Katie Pratt, PhD – Brain Blogger http://brainblogger.com Health and Science Blog Covering Brain Topics Wed, 30 May 2018 15:00:03 +0000 en-US hourly 1 https://wordpress.org/?v=4.9.6 Cord Blood-Derived Stem Cells – a New Therapeutic Option for Brain Disorders? http://brainblogger.com/2012/09/20/cord-blood-derived-stem-cells-a-new-therapeutic-option-for-brain-disorders/ http://brainblogger.com/2012/09/20/cord-blood-derived-stem-cells-a-new-therapeutic-option-for-brain-disorders/#comments Thu, 20 Sep 2012 11:00:52 +0000 http://brainblogger.com/?p=13180 Stem cell technology has the potential to revolutionize medicine, but the revolution has been considerably slower than expected. Government restrictions and ethical dilemmas have put up roadblocks to fast-paced biological research, and even when these roadblocks are absent, controlling the behavior of stem cells (cells that have the ability to form a number of cell types and tissues) in a petri dish has proved tricky to say the least.

In one particular area of stem cell research, however, progress has been steady. Cord blood stem cells can be harvested from the umbilical cord and placenta of a newborn baby and stored for future use, the idea being that they can be used down the road should that baby (or a genetically similar relative) become sick. These stem cells have been used to treat close to 100 blood-based conditions, including several types of leukemia.

One particular challenge has been to force cord blood stem cells to become anything other than a blood cell. This is because stem cells exist in varying degrees of “stemness”; that is they differ in their ability to form different kinds of tissue or cells. For example, blood stem cells are really good at generating all of the different types of blood cells, but do not generate skin cells. However, researchers at the Salk Institute for Biological Studies in collaboration with scientists in Barcelona, Spain, have succeeded in coaxing these stem cells to become neurons, a groundbreaking step in the treatment of traumatic brain injury and other neuronal disorders.

When a stem cell divides, the DNA of one cell retains its stem cell identity. The DNA in the second cell, on the other hand, can assume a different identity. The first step in assuming this identity (known as differentiation) generally involves turning on a master-regulator gene that then controls the activity of another gene and another gene and so on until, for example, the cell becomes a neuron. The key to controlling stem cells, therefore, lies in figuring out how to turn on the master-regulator.

In order to turn cord blood cells into neuronal cells, Alessandra Giorgetti and colleagues first manipulated the cells so that they produced an increased amount of a gene called Sox2. They then cultured the cells and analyzed their genetic behavior. What they found was that these manipulated cells were starting to behave like immature neurons: Sox2 was the master-regulator.

The next challenge was to keep the cells on track so that they finished the job of becoming a neuron. Using special conditions the team managed to get the cells to form mature neurons that both extended long nerve-like projections and responded to electrical stimulation in vitro.

The real test, however, was whether or not these cells repopulate a damaged brain. It is one thing to generate a single cell type, and quite another to induce those cells to form a coherent and functional tissue. Giorgetti and her colleagues therefore took the cord blood-derived neuronal cells and transplanted them into immuno-compromised mice (that could not reject the non-mouse graft) and monitored their progress over a period of three months. They found that indeed the cord blood-derived neurons grew and integrated into the mouse brains, and were capable of limited activity.

While it maybe some time before such a treatment reaches the clinic, this work emphasizes the potential of this type of stem cell. With cord blood banking becoming more and more commonplace, and an expansion of the application of cord blood stem cells beyond the treatment of blood disorders, these malleable cells are fast becoming the stars of stem cell research.


Alessandra Giorgettia, Maria C. N. Marchettob, Mo Lic, Diana Yub, Raffaella Fazzinaa, Yangling Mub, Antonio Adamoa, Ida Paramonova, Julio Castaño Cardosoa, Montserrat Barragan Monasterioa, Cedric Bardyb, Riccardo Cassiani-Ingonia, Guang-Hui Liuc, Fred H. Gageb, & Juan Carlos Izpisua Belmontea (0). Cord blood-derived neuronal cells by ectopic expression of Sox2 and c-Myc PNAS DOI: 10.1073/pnas.1209523109

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Vaccine for Parkinson’s Disease Enters Phase 1 Clinical Trial http://brainblogger.com/2012/09/14/vaccine-for-parkinsons-disease-enters-phase-1-clinical-trial/ http://brainblogger.com/2012/09/14/vaccine-for-parkinsons-disease-enters-phase-1-clinical-trial/#comments Fri, 14 Sep 2012 11:00:21 +0000 http://brainblogger.com/?p=13118 The word “vaccination” generally brings to mind the prevention of infectious disease. However, significant advances have recently been made in the field of therapeutic vaccination for the treatment of chronic human disorders including neurological conditions and cancer.

Simply put, a vaccine is a mixture of compounds (most often proteins) that are selected for their ability to activate the immune system. These compounds, also known as antigens, are then injected into the body where they prepare the immune system for a future assault. The result of such prophylactic vaccination is either complete immunity to the illness, or at least a significant reduction in disease severity.

