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Stem Cell Application

Stem cells have the unique characteristics of self-renewal and the capability of differentiating into other cell types. iPS cells can evade ethical concerns and potential allogeneic rejection. These characteristics are appealing for therapeutic uses such as cell therapy for leukemia, autoimmune disease and, recently, even to cure blindness.

Eyes are complex organs and comprised of many types of cells with specific roles. Together, these cells form a system to detect light from the environment and transfer this information to the brain. The retinal pigment epithelium (RPE) is the cell layer responsible for the conversion of light waves into a cell signal.

Image representing the different steps when treating retinal diseases with iPS cells. There is a person's silhouette and an arrow pointing toward a group of cells. Those cells are cultured and pluripotency factors are added. Another arrow points to show that the cells have become i P S cells. There is a selection of i P S cells so they can be cultured again and differentiated into retinal pigment epithelial cells. An arrow pointing from this second culture to a syringe, showing that these R P E cells are isolated and injected under patient's retina. A final arrow points to an illustration of a human eye.

Figure 1. Treatment of retinal diseases with iPS cells. Somatic cells are cultured and reprogrammed into iPS cells by the addition of pluripotency factors (A). Once those cells are differentiated into RPE cells, they are tested and injected under the patient’s retina (B).

The RPE is comprised of a monolayer of pigmented cells made up of apical membranes composed of light-sensitive outer segments of photoreceptors, and a basolateral membrane facing the fenestrated capillaries of the choroid.

The RPE cells are paramount in maintaining the structure and function of the retina and photoreceptors. RPE cells are also important for processing nutrients that supplement the retina. RPE cells can be damaged by a variety of diseases, such as age-related macular degeneration (AMD), retinitis pigmentosa, Stargardt’s disease and Leber's congenital neurosis. Progressive damage of the RPE can lead to eye dysfunction and even blindness.

RPE donors are rare and difficult to find; current studies are attempting to use iPS to generate RPE cells for eye transplants, and human clinical trials of RPE transplants began in 2014. Currently, treatment is being performed by injecting 150 microliters of RPE cells under a patient’s retina.

References:

  • Cyranoski, D. (2014). Japanese woman is first recipient of next-generation stem cells. Nature, 12.
  • Pagliuca, F. W., Millman, J. R., Gürtler, M., Segel, M., Van Dervort, A., Ryu, J. H., ... & Melton, D. A. (2014). Generation of functional human pancreatic β cells in vitro. Cell, 159(2), 428-439.