Sperm cells that produce insulin?

Transplantation of pancreas cells was thought to have potential for success as a new treatment for diabetes mellitus, but rejection and insulin production after transplantation have been issues. The use of induced pluripotent stem cells has also been investigated, but these reprogrammed adult stem cells have the potential for tumor development. A study from Georgetown University Medical Center conducted a proof-of-concept study utilizing spermatogonial stem cells to treat diabetics with their own stem cells. The findings that they were able to transform the sperm cells into insulin-producing pancreatic cells in vitro were presented to the 50th Annual Meeting of the American Society for Cell Biology in Philadelphia in December 2010. Read more about the diabetes study showing that sperm cells can produce natural insulin in the pancreas.

The first stem cell trial

The FDA has approved Geron's stem cell trial, the first human therapeutic trial utilizing embryonic stem cells. This first trial is to determine the viability of treating spinal cord injuries. The treatment is currently termed GRNOPC1.

 

Update: the trial was halted in 2011 after enrolling only 4 patients due to cost concerns.

Stem cells and blindness

Can stem cells cure blindness? Possibly, according to a study in Cell Stem Cell. A group at the University of Washington has found that embryonic stem cell-derived photoreceptors injected into mice with degenerative retinas results in regenerated retinal layers and increased light response.

The Mechanism of Interest

The loss or degeneration of photoreceptors in the retina, the light sensing receptors in the eye, leads to blindness. This is the mechanism seen with age-related macular degeneration, a common age-related disease. Several approaches to replacing the photoreceptors have been attempted, but a recent study in the journal Cell Stem Cell indicates that embryonic stem cells may hold the key.

Replacing Degenerative Photoreceptors

For over a decade, several types of cells have been investigated to determine their ability to regenerate the retina, leading to disappointing results. In 1998, Takashi et al. found that hippocampus-derived neural progenitor cells from adult rats could form a uniform layer in the adult rat eye, expressing markers of developing neurons. However, the cells did not eventually express retinal neuron markers, indicating incomplete retina formation.

In 2004, Klassen et al. looked at retinal progenitor cells isolated from day-old mice and found some improvement in light-mediated behavior of adults with retinal grafts, indicating that the neurons regenerated the retina to some extent. That same year, Coles et al. looked at retinal stem cells and found that they could differentiate into retinal cells. Two years later, MacLaren et al. showed that these stem cell-derived cells could be transplanted and populate a damaged eye. Also in 2006, Lamba et al. showed that embryonic stem cells could be directed to become retinal cells, including photoreceptors expressing specific markers, something the other cell types had not achieved.

The Cell Study

Lamba, Gust, and Reh at the University of Washington used mice with a mutation in their photoreceptors that mimics the vision disorder Leber’s Congenital Amaurosis. The mutant mice were injected with the embryonic stem cell-derived retinal cells developed by Lamba et al., as were normal mice, both adult and newborn. The results were different for each group of mice, depending on their needs.

The cells regenerated the retina and photoreceptors of the mutant mice and restored the light response in these mice. In normal mice, the cells simply settled and integrated into various layers of the retina, choosing to be photoreceptors more often in the adults, but without damaging the eye. The researchers are hopeful that they have found a possible treatment for photoreceptor loss. Potentially, photoreceptors can be developed from human embryonic stem cells for cell replacement therapy.

The Future of Blindness

This recent study is but one possibility for replacing damaged cells in one tissue. There are other causes of blindness that will not be affected by this treatment. Replacing the retinal cells will not help with optic nerve disorders or damage to the occipital lobe of the brain. However, clinical trials into the use of stem cell-derived photoreceptors as cell replacement therapy in macular degeneration may help millions of people in the United States alone.

References:

Coles et al. Facile isolation and the characterization of human retinal stem cells. PNAS USA, 101, 2004.

Klassen et al. Multipotent retinal progenitors express developmental markers, differentiate into retinal neurons, and preserve light-mediated behavior. Investigative Ophthalmology and Visual Science, 45, 2004.

Lamba et al. Efficient generation of retinal progenitor cells from human embryonic stem cells. PNAS USA, 103, 2006.

Lamba, Gust, and Reh. Transplantation of human embryonic stem cell-derived photoreceptors restores some visual function in Crx-deficient mice. Cell Stem Cell, 4, 2009.

MacLaren et al. Retinal repair by transplantation of photoreceptor precursors. Nature, 444, 2006.

Takashi et al. Widespread integration and survival of adult-derived neural progenitor cells in the developing optic retina. Molecular and Cellular Neurosciences, 12, 1998.

 

The UK is surpassing US research

A third British research team has received the government ok, and funding, to pursue research into hybrid embryos, one that will be half pig and half human but not contain any animal DNA. From The Scientist:

The team plans to use a new technique that, if it works, could provide a well of human embryonic stem cells without the use of human embryos. They will fuse human adult skin cells into empty pig eggs, resulting in embryos with mostly human DNA and some pig mitochondrial DNA. Then, stem cells taken from the embryos will be chemically treated to destroy the pig DNA, which could impair cell function when interacting with human mitochondrial DNA.

The team plans to use skin cells from patients with mutations for heart disease, and hopes to grow the resulting stem cells into human heart cells. The stem cells will not be used to treat humans but to research genetic mutations.

Meanwhile, New Jersey is not getting the state stem cell institute it has been building. After voters chose to not borrow state money to fund the research that would be conducted there, the state has halted construction on the $150 million facility. And though California and Massachusetts are still progressing with stem cell research, an egg shortage is making the future questionable.

Without federal funding and a viable way to obtain materials (i.e. eggs), the United States will be reading about research rather than conducting it.

Mesenchymal stem cells to treat disease

Gene Therapy had an interesting series of review articles recently on the potential of mesenchymal (adult) stem cells.

Therapeutic potential of genetically modified mesenchymal stem cells

Stem and progenitor cell-mediated tumor selective gene therapy (abstract)

Endothelial progenitor cells for cancer gene therapy (abstract)

Gene-modified bone marrow cell therapy for prostate cancer (abstract)

And for those who want a little more depth -

Inflammation and tumor microenvironments: defining the migratory itinerary of mesenchymal stem cells (abstract)

Cancer treatments would benefit greatly from targeted therapy, and developing controllable stem cell populations would such a boon for many diseases. Just think - no immune response because they are your own cells, no radiation sickness or adverse drug reactions, and no systemic damage only destruction of the targeted cell population.