41 posts categorized "Patient information"

July 28, 2011

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May 31, 2011

iPSCs: A tool for understanding ‘A Beautiful Mind’?

By Angela C. H. McDonald

A young brilliant mathematician seen by his colleagues as agitated, socially withdrawn, emotionally flat and paranoid is approached by a Department of Defense agent who requests his assistance with code breaking. Following acceptance of this job, the young professor believes he is being followed and is eventually chased through his university campus, captured and sedated. When the young professor comes to, he is in a psychiatric hospital and forced to realize that his secret work for the Department of Defense is one of his schizophrenic delusions. This is the story of John Nash portrayed in the film A Beautiful Mind. Like many individuals suffering from schizophrenia (1 in every 100 Canadians), John Nash struggles throughout his life with an array of symptoms including delusions and hallucinations. 

Can induced pluripotent stem cells (iPSCs) help us understand the underlying mechanism of this devastating and complex condition?  Maybe.

Scientists have proposed the use of iPSCs for modeling human disease however; many question the usefulness of iPSCs for modeling complex neurological diseases such as schizophrenia. Last month a team of researchers led by Fred Gage at the Salk Institute published in Nature the first example of modeling a complex neurological disease in a dish.

Skin fibroblasts from schizophrenia patients were obtained from a cell bank and reprogrammed into iPSCs. Patient-derived iPSCs were differentiated into neurons to study the cellular and molecular mechanisms of schizophrenia. The researchers found that patient-derived neurons were electrophysiologically equivalent to control neurons and the levels of a number of synaptic maturation markers were unaffected. However, schizophrenia neurons did show a decrease in the number or neuronal projections, decreased neuronal connectivity and alterations in global gene expression. Over 550 genes were aberrantly expressed in schizophrenia neurons, 25 per cent of which have been previously linked to the disease.

iPSC-derived schizophrenia neurons were treated with five antipsychotic drugs in an attempt to improve neuronal connectivity in vitro. The drugs were administered for the final three weeks of neuronal differentiation. Loxapine, an antipsychotic commonly used to treat schizophrenia was the only antipsychotic drug that significantly increased neuronal connectivity in all patient iPSC derived-neurons.

Interestingly, this is not the first study to investigate the molecular mechanisms of schizophrenia in vitro. A small number of studies have been performed on cultured fibroblasts from skin biopsies of schizophrenia patients. One study identified a cell proliferation defect in patient fibroblasts. While studying patient fibroblasts may provide some insight into disease mechanisms many scientists stress the importance of studying the appropriate cell type in vitro. For example, in the Nature paper noted above, Fred Gage’s group reported increased NRG1 (a protein thought to be involved in schizophrenia) expression in schizophrenia neurons but not SCZD fibroblasts, which they suggest, demonstrates the importance of studying the relevant cell type.  

I recently attended a Stem Cell Journal Club session at the Hospital for Sick Children where this paper was presented. Stem cell and neurobiologists in attendance raised a number of concerns about this study includingthe difficulty of modeling a complex systems disease that is thought to be a dynamic process, leading to the dysfunction of many pathways in the brain. How much insight will researchers have into this disease if they are studying only a few types of neurons in a dish? Even though many scientists are skeptical, we can’t disregard that almost all insight into the molecular mechanism of schizophrenia in human patients has come from the study of postmortem brain tissue. iPSCs are the only source of live human neurons available to researchersfor studying this devastating disease and for this reason, scientists should continue to use and optimize neurons from iPSCs.


May 05, 2011

Researchers hit the bull's EYE

By Angela C.H. McDonald

Generating complex organ tissue from pluripotent stem cells is a major challenge in the field of regenerative medicine. Significant progress has been made in directing pluripotent stem cells to differentiate into specific cell types however; there have been few examples of the successful production of organ tissue in vitro. Last month, a group of researchers from Japan reported in Nature the remarkable generation of optic cup tissue from mouse embryonic stem cells in a dish.

NatureApril2011 Following 8-10 days of culture in defined retinal inducing conditions and in the presence of extracellular matrix proteins, embryonic stem cells differentiated to form three-dimensional structures that molecularly and morphologically resemble optic cup tissue in vivo. Using an embryonic stem cell line containing a fluorescent reporter gene expressed in the developing eye, researchers captured the elegant morphogenetic process of optic cup formation in a dish using live imaging. Stunning videos demonstrate the outpouching of embryonic stem cell aggregates and their subsequent morphological movements that result in an optic cup, recapitulating mammalian eye development. 

