Scientists have now provided a conclusive demonstration of their huge therapeutic potential with the production of stem cells from human skin and the Nobel Prize for Physiology and Medicine: stem cells have had a fantastic year. A humanized sickle cell anaemia mouse model has been successfully treated with a combination of gene and cell therapy, as reported in the online advanced edition of Science.

By using a retrovirus to insert four transcription factor genes into the cells, human, monkey and mouse skin cells can be developmentally reprogrammed in vitro into induced pluripotent stem cells (iPS). Any of the specialized cell types that are present in the body can be created from the iPS cells. Using gene therapy in order to correct any disease causing mutations, the cells can also be genetically reprogrammed in vitro. Then before transplantation back into the patient, the cells can be differentiated into the appropriate cell type. By avoiding issues of immune-mediated tissue rejection since the cells are derived from the patient, the therapeutic potential is huge.

Mouse hemoglobin genes were replaced with human counterparts, with the homozygous sickle cell anaemia variant that causes the mice, which are called ‘knock-in’ mice, to exhibit typical symptoms of the disease. iPS cells were created with skin cells that were removed from the mice. The cells were differentiated into hematopoetic (blood) progenitor cells before being transplanted back into the mice, but first, the sickle cell mutation in the genome of these cells was then corrected by gene targeting. The red blood cell count had returned to within the normal range with significantly fewer misshapen cells after 12 weeks. The iPS cells also were responsible for for producing around 70% of the peripheral blood cells present in the mice. The treatment also substantially reduced the problems with renal function associated with sickle cell anemia.

While avoiding any tricky ethical snares by using iPS instead of embryonic stem cells, the study underlines the therapeutic potential of stem cells combined with gene therapy. With further refinement, the technology could potentially be used in humans as well.

Practicing tricks on his skateboard and attempting new wrestling moves while jumping of his couch last night, six-year-old Bretton Kinslow is not unlike other boys his age.

But the similarities end at the activities. Bretton is waiting on news that there’s a stem-cell match for the grade school student in his family’s Hatchet Lake home. His parents sit by the phone waiting for a call from Sick Kids Hospital in Toronto.

Zachary Hall, Bretton’s brother, was killed at the age of ten last year by the same genetic disease Bretton was diagnosed with on November 8th.

Causing damage to the myelin sheath that insulates the nerve cells in the brain, Adrenoleukodystrophy or ALD is a rare disease that was depicted in the 1992 film Lorenzo’s Oil.

Men are most severely affected since the most common type of ALD is linked to the x-chromosome. And men, with only one x-chromosome, are at a disadvantage.

Leading to dementia, blindness, loss of co-ordination, deafness, and ultimately death, a progressive deterioration of the nervous system characterizes the condition. Young boys are the most common victims.

Zach’s mother Lisa Kinslow knew it was too late by the time doctors realized what was wrong.

The IWK kept a close eye on Bretton after he became sick.

“They monitored Bretton every six months,” Kinslow said.

It was confirmed Bretton had developed ALD at his last six-month checkup.

Now he is waiting for a stem cell transplant. The cells will come from either bone marrow, or a umbilical cord blood.

Hopefully staving off the deterioration of his nervous system, the transplant will renew every cell in Bretton’s body.

“He won’t even have the same blood type anymore,” Kinslow said.

Kinslow and her husband Mark explained that Bretton has a better chance than his older brother who was diagnosed too late, but that there were no guarantees that the transplant would work. Meanwhile, Bretton showed off for the photographer, bouncing on and off the couch.

“With Zach, it was different; we knew the outcome,” she said.

“With this one, we’re fighting for it.”

Kinslow said Bretton has some understanding of what’s going on.

He knows he’s probably going to lose his hair because of the chemo-therapy before transplant. He knows that he will need to take a lot of medication. And he is more than aware of the doctors that surround him, trying to make him feel better, every time he goes to Toronto.

At one point last night, grinning and rubbing his head he exclaimed, “I don’t want to be bald.”

It’s been difficult for the family admitted Kinslow.

She’s trying not to let his illness become a focus, trying to keep things normal for Bretton.

“We spend every day with him, we play with him, we talk with him,” she said.

“There’s nothing that he wants to do that we don’t try.”

Proving in principle that a new form of stem cell could be used as a therapy, on Thursday, U.S. researchers treated mice with sickle cell anemia using the cells which were made from ordinary skin cells.

