One big step for Geron: Therapy that enabled paralyzed rats to walk ready for test on humans, stem-cell firm says

February 24, 2008

(Editor's note: This will have implications for Dejerine-Sottas research in the future:)

Using human embryonic stem cells, the Menlo Park company has developed a therapy that enables paralyzed rats to walk and that it claims shows no dangerous side effects in experiments with about 2,000 animals.
Others also are studying such cells for medical uses, including Stanford University scientists, who last week said they had used them to help stroke-disabled lab rats walk better. But none are as close to seeking permission for human tests as Geron, whose treatment is for spinal injuries.

For its application requesting regulatory approval from the U.S. Food and Drug Administration, the public company has gathered 25,000 pages of data - far more than normal for such requests, Geron Chief Executive Dr. Thomas Okarma said. He told analysts recently that Geron would submit it to the FDA during the first part of this year. But he declined to reveal the actual filing date, he said, "to minimize any kind of pressure on the agency."

Yet Geron's bid isn't certain.

Although the FDA would not comment on Geron's application, President Bush objects to most research with embryonic stem cells, which come from discarded embryos. Moreover, his administration has become intrigued with recent studies showing skin cells can be manipulated to have embryonic-like properties without harming an embryo.

Read the rest of One Big Step for Geron.

Bone Marrow Cell Transplants Help Nerve Regeneration

December 05, 2007

ScienceDaily (Dec. 5, 2007) — A study carried out by researchers at the Kyoto University School of Medicine has shown that when transplanted bone marrow cells (BMCs) containing adult stem cells are protected by a 15mm silicon tube and nourished with bio-engineered materials, they successfully help regenerate damaged nerves. The research may provide an important step in developing artificial nerves.

"We focused on the vascular and neurochemical environment within the tube," said Tomoyuki Yamakawa, MD, the study's lead author. "We thought that BMCs containing adult stem cells, with the potential to differentiate into bone, cartilage, fat, muscle, or neuronal cells, could survive by obtaining oxygen and nutrients, with the result that rates of cell differentiation and regeneration would improve."

Nourished with bioengineered additives, such as growth factors and cell adhesion molecules, the BMCs after 24 weeks differentiated into cells with characteristics of Schwann cells -- a variety of neural cell that provides the insulating myelin around the axons of peripheral nerve cells. The new cells successfully regenerated axons and extended their growth farther across nerve cell gaps toward damaged nerve stumps, with healthier vascularity.

"The differentiated cells, similar to Schwann cells, contributed significantly to the promotion of axon regeneration through the tube," explained Yamakawa. "This success may be a further step in developing artificial nerves."

Read more of Bone Marrow Cell Transplants Help Nerve Regeneration

Skin stem cells aid nerve cells

June 16, 2006

Researchers are one step closer to repairing nerve cells and treating conditions such as spinal cord injury, Parkinson's disease and multiple sclerosis.

A new study says that stem cells found in adult skin can function after being transplanted into diseased mice.

"This shows that these stem cells found in adult skin are the real thing. We saw it in the culture dish, but now we know it's the bona-fide real thing," said an elated Dr. Freda Miller, senior scientist at Sick Kids hospital.

The research found that these stem cells, called skin-derived precursors or SKPs, can produce nervous system cell types called Schwann cells. These cells in turn make insulation, or myelin, and allow nerve cells to function efficiently. [Toronto Sun]

Study: Stem cells may repair spinal cord damage

September 21, 2005

Very exciting news about the potential of stem cells for myelin regeneration.

Injections of human stem cells seem to directly repair some of the damage caused by spinal cord injury, according to research that helped partially paralyzed mice walk again.

The experiment, reported Monday, isn't the first to show that stem cells offer tantalizing hope for spinal cord injury--other scientists have helped mice recover, too.

But the new work went an extra step, suggesting the connections that the stem cells form to help bridge the damaged spinal cord are key to recovery.

