Stem Cell Research

Blood-Brain Barrier Building Blocks Generated From Human Stem Cells

The blood-brain barrier -- the filter that governs what can and cannot come into contact with the mammalian brain -- is a marvel of nature. It effectively separates circulating blood from the fluid that bathes the brain, and it keeps out bacteria, viruses and other agents that could damage it.

However, the barrier can be disrupted by disease, stroke and multiple sclerosis, for example, and also is a big challenge for medicine, as it can be difficult or impossible to get therapeutic molecules through the barrier to treat neurological disorders.

Now researchers have transformed stem cells into endothelial cells with blood-brain barrier qualities in a laboratory dish in an attempt to get the blood-brain barrier to share its secrets.

“The nice thing about deriving endothelial cells from induced pluripotent stem cells is that you can make disease-specific models of brain tissue that incorporate the blood-brain barrier,” explains Sean Palecek, a UW-Madison professor of chemical and biological engineering. “The cells you create will carry the genetic information of the condition you want to study.”

Precision At Choosing Stem Cells A Step Forward For Treating Multiple Sclerosis, Other Diseases

Researchers have improved efforts to pluck out just the right stem cells to address the brain problem at the core of multiple sclerosis and a large number of rare, fatal children’s diseases.

New research has isolated and directed stem cells from the human brain to become oligodendrocytes, the type of brain cell that makes myelin, a crucial fatty material that coats neurons and allows them to signal effectively.

Researchers injected the chosen cells into the brains of mice that were born without the ability to make myelin. Twelve weeks later, the cells had become oligodendrocytes and had coated more than 40 percent of the brain’s neurons with myelin – a four-fold improvement over previous results.

Mesenchymal Stem Cells Enter Phase I Trial For Multiple Sclerosis

Stem cell therapies involving mesenchymal stem cells have so far created by far the most market capitalization of any therapeutic vector focused on by publicly traded stem cell sector companies.

In MS, the immune system attacks the myelin and the exposed nerves’ intricate wiring can be damaged. The result: nerve signals can be blocked, causing loss of balance and coordination, cognitive ability and other functions. Losses may become permanent.

Now three prestigious U.S. institutions are combining efforts in an attempt to find out whether mesenchymal stem cells (MSCs) and growth factors can cure or assist in the cure of Multiple Sclerosis.

Bone Marrow Stem Cells Show Therapeutic Promise In Multiple Sclerosis

Bone marrow stem cells have been shown in several experimental studies to have beneficial effects in disease models of MS.  Now, in a groundbreaking trial, bone marrow stem cell therapy has been shown to have possible benefits for the treatment of the disease in a small group of patients with multiple sclerosis (MS). 

The study explored the safety and feasibility of cell therapy in patients with MS.  Participants had a general anaesthetic during which bone marrow was harvested.  The marrow cells were filtered and prepared so that they could be injected into the patient’s vein later the same day.

The procedure was well tolerated and the participants were followed for a year.  No serious adverse effects were encountered.  The results of clinical scores were consistent with stable disease.  The results of neurophysiological tests raised the possibility of benefit.

Professor Neil Scolding said: “We are encouraged by the results of this early study.  The safety data are reassuring and the suggestion of benefit tantalising.  A larger study is required to assess the effectiveness of bone marrow cellular therapy in treating MS.  We are hopeful that recruitment to this phase 2/3 study may begin towards the end of this year.

“Research into the underlying mechanisms is ongoing and vital, in order to build on these results.  We believe that stem cells mobilized from the marrow to the blood are responsible, and that they help improve disease in several ways, including neuro-protection and immune modulation.”

The aim of the trial was to find out what effects, good or bad, bone marrow stem cells has on patients with MS, and their disability.

Bone marrow is known to contain stem cells capable of replacing cells in many types of tissues and organs - and so is of great interest to those working to develop new treatments for many diseases, including those affecting the nervous system.

See also the June 2009 Northwestern University study.

Adapted from the University of Bristol announcement.

Novartis Buys Opexa's Multiple Sclerosis, T-cell Immunotherapy For $50 Million

Big pharma is increasingly stepping up to the stem cell line.  In November 2008, Osiris Therapeutics announced a strategic alliance with Genzyme for the development and commercialization of certain Osiris stem cell products. Osiris is to commercialize Prochymal and Chondrogen in the United States and Canada, and Genzyme will commercialize the treatments in all other countries. Under the terms of the agreement, Genzyme will make a $130 million up-front payment to Osiris, with $75 million paid initially and $55 million to be paid on July 1, 2009. In addition, Osiris also has the potential to receive a total of up to $1.25 billion in milestone payments from Genzyme.

