Routing gene therapy directly into brain

Researchers from Boston Children's Cancer and Blood Disorders Center have found a revolutionary way to transplant hematopoietic stem cells (HSCs) directly to a patient's brain. Traditionally, HSCs were thought to be transplanted only through an intravenous line into the bloodstream. This is problematic because the stem cells must mature and naturally circulate into the brain, which can be a slow process. In a mouse model, Dr. Alessandra Biffi of Boston Children's Hospital and her team found a way to deliver stem cells directly to the brain in a mouse model. The study involved treatment of mice that had a lysosomal storage disorder, which is enzyme imbalance that leads to a dangerous buildup of lipids, carbohydrates, and other materials that severely impacts the central nervous system. The researchers used the mice to transplant the HSCs directly to the ventricles of the brain and termed the method intracerebroventricular delivery. This approach enabled the stem cells to release signaling cytokines that counteract neuroinflammation caused by the lysosomal storage disorder. They found that the transplanted HSCs had not migrated to other parts of the central nervous system, which showed potential to create a chimera, a separate genetic profile within an organism. Researchers implicated that this capability to create chimeras within the brain could further treat neurodegenerative diseases such as Parkinson's, Alzheimer's, and ALS.
This innovative discovery has taken stem cell therapy to another level by optimizing its approach to be more effective. Direct delivery to the central nervous system is known to have a prompt sequelae. This could treat devastating and time sensitive diseases of the brain such as Huntington's disease and malignant brain tumors. The novel approach of intracerebroventricular delivery advances stem cell therapy and opens new windows for treating an array of medical conditions that affect the brain.
https://www.sciencedaily.com/releases/2017/12/171206174240.htm
http://advances.sciencemag.org/content/3/12/e1701211

Hidden Genetic Mutations in Stem Cells Could Weaken Therapeutic Benefit

A microscopic image of human induced pluripotent stem cells (iPS). 

Mutations in mitochondrial DNA occur more frequently in individual cells as the human body ages. Since there are thousands of mitochondrial mutations and most of them are hidden, researchers have a hard time identifying all of the mutations present in a sample of a blood or piece of skin. However, researchers are able to distinguish the mutations easier if they are in iPS cells. In order to identify these mutations, iPS cells undergo a process where they are cloned in skin or blood cells which results in a iPS cell line that contains the same mitochondrial DNA mutations as the original adult cell. 

In a study conducted by Shoukhrat Mitalipov, director of the Center for Embryonic Cell and Gene Therapy at Oregon Health and Science University, researchers analyzed mitochondrial DNA mutations in 20 iPS cloned cell lines per patient that were obtained from blood and skin samples from healthy people and people suffering from degenerative diseases. When the iPS cell lines were sequenced, the researchers discovered that there was a significantly high number of mitochondrial mutations in the cells of patients who were over 60 years old. Based off of the results, the researchers observed that the larger the number of mutations in mitochondrial DNA caused a greater compromise to be made in the cells functions. Additionally, any defects in the mitochondria can potentially weaken or diminish the iPS cells ability to repair damaged tissues and organs. From this study the team of researchers discovered that iPS cells, specifically a type of stem cell from blood or skin sample, contain mutated mitochondrial DNA. In order to effectively use iPS cells to their full potential in humans, medical geneticist Taosheng Huang suggests that doctors and researchers need to check first if there are any mutations in the mitochondrial genome (Oregon Health and Science University 2016). 

I think that potential therapies involving the use of iPS stem cells can be used to treat diseases that occur with old- age. In the article, Mitalipov expressed that "pathogenic mutations in our mitochondrial DNA have long been thought to be a driving force in aging and age- onset diseases, though clear evidence was missing. Now with that evidence at hand, we know that we must screen stem cells for mutations or collect them at a younger age to ensure their mitochondrial genes are healthy" (Oregon Health and Science University 2016). In my opinion, I think the background knowledge of how cells are damaged with old age can serve as a basis for future studies to further examine how mutations in the mitochondria play a role in degenerative diseases. 

Embryonic Stem Cell Therapy Reports of Long-Term Safety to Treat Human Disease

The Lancet recently published new research in which the first evidence of "medium-term to long-term safety and tolerability of transplanting human embryonic stem cells (hESCs) in humans has been revealed by scientists." The study was conducted on 18 patients who had severe vision loss. They received hESCs and appear to be safe 3 years post-transplant. More than half of the patients experienced restoration of some sight.

"Embryonic stem cells have the potential to become any cell type in the body, but transplantation has been complicated by problems including the risk of teratoma formation and immune rejection," Professor Robert Lanza, Chief Scientific officer at Advanced Cell Technology in the USA. "As a result, immunoprivileged sites (that do not produce a strong immune response) such as the eye have become the first parts of the human body to benefit from this technology."

The participants had one of two different types of eye disorders, half having Stargardt's macular dystrophy and the other half having dry atrophic age-related macular degeneration. Both of these conditions have no effective treatment and they can both lead to complete blindness. The hESCs were differentiated into retinal pigment epithelium cells and were injected in different doses. Some patients received 50,000 retinal cells, some 100,000, and some 150,000 cells. These cells were placed into the space under the retina of the eye (the area with the worse vision).

The hESC cells were accepted and tolerated for "up to 37 months after transplantation." If the patients experienced any adverse effects, after close analysis, it is safe to say that they were not caused by the hESCs. Additionally, 10 of the 18 patients claim to have had significant improvement in their vision in the eyes that received the stem cell treatment.

"Our results suggest the safety and promise of hESCs to alter progressive vision loss in people with degenerative diseases and mark an exciting step towards using [these] stem cells as a safe source of cells for the treatment of various medical disorders requiring tissue repair or replacement," co-lead author Dr. Steven Schwartz, Jules Stein Eye Institute.

Dr. Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine, states how this study is a "major accomplishment" but also that "much work remains to be done before hESC and induced pluripotent stem cell therapies go beyond regulatory trials, but the path is now set in motion."

I absolutely loved this article because I have always had great interest in stem cell therapy. This is a huge step forward for the practice and potential use of hESCs as common treatments for certain disorders or anything else requiring the repair or replacement of tissues. I'm very excited for what is upcoming in the medical field because of advancements such as this in the area of stem cell research and therapy.

Article: http://www.sciencedaily.com/releases/2014/10/141014211709.htm 
Related Article: http://health.usnews.com/health-news/articles/2014/10/14/embryonic-stem-cell-therapy-shows-long-term-effectiveness-safety