Surprisingly, they didn't just form new nerve cells. They also formed cells that create the biological insulation that nerve fibers need to communicate. A number of neurological diseases, such as multiple sclerosis, involve loss of that insulation, called myelin.

Scientists make nerve stem cells

August 18, 2005

The world's first pure nerve stem cells made from human embryonic stem cells has been created by scientists at the Universities of Edinburgh and Milan. [BBC]

Nano World: Nano for stem-cell research

June 15, 2005

From The Washington Times: Cutting-edge nanotechnology is beginning to help advance the equally pioneering field of stem-cell research, with devices that can precisely control stem cells and provide self-assembling biodegradable scaffolds and magnetic tracking systems, experts told UPI's Nano World.

"Nanotechnology might show people once and for all that you really can help regenerate organs with stem-cell biology and help people walk again, help people after heart attacks, help people after stroke," said John Kessler, a neurologist at Northwestern University in Evanston, Ill.

"My own daughter had a spinal-cord injury, and the thought that I could contribute to helping my daughter with this is just overwhelmingly exciting to me," Kessler added.

Stem cells are the primordial cells of the body; every other cell type originates from them. Embryonic stem cells have the power to become any other type of cell, while adult stem cells--those collected from adults, children or umbilical cords--only can become certain kinds of cells, such as blood or fat. Scientists hope to create new therapies based on stem-cell implants that repair damaged or lost organs and tissues.

In their natural environment in the body, stem cells transform into other cell types based on chemical triggers they receive from their surroundings.

The exact cues and the placement of those cues for most stem cells are not known, "and our ability to introduce specific chemicals at select locations on a cell is extremely limited," said materials scientist Nick Melosh at Stanford University in Palo Alto, Calif.

Researchers currently must bathe the entire surface of stem cells in various chemicals to search for a response, so Melosh and colleagues are developing a nano lab--on the scale of billionths of a meter--to experiment with individual adult stem cells. Each lab essentially consists of a capsule on a silicon chip, around which up to 1,000 nanoreservoirs hold roughly a millionth of a billionth of a milliliter of liquid, comparable to the size of secretions cells use to communicate.

"We are in essence building an artificial cell-interface unit through which we can 'talk' to a stem cell, in much the same way real cells do, through chemical communication," Melosh said. "Nanotechnology is essential for this project. Larger systems just couldn't provide the number of different reservoirs and chemicals within a space small enough to select different areas on a cell."

Future nerve-damage repairs could be accomplished with the aid of stem cells grown in self-assembling three-dimensional biodegradable scaffolds of nanofibers developed by Sam Stupp, a materials scientist working with Kessler at Northwestern.

"When you have nerve fibers try to grow out in the spinal cord, they need something to grow on," Kessler said. "This scaffold gives them physical material to grow across, hang onto."

The fibers, delivered in liquid form, self-assemble into a scaffold within seconds of making contact with the electrically charged ions surrounding cells. An amino acid in the fibers helps promote the growth of neurites--branches extending from nerves that help the cells communicate. The scaffolds then dissolve as cells grow into place.

Kessler said the preliminary work on repairing spinal-cord damage in mice and rats with neural-progenitor cells is proceeding well. The fibers apparently help prevent the cells from developing into scar tissue around damaged nerves.

"It's important to stress that by no means do we have a treatment for spinal-cord injury yet in humans," he cautioned.

Stupp has established Nanotope, a startup company in Evanston, to bring a product based on the nanoscaffold concept to human trials. Kessler said the scaffolds also could help regenerate "many other organs of the body."

Douglas Kniss, a stem-cell biologist at Ohio State University in Columbus, and colleagues also are developing nanofibrous scaffolds for stem cells.

"The non-cell part of a tissue--the matrix between the cells--is important (and) can affect cell function," Kniss explained. "With nanofiber scaffolds, you mimic the nanometer-scale fibers normally found in that matrix. This research could help (address) the critical shortage of transplantable organs."

His team is creating biodegradable scaffolds to nurture fat stem cells. During tumor surgery, doctors often extract fat cells from other parts of the body and transplant them into the tissue from where the tumor was removed.