The Novartis/Opexa Deal:

Now Novartis and Opexa Therapeutics have announced a product research and development sale that could bring Opexa $50 million.  The announcement was made early in the market day and Opexa closed with a market capitalization of $24.6 million having traded up from $.47 to $2.01 during the day. Under the terms of the agreement, Novartis will acquire the technology described below from Opexa. Novartis will have full responsibility for funding and carrying out all research, development and commercialization activities. Opexa will receive an upfront cash payment of $3 million, plus an additional $1 million as a technology transfer fee to be paid over the course of a six month period. Total payments to Opexa, including the upfront payment, the technology transfer fee and development and commercial milestone payments could exceed $50 million not including royalties.

What Novartis is buying:

New Cedars-Sinai Regenerative Medicine Institute to Emphasize Induced Pluripotent Research

The Cedars Institute will be housed in new state-of-the-art laboratories being constructed especially for stem cell and regenerative medicine research. At the heart of the Institute will be a specialized core facility for the production of Induced pluripotent stem cells.

Clive N. Svendsen, Jamie Thomson associate and joint leader of the widely-respected Stem Cell and Regenerative Medicine Center at the University of Wisconsin, has been named to lead the new unit.  He has quite a resume; one that includes professor of neurology and anatomy at the University of Wisconsin-Madison, and consulting professor at Stanford University. Svendsen’s research focuses on both modeling and treating neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) and Parkinson’s disease using a combination of stem cells and growth factors.

Multiple Sclerosis: Stem Cell Advances Toward A Cure

Multiple sclerosis symptoms have been reversed in early stage patients by using bone marrow stem cell transplants to reset the immune system.

Some 81 percent of patients in the early phase study showed signs of improvement with the treatment, which used chemotherapy to destroy the immune system, and injections of the patient's bone marrow cells taken beforehand to rebuild it.

Northwestern University Stem Cell Transplant Reverses Early-Stage Multiple Sclerosis

We try to address only those research findings that seem to be repeatable breakthroughs or more basic advances that may result in repeatable therapeutic breakthroughs down the line. Recently, Universitatsmedizin Berlin in Germany reported a 42-year-old HIV patient with leukemia free of detectable HIV in his blood, and with no HIV symptoms, after a stem cell transplant from a donor carrying a gene mutation that confers natural resistance to the virus that causes AIDS. This HIV free state is holding two years after treatment for the leukemia that included the donor gene mutation.

While published in the New England Journal of Medicine, we did not report it here only because of the time and difficulty of repeating the procedure in a controlled study.  The danger of such transplants and the possibility the virus may be 'hiding' elsewhere in the 42 year old's body also preclude getting overly excited at this point.  That said, it is a fascinating demonstration of our increasing knowledge of genetic manipulation. 

On the other hand, doctors at Northwestern University found success by injecting multiple sclerosis patients with their own immune stem cells taken from them before chemotherapy.  This is normal procedure in stem cell transplants in order to have the stem cells available to create a new immune system after the old one has been destroyed.

Multiple Sclerosis: Single Gene Found To Redirect Differentiation Of Nueral Progenitor Cells

A recent Stem Cell Digest post reported researchers at the Burnham Institute in San Diego had for the first time genetically programmed embryonic stem cells to become nueral cells when transplanted into the brain.

Now, researchers at the Salk Institute for Biological Studies have directed mouse neural progenitor cells (stem cells partially differentiated into nueral cells) to differentiate into support (glial) cells instead of continuing toward becoming neural cells.  They have done so in vivo and by introducing only one gene, Ascl1.

Multiple Sclerosis: Bone Marrow Stem Cell Transplant Effective In Stopping MS?

Various blood cancers have been treated by destroying a patients immune system with chemotherapy and then creating a new immune system through bone marrow stem cell transplant. This is the oldest use of stem cell regenerative medicine and is very well established.

Way back in 2000, Doctors at the Ottawa Health Research Institute got an idea.  It seems that Multiple Sclerosis symptoms in patients unfortunate enough to contract leukemia on top of their MS were observed to improve after going through the bone marrow transplant procedure.  Dr. Mark Freedman, neurologist and bone marrow transplant physician Dr. Harold Atkins, both of OHRI, decided to try and experiment.  Because the transplant process is difficult, requiring the complete destruction of a patient's immune system prior to fresh stem cell introduction, the study was designed for patients with rapidly progressing MS who were headed for severe disability.