Advanced iPS technology to cure retinal degenerative diseases and restore visual function
Visual impairment is a big medical and public health problem that might be combated thanks to recent breakthrough in iPS technology to correct gene defect responsible for a blinding disorder in generated iPS produced from the patient’s own skin. By Dr. Pavlica.
Nowadays diseases such as retinitis pigmentosa, dry age-related macular degeneration and diabetic retinopathy are the leading causes of incurable blindness affecting millions people around the world. Ophthalmologists are searching for future therapies that might help patients who have little or no hope for improved or saved sight or vision, due to death of photoreceptor cells (rods and cones) located in the retina. The retina is a very thin layer of light-sensitive neural tissue lining at the back of the eyeball. Every cell in the body “stems” from a cell: stem cell.
The advances in the stem cell field and their potential use for cell-based delivery in the eye presents a technical challenge to achieve a better treatment for blindness prevention. In particular, stem cell therapy has advantage over traditional therapies to cure diseased retina since the patient gets rid of the disease without any kind of surgery or any other painful method having no side effects.
Induced pluripotent stem cells (iPSC or iPS) are artificially reprogrammed adult somatic cells (usually skin cell) by inducing a “forced” expression of specific genes. Because iPSCs are developed from a patient’s own somatic cells, they offer the opportunity for autologous cell transplantation. Since its discovery in mouse in 2006 and in human in 2007, iPS technology takes a hit revolutionizing stem cell biology and modern medicine. Besides to regenerative medicine, they have big potential in disease modelling and drug screening.
In the past five years, vision scientists have been exploring ways to use this new technology to reverse blindness. Like embryonic stem cells, iPSCs have the ability to become any other cell in the body, but are devoid of ethical, emotional and political issues usually associated with the use of tissue derived from human embryos. Theoretically, they have the capacity to generate living human beings, hence posing a moral dilemma that might arise ethical concerns.
A team of stem cell researchers from University of Wisconsin-Madison reported for the first time the functional correction of disease-specific iPS cells derived from a human patient with an uncommon inherited eye disease (gyrate atrophy) using both pharmacologic (vitamin B6 supplement) and genetic approach. The results of their study, published in Stem Cells this month, hold great promise for future therapies to reverse blindness and cure retinal degenerative diseases that affect millions worldwide (Meyer et al. Stem Cells, 2011; DOI: 10.1002/stem.674).
For sure, described method for production of highly enriched populations of physiologically active retinal cell types from hiPS provides a platform for in vitro investigation of patient-specific drug effects, gene repair strategies and disease mechanisms. However, investigators should beware when extrapolating data obtained from cell culture systems to whole organisms. Unfortunately, tendency for tumor formation after iPSC transplantation and the low efficiency of the technology are still unresolved problem within iPS. Their use in clinical settings is yet not safe due to recent discoveries of frequent genetic aberrations found in iPS after reprogramming and extended culture. Researchers strive continuously to improve their techniques for production and differentiation of iPS. Bioreactors technology may be used to enable improved differentiation and enhanced quantity of transplantable cells.
Finally, we should emphasize that it is still unresolved which cell type is the most beneficial for treatment of diseased retina (embryonic stem cells, neural stem cells, retinal progenitors, bone marrow-deived stem cells or iPS). In contrast to embryonic stem cells, iPS and neural stem cells, we can collect BMSCs without encountering any ethical problem and expand easily in a large scale for auto transplantation without risk for carcinogenesis. Hence, “old good” multipotent BMSCs constitute still a strong and hopeful candidate for therapy and regeneration of diseased retina.
They are also perspective and promising tools for the upcoming decade of personalized medicine where the patient´s own cells-differentiated into appropriate cell types-will be used to treat their condition without ethical, cancer or mutation- causing concerns. However, constantly evolving technologies for generation of iPSC lines promise to revolutionize the field of (personalized) medicine offering new hope for our understanding and treatment of many diseases as well as for high throughput drug discovery and screening.
By Dr. Pavlica, scientist leader in biotechnology research at the University of Leipzig, Germany, and member of the European Medical Writers Association (EMWA).