"You often have scars from donating portions of the body; instead, you can have new fat tissue used in reconstituting those defects," Kniss said.

Kniss and colleagues are developing non-biodegradable three-dimensional scaffolds to hold stem cells for pharmaceutical and biological research.

"You can develop these tissue constructs to test new drugs," he said. "Tissues grow in three dimensions and not two, and three dimensions would be more advantageous for early drug screening."

In the future, magnetic iron-oxide nanoparticles could help physicians ensure they are implanting therapeutic stem cells in the correct location.

"If you inject them in the wrong place, you might inject them into dead tissue, and they would die right away with no nutrients," explained Jeff Bulte, a magnetic-resonance-imaging researcher at The Johns Hopkins University School of Medicine in Baltimore.

In animal tests, researchers have had to remove tissue in order to pinpoint where they implanted stem cells. Using MRI has the potential to track stem cells non-invasively in living animals, but stem cells normally do not easily absorb the magnetic particles doctors inject to enhance MRI scans.

"You need to get a high number of the particles into cells, since the sensitivity of MRI is not very high," Bulte said.

In 2001 Bulte and colleagues reported the first success in MRI tracking of stem cells using magnetic nanoparticles carried into the cells via branch-like nanostructures called dendrimers. Now, he said, the process does not even need dendrimers. Instead, it employs electric pulses that briefly open up pores in stem-cell surfaces, allowing the magnetic nanoparticles to leak in.

"The beauty of it is that it just takes a second. You just mix the nanoparticles with the cells and press a button," he said.

Now Bulte is partnering with two of his Hopkins colleagues--veterinary radiologist Dara Kraitchman and cardiologist Joshua Hare--to tag magnetically stem cells implanted in heart-attack patients in the hopes of gaining insights into repairing heart damage.

Support the Stem Cell Research Enhancement Act

February 06, 2005

This just in from the Christopher Reeve Action Network:

Good News: We have a pro-stem cell bill. Let’s get behind it!

The first 100 Days of 2005 are critical for stem cell research and somatic cell nuclear transfer (SCNT or therapeutic cloning). Representatives Mike Castle (R-DE) and Diana DeGette (D-CO) are gearing up to re-introduce the Stem Cell Research Enhancement Act in the next few weeks and are asking for your help to build the list of co-sponsors.

This is our opportunity to advance positive legislation that would expand the current policy--announced without a national debate!--by President Bush on August 9, 2001. In recent days, there have been a number of articles written about the limited capacity of the current embryonic stem cell lines eligible for federal funding. (Click here for an article in the Los Angeles Times.) Now is the time to contact your Representative and tell them to support research and to be an original co-sponsor on the Castle-DeGette bill.

The legislation would allow federal funds to be used to conduct research on stem cells that meet the following criteria:

• Embryos were originally created for fertility treatment purposes and are in excess of clinical need;
• The individuals seeking fertility treatments for whom the embryos were created have determined that the embryos will not be implanted in a woman and will be discarded; and
• The individuals for whom the embryos were created have provided written consent for embryo donation.

In short, this bill asks for embryos that would be discarded to be used instead for research with the potential to save lives! We think this bill represents a modest and ethical way to pursue the promise of this field of study.

There is no time to waste. Please join us in our Campaign to Defend Hope:

Take action;
Spread the word; and
Help save and improve the lives of millions—let’s keep politics out of science!
Take action now. Write your Members of Congress and ask them to proactively support upcoming legislation that would give hope and support scientific research.

Urge Your Senators and Representative to Support Research!

The Christopher Reeve Action Network
We Must. We Can. We Will.