This new tool has developmental biologists excited about the possibility of elucidating molecular interactions that orchestrate eye development as well as the possibility of isolating stage-specific progenitor cells throughout optic cup development. 

But what does this research mean for patients suffering from degenerative eye disease?  The authors anticipate that application of this technology to human pluripotent stem cell lines could open up the possibility of generating artificial retinal tissue sheets for transplantation. 

Many eye diseases including age-related macular degeneration result from degeneration of retinal tissue. Following disease or injury, the human retina does not regenerate, leaving an individual with impaired vision. For patients suffering from degenerative eye disease, tissue transplantation is the only hope for regaining lost sight.  

There is reason to be optimistic about the potential of embryonic stem cell-derived retinal cells to treat eye disease. In fact, a number of groups around the world are working to move their stem cell technologies forward into clinical trials. However, stem cell therapy holds an array of challenges including the ability to coax transplanted cells into forming complex functional tissue layers. 

In April, Chinese and American researchers published their results following the transplantation of rod photoreceptors derived from swine induced pluripotent stem cells into swine retina in the journal Stem Cells. While the survival of a small number of injected cells and their subsequent differentiation into a mature morphology is exciting, there was no functional improvement in electrophysiological response to light. In contrast, transplantation of fetal retinal tissue into human patients can restore some visual acuity however ethical and supply issues hamper the use of fetal transplants as a viable therapeutic option. Optic cup tissue generated from pluripotent stem cells in vitro is an intriguing alternative.

While the generation of optic cup tissue in a dish from mouse embryonic stem cells is exciting, much more work needs to be done before we can think about therapeutic applications, beginning with the transfer of this technology to human pluripotent stem cells.

Why should regenerative medicine efforts focus in part on eye regeneration? Well for starters, one million Canadians have some form of age-related macular degeneration. According to the Canadian National Institute for the Blind, more Canadians have age-related macular degeneration than breast cancer, prostate cancer, Parkinson’s or Alzheimer’s disease combined. The economic impact of eye disease is staggering -– the National Coalition for Vision Health reports the cost of vision loss in 2007 as $15.8 billion, which includes direct health care costs as well as the indirect costs of lost productivity, welfare and other expenses. By 2032, this figure is expected to double, making a need for therapies even more pressing.   


May 04, 2011

Controversial stem cell clinic closed

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April 12, 2011

Reconstructing tissues using fat stem cells and the thin line between clinical and cosmetic needs

by Michelle Ly

Reconstructive surgery plays an important role in recovery from disease and injury by attempting to restore function or appearance to the body. While the use of synthetic materials is commonplace, the ability to replace or reconstruct using the same tissues from elsewhere in the body is desirable because it would eliminate many issues that occur with synthetic materials, such as higher infection rates and foreign body reactions.   

One new technique being investigated in the field of reconstructive medicine uses an adherent, multipotent population of cells called adipose-derived stem cells (ASCs). ASCs are isolated from subcutaneous body fat by taking minced tissue fragments, digesting it with an enzyme called collagenase, and then spinning out the resultant mixture to separate the stem cell containing layer. As a type of stem cell, ASCs can theoretically differentiate into any of the adipose cell lineages, making them an extremely useful tool in regenerative medicine. However, the extent of differentiation in ASCs has been questioned, especially in comparison to standards set by other stem cell populations. 

While the supporting technologies in this emerging field are still undergoing development and refinement, some clinical progress has already been achieved. California-based Cytori Therapeutics reported success with a clinical trial to reconstruct breast tissue following breast cancer surgery using what they call “adipose-derived stem and regenerative cells” (ADRCs). The study was conducted across several European health centers and was led by co-principal investigators Dr. Weiler-Mithoff and Dr. Rosa Pérez Cano at the Hospital Universitario Gregorio Marañón in Madrid, Spain. The procedure takes fat from the patient by liposuction and then harvests and processes the ADRCs for inclusion in “cell enriched fat grafts” which are used to reconstruct the breast.

