Gene Therapy + Stem Cells = Great Therapeutic Potential

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.

Boy Waits for Stem Cell Match to Treat Adrenoleukodystrophy

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.”

Sacramento Man Treated for Spinal Injury Using Own Stem Cells

Leaving him hobbled and unable to work for nearly three years, Perry Anderson’s spine injury has changed the man’s life considerably. But stem cells are now being implanted into his spine and may work wonders in repairing his spine from a surgery that failed the first time.

The stem cells being used are not from human embryos. They come from bone marrow, and they not only have the potential to heal Perry’s spine, but the same type of cells allow diabetics to continue producing insulin, end the suffering caused be inflammatory bowel disease, and help heart attack patients heal.

Bone marrow stem cells, harvested both from cadavers and from live donors, are being developed for use against a range of illnesses. This is all while the ethical debate rages over the use of stem cells taken from discarded human embryos.

To control diseases caused by the sometimes harmful effects of the body’s own immune system these cells are proving useful in experimental drug therapies and have exhibited a remarkable ability to form fat, cartilage, ligaments, bone and tendons.

An adult stem cell-based drug is being tested at UC Davis by stem cell scientist Jan Nolta. She will be treating patients with Crohn’s, a chronic and painful bowel disease. Also using the cells in spine surgery, is the Sacramento based Dr. Pasquale Montesano.

Found in the tissue tucked inside the bone cavity are MSC’s, or mesenchymal stem cells.

Kept frozen, MSC’s can be stored for up to five years. But they must be used within 48 hours once removed in order to remain viable.

Anderson’s stem cells arrived in a tiny jar carefully packed in dry ice and stored in a foam cooler on Thursday in the operating room at Sutter Memorial Hospital in Sacramento.

Back in 2004, Anderson fell from a 6-foot ladder while he was painting. This resulted in an injured back. Searing headaches and pain were the symptoms of a bad disk pinching a nerve in his neck. In August of 2006, he had surgery to remove the damaged disk and fuse the vertebrae. But the procedure was not 100% successful.

“The headaches aren’t as bad, but my hands get numb, my arms are aching, I have lower back pain, anxiety attacks and depression,” Anderson, 42, said before his surgery Thursday. “I have worked since I was 17. Now I can’t do anything. I can’t mow the yard, I can’t go grocery shopping. It’s ridiculous.”

Careful to avoid Anderson’s carotid artery and spinal cord, Montesano first removed the scar tissue and bony fragments from between the damaged vertebrae.

He then took the crystal-like stem cell and packed them into a graft made from cadaver bone and shaped like a square nut from a hardware store. He tucked more cells around the graft after gently placing it into Anderson’s spine.

By screwing a small metal plate into his spine to anchor the bone in place while it heals, Montesano completed Anderson’s operation.

“Now we have to let Mother Nature take its course,” he said.

A handful of companies worldwide are currently taking mesenchymal stem cells from live donors in order to develop drugs. In Japan, researchers are studying the treatment of severe gum disease, England is working on multiple sclerosis, and in Iran, scientists are looking for a way to use MSC’s to treat cirrhosis.

Rationalizing the Stem Cell Debate

Stem cell research, particularly the type involving embryos, has been a hot topic responsible for a high amount of writing, discussion, and media attention as of late.

With the power to repair and even replace damaged tissue and cells, stem cells, although very meager in looks, are the most remarkable building blocks in our bodies.

Stem cells which have been derived from sources which include blood, bone marrow, fat, umbilical cord blood, nerves, adult tissue, and even the pulp of baby teeth have amassed data; proving their success in the treatment of numerous conditions and diseases.

These cells are often called “adult stem cells”. Heart damage, Parkinson’s Disease, spinal cord injury, autism, diabetes are among the nearly 80 conditions which have been successfully treated using these adult cells.

In fact, since the active ingredient in the bone marrow is stem cells, thousands of lives have been saved by adult stem cells in the form of bone marrow transplants for leukemia and other illnesses alone.

A stem cell can make any number of cells with more specialized functions, or make a copy of itself. The cell starts as an unspecified cell and changes when it divides.

For example, depending on what the body needs, white bloods cells, red blood cells, or other kinds can be created from just one type of stem cell in the human blood.

To this day, not one single human patient has ever been cured or successfully treated with embryonic stem cells, thus, it is a wonder why there is so much hype surrounding embryonic stem cell research. Especially given the fact that adult stem cells have produced such gleaming results thus far. and will undoubtedly continue to do so well into the future.

Embryonic stem cell are not only ineffective, but dangerous. In animal tests, subjects have experienced immune system rejection, formed lethal tumors, and displayed genetic instability.

At the expense of advancing adult stem cell research, why does the media, culture, and society continually support embryonic stem cell research? The scientific validity of adult stem cell being vastly superior to embryonic cells is undeniable.

The answer is green.

Money, and extremely large amounts of it are floating around embryonic stem cell research. The ongoing attempts to obtain our tax dollars for this purpose, the billions that are already invested privately, even the basic cost of donated eggs for embryonic research; all this money has been wasted thus far at the expense of advancing and producing more treatments that save human lives.

