Using Bone Marrow Stem Cells to Reprogram Neurons and Regenerate the Retina

Spanish researchers from the Center for Genomic Regulation (CGR) have regenerated the retina in mice by reprogramming neurons with bone marrow stem cells.

Cell reprogramming normally uses genetic engineering techniques that introduces genes into cells that push them into another cell fate without taking them through an embryonic-like state. One strategy for reprogramming cells fuses those cells with other cells that express genes that drive the fused cell into a different cell fate.

Pia Cosma and her team have used cell fusion to reprogram retinal neurons in mice. The mechanism consisted of introducing bone marrow stem cells into the damaged retina. The transplanted stem cells fused with existing retinal neurons, which conveyed to these retinal neurons the ability to regenerate the retina.

“For the first time we have managed to regenerate the retina and reprogram its neurons through in vivo cell fusion. We have identified a signaling pathway that, once activated, allows the neurons to be reprogrammed through their fusion with bone marrow cells,” said Pia Cosma, who is the head of the Reprogramming and Regeneration group at the CGR and ICREA (Institució Catalana de Recerca i Estudis Avançats) research professor.

Daniela Sanges, first author or the work and postdoctoral researcher in Pia Cosma’s laboratory, said, “This discovery is important not only because of the possible medical applications for retinal regeneration but also for the possible regeneration of other nervous tissues.”

The study demonstrates that the regeneration of nervous tissue by means of cell fusion is possible in mammals and describes this new technique as a potential mechanism for the regeneration of more complex nervous tissue.

This research is in the very early stages but already there are laboratories interested in being able to continue the work and take it to a more applied level.

Daniela Sanges, Neus Romo, Giacoma Simonte, Umberto Di Vicino, Ariadna Diaz Tahoces, Eduardo Fernández, Maria Pia Cosma. Wnt/β-Catenin Signaling Triggers Neuron Reprogramming and Regeneration in the Mouse Retina . Cell Reports – 25 July 2013 (Vol. 4, Issue 2, pp. 271-286)

The eyes have it.

Amber Dance at Nature Reports Stem Cells has a very interesting article on the use of stem cell treatments to cure blindness.

Hundreds of people have had limbal stem cell transplants to treat chemical burns or diseases that scar the cornea.  Unfortunately this therapy is not commercially available to date, since acquiring data on the efficacy of such treatments is slow.  However, 60-70% of patients who have these procedures have improved vision.

This therapy is an “adult” stem cell treatment, but treatments for other types of blindness might require a more creative strategy.

Once the light passes through the transparent cornea and is bent by the lens, it hits the retina at the back of the eye.  The retina is composed of an inner neural retina that consists of photoreceptors, bipolar cells and ganglion cells that extend axons to form the optic nerve, and an outer pigmented retina into which the photoreceptors extend.  The pigmented retina secretes growth factors and clean up cell fragments from spent photoreceptor cells.  If the photoreceptors break down, then no reception of light is possible in that portion of the retina, but if the pigmented retina breaks down, then the photoreceptors will also die, since the tissue that maintains them has died.

Source: http://www.glaucoma.org/uploads/eye-anatomy-2012_650.gif

Age-related macular degeneration is the third-most common cause of blindness in the world, and it results from the death of the photoreceptors in the macula – that part of the retina where the concentration of photoreceptors are the highest and the resolution of the vision is the best.  In animals, scientists have been able to differentiate embryonic stem cells into retinal epithelial cells and transplant them into the retinas.  In rats that tend to suffer from sight degeneration, transplantation of retinal epithelial cells made from embryonic stem cells greatly slows loss of sight (R. Lund, et al., Cloning Stem Cells (2006) 8, 189-199).

Can such a treatment work?  Clinical studies suggest that it can.  In one study where ten patients were treated with fetal retinal cells, none of them experienced rejection (N. Radke, et al., Am. J. Ophthalmol. (2008) 146, 172-182).   The eye, you see, is sealed from the immune system, and there is no need to match tissue types before transplants.  However, injuries to the eye could sensitize the immune system to transplanted tissues, and a possibility might be using induced pluripotent stem cells (iPSCs).  As it turns out, differentiating embryonic stem cells into retinal epithelial cells is rather easy.  Therefore, the use of iPSCs might be quite easy.

There is reason for caution, however, because in animals the transplantation of neural stem cells into animal eyes can cause tumors (S. Arnhold, et al., Invest. Ophthalmol. Vis., (2004), 45, 4251-4255).  However, transplanted retinal epithelial cells made from embryonic stem cells have never formed teratomas.  Therefore, this cell type might not cause tumors at a high rate, and treatments with such cells might actually be feasible.