Embryonic Stem Cell Differentiation

Within the inner cell mass of an embryo are three distinct regions of stem cells including the cells which form the outermost layer. These cells go on to form the various cells of the nervous system, skin, sensory organs, and similar body structures, and are known as the ectoderm. Those cells in the center of the inner cell mass are known as the mesoderm and form other tissues such as the internal organs like the liver, and kidneys, along with muscle, connective tissue, and bone. The endoderm is the origin of the gastrointestinal tract and the lungs and relies on the mesodern to connect its structures to the ectoderm. These three layers of stem cells within the embryo together form the more than 200 different cell types within the human adult body. They are termed pluripotent, but are not totipotent as they cannot form the extraembryonic cells necessary for placental development or membranes formed in pregnancy.

Human embryonic stem cells rely on the presence of a number of transcription factors in order to remain pluripotent and prevent differentiation through gene signalling. These transcription factors, such as Oct-4, Nanog, and Sox2 are being investigated for their potential to influence the plasticity of adult stem cells, making these multipotent stem cells more like pluripotent embryonic stem cells.

Embryonic Stem Cell Differentiation

The variability of embryonic stem cells to differentiate into any cell type has both advantages and disadvantages for therapeutic applications and research. Whilst there is an increase in scope of treating numerous diseases of many organs and tissues, the importance of controlling how the embryonic stem cells differentiate has been highlighted by individual cases where unwanted tissues have formed following the implantation of hESCs. There have been reports of patients who underwent embryonic stem cell transplants for Parkinson’s Disease and other neurological conditions and who have subsequently developed bone, hair, and rapidly-expanding tumors in the areas of the brain receiving the transplant. Uncontrolled and unregulated use of embryonic stem cells in clinics overseas presents a significant danger to patients who are unable to access treatment in the US, especially when the stem cells are injected directly into the brain by unqualified or inexperienced clinic staff.

Embryonic Stem Cell Research

Embryonic stem cell research has led to the development of therapeutic cloning, a practice whereby an enucleated egg is combined with the somatic cell nucleus from the patient requiring a tissue transplant. The resulting embryo is then genetically matched to the patient themselves and the embryonic stem cells can be harvested and cultured to generate tissues which face little, if any, risk of rejection by the patient upon transplantation. It is possible that embryonic germ cells, found in the early germ cells which would form sperm and eggs, are pluripotent just like embryonic stem cells and may offer another route by which patient-matched cell cultures and tissues could be created. Research on both of these techniques as possible therapeutic applications is extremely limited and remains mostly theoretical however.

Approved Embryonic Stem Cell Treatments

There are no currently approved embryonic stem cell treatments although this may change in the near future as the results of the first human trials of hESCs become available. In October, 2010, the first human medical trial using hESCs commenced, with researchers investigating their potential use for spinal cord injury patients (NCT01217008). This FDA-approved clinical trial by Geron, which is now on hold as the FDA investigates possible safety concerns, was followed by an approval in late November 2010 for Advanced Cell Technology’s trial of hESC-derived retinal cells to treat patients with Stargardt’s Macular Dystrophy. This untreatable form of juvenile macular degeneration develops between 10-20yrs old and eventually leads to blindness. The same Dr. Robert Lanza who discovered how to extract embryonic stem cells without destroying the embryo is ACT’s Chief Scientific Officer and said in a press release announcing the trial that animal models had shown “100% improvement in visual performance over untreated animals without any adverse effects.” Near-normal function was achieved in these tests and the multicenter study is actively recruiting patients with Stargardt’s disease to take part in this clinical trial which remains only one of two FDA-approved hESC trials at the time of writing. At the time of writing, there are no clinical trial results demonstrating the efficacy or safety of human embryonic stem cells to treat any disease or condition and the number of induced-pluripotent adult stem cell trials currently underway may make some companies think twice before investing millions in controversial and problematic hESC research.

References

ACT Press Release: Advanced Cell Technology Receives FDA Clearance For the First Clinical Trial Using Embryonic Stem Cells to Treat Macular Degeneration, November 22nd, 2010, http://j.mp/eNtApa

Geron Corporation: Safety Study of GRNOPC1 in Spinal Cord Injury (NCT01217008), Last updated March 2011, accessed at http://j.mp/g84eQU