Christopher Reeve Paralysis Foundation
500 Morris Avenue, Springfield, NJ 07081
(800) 225-0292

www.ChristopherReeve.org

One step closer

January 31, 2005

From Scientific American: Scientists Switch Stem Cells into Neurons

Su-Chun Zhang of the University of Wisconsin-Madison and his colleagues exposed human embryonic stem cells to a variety of growth factors and hormones in sequence in order to encourage them to change into motor neurons. "You need to teach the [embryonic stem cells] to change step by step, where each step has different conditions and a strict window of time," Zhang explains. "Otherwise, it just won't work." The embryonic stems cells first became neural stem cells then changed into the beginnings of motor neurons before finally differentiating into spinal motor neuron cells, the cell type that, in the human body, transmits messages from the brain to the spinal cord. The newly generated motor neurons exhibited electrical activity, the signature action of neurons, and survived in culture for more than three months.

This is a very positive step, but many obstacles remain before this can be turned into a treatment. These cells were grown in a lab, and getting them into someone in the right place and having them function is an entirely different problem. So while it's too early to break out the champagne, we can permit ourselves a little happy dance.

Reinnervation research from The Miami Project to Cure Paralysis

December 24, 2004

Thanks again to CMTUS for this interesting article about current stem cell based reinnervation research. Looks promising! Click more to read the rest.

Abstract from Neuroscience. 2005;130(3):619-30

The immunophilin ligand FK506, but not the P38 kinase inhibitor SB203580, improves function of adult rat muscle reinnervated from transplants of embryonic neurons.

Grumbles RM, Casella GT, Rudinsky MJ, Godfrey S, Wood PM, Thomas CK.

The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami School of Medicine, Lois Pope Life Center, 1095 NW 14(th) Terrace (R48), Miami, FL 33136 USA.

Injury to the adult CNS often involves death of motoneurons, resulting in the paralysis and progressive atrophy of muscle. There is no effective therapy to replace motoneurons in the CNS. Our strategy to replace neurons and to rescue denervated muscles is to transplant dissociated embryonic day 14-15 (E14-15) ventral spinal cord cells into the distal stump of a peripheral nerve near the denervated muscles. Here, we test whether long-term delivery of two pharmacological inhibitors to denervated muscle, FK506 or SB203580, enhances reinnervation of muscle from embryonic cells transplanted in the tibial nerve of adult Fischer rats. FK506, SB203580 (2.5 mg/kg) or saline was delivered under the fascia of the medial gastrocnemius muscle for 4 weeks, beginning when muscles were denervated by section of the sciatic nerve.

After 1 week of nerve degeneration, one million E14-15 ventral spinal cord cells were transplanted into the distal tibial nerve stump of each rat in the three treatment groups. Ten weeks later, all cell transplants had neuron-specific nuclear protein (NeuN) positive neurons. Neuron survival and axon regeneration were similar across treatments. An average (+/-S.E.) of 210+/-66, 100+/-36 and 176+/-58 myelinated axons grew distally from the cell transplants of rats with muscles treated with FK506, SB203580 or saline, respectively. Regenerating axons in muscles of all three treatments groups were detected with antibodies against phosphorylated neurofilaments and synaptophysin, and motor end plates were labeled with alpha-bungarotoxin. Muscles of rats that received transplants of media only had no axon growth, indicating that the muscles were denervated. The mean muscle fiber areas of rats that received cell transplants and had long-term delivery of FK506, SB203580 or saline to muscles were significantly larger than those of denervated muscle fibers.

Thus, cell transplantation reduced muscle atrophy. Transplantation of embryonic cells also resulted in functional muscle reinnervation. Electromyographic activity and force were evoked from >90% of the muscles of rats with cell transplants, but not from denervated muscles.

FK506-treated muscles were significantly more fatigue resistant than naive control muscles. FK506-treated muscles also had significantly stronger motor units than those in SB203580 or saline-treated muscles. These data suggest that a pathway regulated by FK506 improves the function of muscles reinnervated by embryonic neurons placed in peripheral nerve.

Action Alert: House to vote on Weldon Bill

February 15, 2003

The House of Representatives will be voting on Congressman Dave Weldon?s (R-FL) legislation - The Human Cloning Prohibition Act of 2003 as early as February 25th.