While a prophylactic vaccine is administered as a preventative measure, therapeutic vaccines are intended to help fight a disease that has already taken root. For example, a therapeutic vaccine might be given to a patient with cancer in order to enlist the patient’s own immune system in the fight against the disease.

The problem with this kind of approach is ensuring that the antigen used in the vaccine does not induce an immune response against healthy parts of the body. Again, using cancer as an example, diseased cells often contain mutated proteins, or proteins that are not usually expressed in adult tissue (known as onco-fetal genes). This means that vaccines using these antigens specifically target cancer cells.

Recently, a therapeutic vaccine for Parkinson’s disease developed by Austrian pharmaceutical company Affiris entered a clinical trial, a landmark move in the management of a disease that is currently only treated at a symptomatic level.

Patients with Parkinson’s disease suffer from a number of debilitating symptoms that are the result of the loss of a particular class of neurons in the brain. These neurons are involved in the control of muscle function and are particularly sensitive to the neurotransmitter dopamine. It is for this reason that current treatments revolve around modulation of the levels of this chemical.

The underlying molecular cause of the disease is a protein called alpha-synuclein. Ordinarily this protein is found throughout the neocortex, hippocampus, thalamus, substantia nigra, and cerebellum, although its precise function remains unknown. Importantly, this protein is very unusual in that it does not fold up like the majority of proteins. Its “floppy”, unfolded appearance means that it is particularly susceptible to getting tangled up and forming protein aggregates within brain cells, thus sentencing the affected cell to death. The formation of protein aggregates also underlies other brain disorders, including Alzheimer’s disease and Creutzfeld-Jacob disease.

It is the alpha-synuclein protein tangles that are targeted by the vaccine currently in trials, PD01A. The study, funded by the Michael J. Fox Foundation to the tune of $1.5 million, will assess the safety of the vaccine in both men and women with Parkinson’s disease, with the results expected in July of 2014.

Given the prevalence of protein aggregates in brain diseases, therapeutic vaccination might therefore represent a promising future treatment for several neurological conditions.

Image via Alexander Raths / Shutterstock.

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New Hope for Alzheimer’s Treatment – iPS Cells to the Rescue? http://brainblogger.com/2012/08/10/new-hope-for-alzheimers-treatment-ips-cells-to-the-rescue/ http://brainblogger.com/2012/08/10/new-hope-for-alzheimers-treatment-ips-cells-to-the-rescue/#comments Fri, 10 Aug 2012 11:00:27 +0000 http://brainblogger.com/?p=12983 Over 5 million Americans are living with this heritable form of dementia for which there is no cure. Caring for patients with Alzheimer’s disease is estimated to cost over $200 billion dollars annually, not to mention the untold costs to family members and care givers. This year’s Alzheimer’s Association International Conference out of Vancouver offered advances in experimental systems, diagnostics, and treatments.

One particularly striking report is that Scott Noggle’s group from the New York Stem Cell Foundation (NYSCF) have succeeded in culturing skin cells from Alzheimer’s patients and inducing them to form brain cells. Alzheimer’s disease is a progressive condition in which certain cells of the brain called cholinergic basal forebrain neurons start to die. The precise cause of this is unknown, and, given the differences between patient symptoms, there are likely multiple underlying pathologies.

Noggle and his colleagues took advantage of new advances in stem cell technology to try to understand how Alzheimer’s disease manifests. First, they took skin cells from 12 patients with early-onset Alzheimer’s disease and induced these cells to form pluripotent stem cells, or iPS cells. iPS cells have the ability, given the right chemical cues, to form any cell of the body. The scientists then coaxed these iPS cells to form cholinergic basal forebrain cells, the cells that are affected in the disease.

The fact that cells were taken from 12 patients and several healthy individuals means that Noggle’s team can now look for genetic and physiological defects that might cause the confusion, aggressive behaviors, and long-term memory loss that are indicitive of Alzheimer’s disease. Knowing how each of the 12 patients progressed will allow the scientists to link symptoms with physiological changes at the cellular level. This is a ground-breaking move, as until know studying brain cells from patients was impossible.

Not only do these cells represent an invaluable research tool, “Patient derived AD cells will prove invaluable for future research advances,” said NYSCF CEO Susan Solomon. “They will be a critical tool in the drug discovery process, as potential drugs could be tested directly on these cells.” She also pointed out that this work will reduce the number of drug tests performed on laboratory animals such as mice and rats.

Perhaps the most exciting downstream consequence of this work will be to understand the global changes that lead to neuron loss, and, with such information, the lives of many millions of people living with dementia can be changed for the better.


NYSCF. New York Stem Cell Foundation scientists featured at the Alzheimer’s Association International Conference for new model of Alzheimer’s disease (AD). July 16, 2012.

Image via Filipchuk Oleg Vasiliovich / Shutterstock.

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