However, the current querulous embryonic stem cell debate may soon be at an end thanks to the recent announcements by Japan’s Shinya Yamanaka and James A. Thomson at the University of Wisconsin. The two scientists made two separate discoveries involving skin cells. They were able to produce embryonic stem cell equivalents without the use of an embryo.

Why continue research on such a controversial issue when such an important breakthrough has been made? Embryonic stem cell research should be a non-issue at this point.

Mice with Sickle Cell Anemia Cured with New iPS Cells

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.

Dopamine Cells Replaced by Stem Cells to Treat Parkinson’s

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”.

Supporters Growing for iPS Cell Breakthrough

Without the slightest bit of knowledge as to what is possible, probable, or even feasible, politicians will ask us to allocate billions for stem cell research. We were told that embryonic stem cells were the only answer for treating diabetes, MS, blindness, Parkinson’s, spinal cord injury, and heart disease. But the truth is that embryonic stem cells have failed in every single category. Successful treatments do exist for these conditions, but they are all derived from adult stem cells, which are non-controversial, and non-embryonic.

With what could be considered the most important medical advancement in history coming to fruition as we debate on ethics, it is sad that we don’t receive non-selective, factual, and accurate news. With all the important breakthroughs that are taking place, it is amazing that the public is being kept in the dark.

Stunning the entire research community last week, revered embryonic scientific stem cell leader Ian Wilmut (cloner of Dolly the sheep) made an announcement in support of adult stem cells over embryonic. His decision was based on solid scientific principal as opposed to religious or moral preference. Professor Wilmut has always maintained that there is a better way to accomplish the objective without destroying the embryo; in fact, he has never believed embryonic research to be unethical.

Despite the resistance of governments to fund embryonic stem cell research in the U.S. and England, the rest of the world has been conducting unrestricted research for more than ten years using embryos. Despite the joint efforts of Germany, India, Korea, Russia, and China who invested billions in research, not even one successful treatment was produced. This fact was made painfully obvious by neurologist Dr. Carlos Lima earlier this year when he was addressing the House of Lords in England.

Miracle Stem Cell Heart Repair, a breakthrough book by author/researcher Christian Wilde makes the case for adult stem cells in perhaps the most succinct manner possible.

As the author explains; “If you take the moral, political and ethical concerns off the table, the scientific issues alone confronting ESC research (according to many scientists) are in themselves, daunting. Before an ESC can be safely injected into a human being it must be proven safe in an animal study. In cases to date, animal subjects have experienced dangerous tumor growth and rejection by the body.”

He believes the public deserves balanced non-selective and un-biased reporting on both forms of stem cell research.

With a one to seven year life expectancy and 50% not making the five-year mark, heart failure is currently claiming the lives of 22 million victims world wide. Using a minimally invasive procedure using their own thigh muscle stem cells only once, patients have successfully transitioned within the FDA trials from near death to recovery. Documentation of these “no option” heart patient’s stories can be found in Miracle Stem Cell Heart Repair.

Why, asks Wilde, should it be headline world news that someday an embryonic stem cell might possibly heal a mouse heart but nowhere is there a headline that proclaims hundreds of actual living breathing people, (not mice) have already had their damaged hearts repaired with adult stem cells? Is this a case of selective reporting?

As many as five previous heart attacks were sustained by several of the patients whose stories were documented in the book.

“75% of your heart is not functioning, frankly I don’t know how you are even alive,” said one patient’s own physician.

The same patient was walking one mile and then two miles a day after six weeks and continues to do well two years after surgery following the one-time stem cell treatment with the patient’s own adult cells at the Arizona Heart Institute. The Myoheart heart failure study has now been opened to 450 more patients as treatment moves toward approval since the FDA was satisfied with the safety and clinical success of the trial’s first phase.

More than 72 diseases which included type I and II diabetes, several cancers, MS, Parkinson’s, traumatic brain injury, and blindness are currently treatable with adult stem cells. Corneal blindness is being cured at a rate of eight patients per month in Cincinnati and more than four hundred and fifty blind patients in India have been cured to date. Type II diabetes is being treated with a high rate of success inBrazil and Argentina using adult stem cells, and in similar fashion, a one-time injection of bone marrow stem cells to the pancreas as kept a type I diabetes patient in London insulin free for three years.

Following a single procedure in which stem cells from their own nasal olfactory cavity were harvested and injected into the areas of spinal lesion, one hundred five quadriplegic and paraplegic patients are beginning to walk (some with braces). Half of Dr. Lima’s patients are United States natives.

With these successes there is wonder in how anyone can argue for embryonic stem cells any more. But regardless, the debate continues. Before long, the cures will be mainstream and there won’t be a place or use for embryonic cells any longer. Perhaps that is what it will take to finally end the debate.

Japanese Goverment Allocates Funds for More Adult Stem Cell Research

Recent breakthroughs in stem cell research have produced embryonic stem cells from non-controversial adult skin cells. These same scientists are now being funded by a Japanese government agency which has decided to forge ahead with stem cell research.

