Adult Stem Cell Therapeutics in Diabetic Retinopathy

Diabetic retinopathy (DR), a complication of diabetes, is one of the leading causes of blindness in working-age adults. The pathology of the disease prevents the endogenous stem cells from participating in the natural repair of the diseased retina. Current treatments, specifically stem cell therapeutics, have shown variable efficacy in preclinical models due to the multi-faceted nature of the disease. Among the various adult stem cells, mesenchymal stem cells, especially those derived from adipose tissue and bone marrow, have been explored as a possible treatment for DR. This review summarizes the current literature around the various adult stem cell treatments for the disease and outlines the benefits and limitations of the therapeutics that are being explored in the field. The paracrine nature of adipose stem cells, in particular, has been highlighted as a potential solution to the lack of a homing and conducive environment that poses a challenge to the implantation of exogenous stem cells in the target tissue. Various methods of mesenchymal stem cell priming to adapt to a hostile retinal microenvironment have been discussed. Current clinical trials and potential safety concerns have been examined, and the future directions of stem cell therapeutics in DR have also been contemplated.

iPS-Cell Technology and the Problem of Genetic Instability—Can It Ever Be Safe for Clinical Use?

The use of induced Pluripotent Stem Cells (iPSC) as a source of autologous tissues shows great promise in regenerative medicine. Nevertheless, several major challenges remain to be addressed before iPSC-derived cells can be used in therapy, and experience of their clinical use is extremely limited. In this review, the factors affecting the safe translation of iPSC to the clinic are considered, together with an account of efforts being made to overcome these issues. The review draws upon experiences with pluripotent stem-cell therapeutics, including clinical trials involving human embryonic stem cells and the widely transplanted mesenchymal stem cells. The discussion covers concerns relating to: (i) the reprogramming process; (ii) the detection and removal of incompletely differentiated and pluripotent cells from the resulting medicinal products; and (iii) genomic and epigenetic changes, and the evolutionary and selective processes occurring during culture expansion, associated with production of iPSC-therapeutics. In addition, (iv) methods for the practical culture-at-scale and standardization required for routine clinical use are considered. Finally, (v) the potential of iPSC in the treatment of human disease is evaluated in the light of what is known about the reprogramming process, the behavior of cells in culture, and the performance of iPSC in pre-clinical studies.

Enhancement of FUS Mediated Delivery of Stem Cells to Brain

We propose that magnetic targeting of super-paramagnetic iron oxide nanoparticles (SPION) labeled cells will enhance the delivery of stem cells to brain after focused ultrasound (FUS) mediated opening of the blood-brain barrier (BBB). FUS mediated opening of the BBB allowing stem cells to enter the brain from the blood is a remarkable advance in delivery of stem cell therapeutics over current invasive methods of brain injection. However the efficiency of cellular entry is low. SPIONs are taken up by stem cells, allowing for labeling of transplanted stem cells in brain both with histology and MRI. Our research shows that SPION labeled stem cells show enhanced brain retention near a magnet on the skull, in a rat model of traumatic brain injury. There is no experience combining these two minimally invasive strategies to deliver stem cells to the brain. We will assess the capacity of an external magnet to enhance the efficiency of delivery to brain of SPION loaded stem cells after transient opening of the BBB using FUS. We will evaluate SPION loaded neural stem cells delivered by intravenous infusion in rats that have undergone MRI targeted FUS opening of the BBB along with a magnet placed over the skull of the sonicated hemisphere, to animals with FUS alone. The number and distribution of stem cells will be quantitative for each group to assess enhancement of delivery of stem cells after BBB opening using FUS by the addition of SPION loading and an external magnet.