The bill would ban all forms of cloning, including somatic cell nuclear transfer, also called therapeutic cloning. Therapeutic cloning is vital to the development of new therapeutics that could assist millions of Americans. Congressman Weldon?s bill criminalizes the very biomedical research that may provide the best hope to finding cures for Alzheimer?s disease, ALS, diabetes, various cancers, strokes, Parkinson's disease, traumatic brain injuries, and spinal cord injuries. We all agree, human reproductive cloning is unsafe and unethical; CAMR has repeatedly called on Congress to enact a ban on human reproductive cloning. However, a ban on therapeutic cloning would only dash the hopes of millions of Americans suffering from deadly and debilitating diseases.

H.R. 801, an alternative bill, has been introduced by Representatives Jim Greenwood (R-PA), Peter Deutsch (D-FL), Diana DeGette (D-CO), Anna Eshoo (D-CA), and Mark Kirk (R-IL). This would allow research using therapeutic cloning, while maintaining the same criminal penalties of Congressman Weldon's bill. Congressman Greenwood will try and offer this bill as a substitute during the House debate. Tell your Representative to vote NO on H.R. 534 and to instead support research and vote YES on H.R. 801.

Somatic cell nuclear transfer is about saving and improving lives. Go to www.camradvocacy.org, and follow the steps to contact Congress.

MS damage repaired by stem cells

January 23, 2003

Scientists have successfully regenerated myelin in the brains of mice with Multiple Sclerosis. The stem cells were able to home in on areas of recent damage, and convert into oligodendrocytes - cells that manufacture myelin. This doesn't solve the problem of getting stem cells to peripheral nerves, but it's another step in the right direction.

Pre-treating stem cells turns them into neurons

November 13, 2002

Scientists have made another breakthrough in stem cell research, bringing us a step closer to treatments for neurodegenerative diseases and spinal cord injuries.

Previous attempts to replace damaged nerve cells have failed, with only a few cells developing into neurons.

By treating the stem cells with chemicals, the scientists succeeded in changing them into neurons.

It's Now Ok for Republicans to Favor Stem Cell Research

September 30, 2002

Nancy Reagan has quietly come out in favor of federal financing for embryonic stem cell research. "A lot of time is being wasted," she told a friend. "A lot of people who could be helped are not being helped." Former President Ronald Reagan's Alzheimer's has worsened to the point where he no longer recognizes her, and embryonic stem cells may potentially hold the key to a cure.

Says Republican Senator Arlen Specter, "She's a former first lady, she holds a special position because of her own persuasive personality, and her husband, President Reagan, has Alzheimer's... she's a triple threat."

California defies Bush on stem cells

September 24, 2002

Often at odds with the rest of the country, California has taken a pro-stem cell research stand, adopting a law permitting embryos to be both donated and destroyed for research with written consent. California Governor Gray Davis was joined at the new law's announcement by Christopher Reeve, who recently openly blasted Bush for blocking stem cell research.

Reeve Speaks Out

September 17, 2002

Christopher Reeve rips Bush and the Catholic Church for opposing research that could someday lead to cures, not only for paralysis, but for many of the diseases that continue to plague the human race.

Note to Bush: don't mess with Superman.

This week in New Scientist

September 01, 2002

A controversial stem cell bank is set to open soon in England, in order to harvest and store both adult and embryonic stem cell lines for future use. There's also an interesting article about using functional electrical stimulation to treat hemiplegia. FES research could have ramifications for DS someday.

Stem cell research far from booming

August 24, 2002

(As seen on DMDoptions.com.) The Washington Post reports that stem cell research in the U.S. isn't exactly booming, due primarily to the fact that only three colonies of embryo cells are readily available to researchers.

Can we get moving here, people?

Outlook for US stem cell research brightens

August 15, 2002

The US government quietly released a clarification of Bush's restrictive policy on stem cell research - making it far less restrictive than feared. And a $5 million grant has been announced to the University of California, San Francisco, in order to pursue research into stem cell applications. Things are looking up!

http://www.newscientist.com/news/news.jsp?id=ns99992655