Human embryos, aborted fetuses, and adult stem cells made up the only three options for stem cell research. But that is no longer the case.

After the scientists reported their amazing discovery of being able to create stem cells from human skin cells, a mere 2 weeks passed before the decision was made by the Japan Science and Technology Agency to release the funds.

Due to the fact that scientists will no longer need to create and destroy an embryo in order to extract stem cells, critics of stem cell research should tone down their protesting due to this discovery.

The cells can be used to treat many different parts of a person’s body depending on their injury or medical disease/condition. The fact that they can be converted into many different types of cell tissue after they are extracted makes the discovery particularly amazing.

The cells were converted to an embryo like state by injecting them with genes. Skin cells from the foreskin of a newborn and normal skin cells from a 36 year old woman’s face were utilized by the Japanese and U.S. research teams. Cartilage, fat, muscle, brain, and heart cells were among those that were created from the skin cells.

In order to determine if the newly programmed stem cells actually are what they appear to be more studies will be required say both research teams.

A shout has been echoing around the world due to the breakthrough.

“We’re on the way now,” said Dr. Michael Creer, director of laboratory medicine at St. Louis University and former director of the St. Louis Cord Blood Bank. “The opportunities are expanding enormously. What we think might work today could well change in the next few months … We still don’t fully understand or appreciate what is possible.”

Many people are jumping up and down with excitement with the possibility of finding treatments and cures for diseases or conditions that currently have limited treatment options. Experts say that the work is far from finished.

“People have to understand that we’re not ‘there’ yet,” said Dr. Steve Teitelbaum, a Washington University pathologist.

Significant treatments have already resulted from stem cell research. Certain eye conditions, cancer, and diabetes are among the conditions which are currently treatable using adult stem cells.

Dementia Reversed with Stem Cells

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

New Blood Forming Stem Cells Create New Immune System for Mice

Researchers used new blood forming stem cells to replace the immune systems of mice.

Creating a new immune system for people with genetic or autoimmune blood diseases by transplanting adult stem cells is the eventual goal that researchers at the Stanford University School of Medicine have taken a small but significant step towards in their mouse studies.

Effectively replacing their immune systems, the scientists found a way to transplant new blood-forming stem cells into the bone marrow of mice.

Irving Weissman, MD, a co-senior author of the study and director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine said that many aspects of the technique would need to be adapted prior to human testing.

Weissman suggested the remaining hurdles could eventually be overcome, which include the type of mice that was used which were a poor mimic of the human immune system.

The benefits have great potential when those barriers are overcome.

A person’s immune cells attacks their own body when they are afflicted with an autoimmune disease such as multiple sclerosis. Their defective immune system could potentially be replaced with an entirely new immune system that would not attack the body; an immune system transplant, live a heart or liver transplant, could be performed in order to accomplish this.

All the cells of the blood are generated by blood forming stem cells in the bone marrow. A new immune system can be created by transplanting new blood-forming cells into the bone marrow, but the defective cells must be eliminated first. Radiation or intensive chemotherapy is the typical method used to wipe out the existing system. However, increased risk of cancer, brain damage, infertility, and other tissue damage can be caused by chemotherapy while it eliminates the cells of the bone marrow. This makes the therapy inadequate, since the exchange of brain function in order to rid one’s self of multiple sclerosis is not a fair trade.

One potential path around the problem would be to eliminate only the blood-forming stem cells without affecting bone marrow cells or other tissues thought Weissman and co-first author Deepta Bhattacharya, PhD, a postdoctoral scholar in Weissman’s lab. The cells can be effectively destroyed by injecting mice with molecules that latch on to specific proteins on the surface of the blood-forming stem cells. This feat was accomplished by the team which included Agnieszka Czechowicz, first author and medical student. Without further harming the mice, the technique eliminated the blood-forming stem cells.

“It is essentially a surgical strike against the blood-forming stem cells,” said Weissman, the Virginia & D.K. Ludwig Professor for Clinical Investigation in Cancer Research.

A new blood and immune system was established after the transplanted new blood-forming stem cells took residence in the bone marrow.

The new immune system would no longer attack tissues of the body in the person with autoimmune disease. For example, eliminating the cause of the disease in people with a genetic disorder such as sickle cell anemia, the new blood system would not have the sickle-cell mutation. But the hurdles that stand in the way are tall.

First, the researchers don’t know whether the same molecule on human blood-forming stem cells would be the right one to target with a therapy. Additionally, a functioning immune system is missing in the mice involved in the study. Before tests can begin on humans, the technique must first be tested on mice with normal immune systems.

Weissman said he considered this work to be the beginning of research that could lead to human studies although the steps will take time to overcome.

The November 23rd issue of Science published the study.

Also contributing to the work was postdoctoral scholar, Daniel Kraft, MD.

The National Institutes of Health, the Cancer Research Institute, and the Stanford Medical Scholars Program provided fellowships to fund the research.