Possessing the same characteristics as embryonic stem cells, skin cells were reprogrammed by Japanese and U.S. researchers last month. The cells were named “iPS” cells, short for “induced pluripotent stem cells”.

Using mouse skin cells, the Japanese researchers had initially accomplished the same feat prior to using human skin cells.

A defect in a single gene causes the blood disease called sickle cell anemia. Mice were engineered to have this condition by a research team at the Whitehead Institute of Biomedical Research in Cambridge, Massachusetts. They team successfully treated these mice withe the new iPS cells.

“This is the first evaluation of these cells for therapy,” said Dr. Jacob Hanna, who worked on the study. “The field has been working for years on strategies to generate customized stem cells,” he added in a telephone interview.

Hanna said that the need for immune suppression or donor matching would be eliminated by creating stem cell therapies from a person’s own cells since that would make them genetically identical.

“Now, with the breakthrough of this new method for generating stem cell-like cells, can we try to substitute a diseased tissue in a living animal?”

Four genes were inserted into the mice skin cells by Hanna and colleagues working in Rudolf Jaenisch’s lab at Whitehead Institute. This action transformed them into iPS cells.

“We call it the magic four factor,” Hannah said.

Cells that can morph into any type of cell in the human body are called multipurpose or pluripotent. Examples of these cells are embryonic stem cells and the new iPS cells.

The researchers substituted the faulty gene that causes sickle cell anemia with a working one after coaxing these mouse master cells into becoming blood-forming stem cells.

The journal Science reported on Friday that tests showed normal blood and kidney function after the scientists transplanted these cells into the diseased 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,” Jaenisch said in a statement.

Still, much work remains in order to perfect the technique.

A type of virus called a retrovirus is used to deliver the four genes needed to turn skin cells into master cells.

“Once they enter the genome, there is the danger that they can silence some genes that are important or they can activate some dangerous genes that shouldn’t be activated,” Hanna said.

c-Myc, which is one of the genes, is known to cause cancer, and this presents another obstacle for researchers to overcome.

After the gene had completed it’s task of transforming the skin cells into iPS cells, Hanna and colleagues actually removed the c-Myc gene to get around the potential problem.

The new technique will make stem cells much easier to study. Spinal injuries, Parkinson’s disease, diabetes, and other conditions could all be treated someday using the new iPS cells.

The progressive degeneration of brain cells known as dopamine (DA) cells eventually leads to the condition called Parkinson’s disease (PD).

A promising therapeutic strategy may be the replacement of these cells. Despite the promising results observed in clinical trials, limited availability of human fetal mesencephalic tissue means that other sources of these cells are needed for routine DA cell–replacement therapy to be a possible.

Now, a new source for DA cells that provided marked benefit when transplanted into mice with a PD-like disease has been identified by Ernest Arenas and colleagues at the Karolinska Institue, Sweden.

By culturing them in the presence of a number of factors — FGF2, sonic hedgehog, and FGF8 — and engineering them to express Wnt5a, DA cells were derived from ventral midbrain (VM) neural stem cells/progenitors.

In contrast to the conventional FGF2 treatment, the new protocol produced 10-fold more DA cells. Further examination revealed that when transplanted into mice with PD-like disease, the cells initiated substantial cellular and functional recovery.

Embryonic stem cells have been eliminated as a potential source of DA cells due to their tendency to become cancerous. Using non-embryonic cells, the mice in the study did not develop tumors. The study results suggest that individuals with PD may be safely and efficiently treated with Wnt5a-treated neural stem cells.

The December 3rd issue of the Journal of Clinical Investigation has published the results of the study in an article titled, “Wnt5a-Treated Midbrain Neural Stem Cells Improve Dopamine Cell Replacement Therapy in Parkinsonian Mice”.

By restoring the decaying brain cells of a 65-year-old to the levels of an 18-year-old, Australian scientists believe they have cracked the code to preventing dementia.

Dementia is a group of degenerative brain disorders that includes Alzheimer’s disease. More than 200,000 Australians suffer from these conditions, but new hope may be on the way in the form of breakthroughs which were presented to pharmaceutical chiefs at a closed event last week.

Facilitating the boost of mental functions such as understanding and memory, the scientists have developed two ways to stimulate stem cells and regenerate the brain.

Increasing the number of stem cells in young and middle-aged brains could help stave off dementia according to leading stem cell scientist Dr. Rod Rietze and his team at the University of Queensland.

“The idea is not to transplant anything