promise for regenerative medicine, scientists caution that major challenges must be overcome before medical applications can be considered. First among these is to find a better delivery system, since retroviruses bring other changes to the genome that are far too random to let loose in humans. “We need a delivery system that doesn’t integrate itself into the genome,” says Hanna. “Retroviruses can disrupt genes that should not be disrupted or activate genes that should not be activated.”

Potential alternatives include other forms of viruses, synthesized versions of the proteins created by the four master regulator genes that are modified to enter the cell nucleus, and small molecules, Hanna says.

Despite the rapid progress being made with IPS cells, Jaenisch emphasizes that this field is very young, and that it’s critical to continue full research on embryonic stem cells as well. “We wouldn’t have known anything about IPS cells if we hadn’t worked with embryonic stem cells,” says Jaenisch. “For the foreseeable future, there will remain a continued need for embryonic stem cells as the crucial assessment tool for measuring the therapeutic potential of IPS cells.”

Source: Whitehead Institute for Biomedical Research

4.3 /5 (9 votes)  

Rank 4.3 /5 (9 votes)
Tags

Relevant PhysicsForums posts
  • Is Everyday Technology Killing Us?
    createdFeb 08, 2012
  • Exercise and weight loss
    createdFeb 08, 2012
  • Why do we have head aches? Our brains can't feel anything.
    createdFeb 07, 2012
  • "The end of diseases" by David Agus, interview from Daily Show with Jon Stewart
    createdFeb 04, 2012
  • Oncolytic adenovirus
    createdFeb 04, 2012
  • Nutrition label stuffs and diets
    createdFeb 02, 2012
  • More from Physics Forums - Medical Sciences

More news stories

FDA-approved drug rapidly clears amyloid from the brain, reverses Alzheimer's symptoms in mice

Neuroscientists at Case Western Reserve University School of Medicine have made a dramatic breakthrough in their efforts to find a cure for Alzheimer's disease. The researchers' findings, published in the journal Science, show t ...

Medicine & Health / Neuroscience

created 13 hours ago | popularity 4.9 / 5 (34) | comments 14 | with audio podcast

Anyone can learn to be more inventive, cognitive researcher says

There will always be a wild and unpredictable quality to creativity and invention, says Anthony McCaffrey, a cognitive psychology researcher at the University of Massachusetts Amherst, because an "Aha moment" is rare and ...

Medicine & Health / Psychology & Psychiatry

created 9 hours ago | popularity 4.7 / 5 (7) | comments 1 | with audio podcast

Researchers weigh in on ethics of H5N1 research

(Medical Xpress) -- In a commentary on the biosecurity controversy surrounding publication of bird flu research details, a bioethicist and a vaccine expert at Johns Hopkins reaffirm that "all scientists have an affirmativ ...

Medicine & Health / Other

created 12 hours ago | popularity not rated yet | comments 0 | with audio podcast

Cell biologists describes mechanism by which some people may be more susceptible to colon cancer

An international research team led by cell biologists at the University of California, Riverside has uncovered a new insight into colon cancer, the third leading cause of cancer-related deaths in the United ...

Medicine & Health / Cancer

created 10 hours ago | popularity 5 / 5 (3) | comments 0 | with audio podcast

To perform with less effort, practice beyond perfection

Whether you are an athlete, a musician or a stroke patient learning to walk again, practice can make perfect, but more practice may make you more efficient, according to a surprising new University of Colorado Boulder study.

Medicine & Health / Neuroscience

created 12 hours ago | popularity 4.6 / 5 (9) | comments 3 | with audio podcast


'Dark plasmons' transmit energy

Microscopic channels of gold nanoparticles have the ability to transmit electromagnetic energy that starts as light and propagates via "dark plasmons," according to researchers at Rice University.

Hydrogen from acidic water: Researchers develop potential low cost alternative to platinum for splitting water

A technique for creating a new molecule that structurally and chemically replicates the active part of the widely used industrial catalyst molybdenite has been developed by researchers with the Lawrence Berkeley ...

Ultraviolet protection molecule in plants yields its secrets

Lying around in the sun all day is hazardous not just for humans but also for plants, which have no means of escape. Ultraviolet (UV) radiation from the sun can damage proteins and DNA inside cells, leading ...

Soraa LED light may dim 50-watt halogen rivals

(PhysOrg.com) -- Soraa, a Fremont, California company founded in 2008, this week launched its first product, a light that uses LEDS (light emitting diodes). The "Soraa LED MR16 lamp" is the "perfect" replacement ...

Flexible paper robots

(PhysOrg.com) -- These inexpensive robots can stretch, bend and twist under control, and lift objects up to 120 times their own weight. Being soft, they can apply gentle and even pressure, and adapt to varied ...

Engineers find inspiration for new materials in Piranha-proof armor

(PhysOrg.com) -- It’s a matchup worthy of a late-night cable movie: put a school of starving piranha and a 300-pound fish together, and who comes out the winner?