These early successes have not been achieved without criticism however, and some researchers are urging caution in patients and researchers interested in ASC based therapies. In addition to questions about the level of cell differentiation, a recent review pointed to unresolved issues in large-scale engineering and differences in stem cell purity depending on tissue source. Other researchers warn that some studies do not adequately account for the heterogeneity of the ASC population and how that may affect clinical treatments.

With the growing attention to stem cell procedures in recent years and the accompanying rise of marketed stem cell treatments, both clinical and cosmetic, it is more important than ever for patients and their doctors to focus on well-researched studies and trials. As such, future studies in ASC-based treatments will need to address concerns about isolation, purification and differentiation in order to continue with progress in academia and industry.

April 05, 2011

Using stem cells in developmental disorder research

Every two hours, someone is born with Rett Syndrome (RTT), a developmental disorder seen almost always in girls, but occasionally in boys. Those with the disease usually develop normally until they reach 12-18 months, at which point development stops and oftentimes is reversed, causing previously developed skills to deteriorate.

RTT is typically placed under the autism spectrum of disorders (although some have questioned this classification), and is the only autism-spectrum disorder with a known cause: A mutation in the MECP2 gene located on the X chromosome. With the cause known, researchers have a ‘starting point’ to look at for possible ways to combat the disorder, and that’s exactly what they’ve done.

One well-known researcher in the field is Dr. In-Hyun Park from the Yale Stem Cell Center, who presented his work at the Ottawa Hospital Research Institute’s Sprott Centre for Stem Cell Research in late March.

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March 24, 2011

Tiny zebrafish shows how kidney regeneration could be achieved

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February 14, 2011

It’s a matter of attraction: homing and mobility in the blood system

by Michelle Ly

Cancer Hearts You, by Craig Aarts In previous posts, I discussed the use of cell therapy, specifically the application of allogenic or autologous hematopoietic stem cells (HSCs), as a way to repopulate blood cell lineages to normal levels post-treatment in patients suffering from certain types of blood-related cancers. These therapies would not be successful if not for the ability of stem cells to home and migrate. All cell therapies rely on the cells to somehow find their way through the body, migrate to the appropriate stem cell niche, and from there, differentiate and repopulate the target system. This process was discussed by Tsvee Lapidot at the recent Annual Meeting for the American Society of Hematology.

During his seminar, Dr. Lapidot discussed the dynamic nature of stem cell niches, the environment in which stem cells are found and regulated. The hematopoietic stem cell niche is found in the bone marrow and formed by a variety of cell types, including stromal cells. Bone marrow stromal cells can maintain HSCs in a quiescent inactive state indefinitely. But sometimes the body needs to replenish its cells, requiring that stem cells be allowed to differentiate and migrate. This suggests that stem cell niches are changeable and one mechanism for this change is through the regulation of a protein called “stromal cell-derived factor-1” (SDF-1).

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January 27, 2011

Progress being made in developing stem cell-based treatments for ALS/MND

Earlier this week, many of the world’s leading scientists engaged in developing stem cell-based treatments for Amyotrophic Lateral Sclerosis (ALS) or Motor Neuron Disease (MND) met for the first time as a group to share their work. Held in New York, the meeting was organized by the International Consortium of Stem Cell Networks in partnership with the ALS Association and the Motor Neuron Disease Association. Researchers, physicians, surgeons and patient advocates from more than a dozen countries participated.

At present, there is no consensus on the etiology (i.e. the cause or origin) of ALS, and there is a recognition that the disease presents in many forms. Furthermore, while it is often thought of as a single disease, there is ongoing debate about whether it is a disease or a syndrome (a range of conditions). To patients, it doesn’t really matter:  today, diagnosis is a death sentence within three to five years, as the body slowly and painfully shuts down. But for science, this distinction is important, because understanding the cause will allow treatments that target the cause, rather than relieve the symptoms, to be developed.

Nevertheless, progress is being made. While differences abound on the cause of the disease there is more consensus to how stem cells can help to find the answer. The discovery of iPS cells has revolutionized the process of scientific discovery in this field. Many of the world’s leading ALS labs have formed an iPS consortium funded by the US National Institutes of Health, ALS Association and others to develop new stem cell lines from patients living with ALS. These lines are being used in two different ways: 

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January 12, 2011

Stem cells in a bottle

In an article in the Globe and Mail this past weekend, reporter Carolyn Abraham provided an interesting and under-reported glimpse into the cosmetics industry use of stem cells to market their products. She notes:

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