Pluripotent stem cells repair the retina
Johns Hopkins University researchers working under the guidance of Dr. Elias Zambidis have developed a method for producing human induced pluripotent stem cells (iPSCs) capable of repairing retinal vascular damage in mice. As precursors of iPSCs, the authors used cord blood stem cells transformed into a pluripotent state without the use of viral vectors associated with the risk of mutations and subsequent cell malignancy.
Umbilical cord blood stem cells were chosen by the authors as the source material for several reasons. In addition to the ease of obtaining the cells themselves, their DNA contains virtually no acquired mutations and epigenetic memory.
To return these cells to the state corresponding to the state of the cells of a 6-day-old embryo, the authors used not traditional viral vectors–carriers of transforming genes, but plasmids - ring DNA molecules that rapidly replicate inside the cell and then degrade.
The obtained iPSCs were cultured in an environment conducive to their differentiation into vascular progenitor cells. After that, cells expressing the surface proteins CD31 and CD146, which are markers of vascular endothelial cells, were selected from the resulting population using the method of cell sorting with activated fluorescence (fluorescent sorting). According to the authors, this method allowed to obtain twice as many vascular progenitor cells as the traditional method of differentiation of iPSCs, the precursors of which are keratinocytes of the skin. More importantly, the cells obtained using the new method showed higher levels of expression of markers of immature vascular epithelial cells, were less prone to entering the phase of physiological aging and less sensitive to DNA-damaging factors. At the same time, their DNA contained fewer reprogramming errors transmitted during division.
The isolated cell population was injected into three groups of immunodeficient mice with retinal lesions. One group was injected directly into the eye, the second – into the sinus sinus located in the immediate vicinity of the eye, and the third – into the caudal vein. Retinal images of animals obtained 45 days after the procedure showed that, regardless of the injection site, iPSCs integrated into the damaged tissue and restored blood vessels.
Vascular stem cells formed from iPSCs (white arrow),
integrating into the damaged retinal vessel and restoring it.
The authors plan to conduct additional experiments on a rat model of diabetes, in which retinal vascular damage is more comparable to what is happening in the human retina than the mouse model involved in this study.
Zambidis notes that he often shares his iPSCs obtained from umbilical cord blood cells with other research groups. He also believes that the popular belief that therapeutic iPSCs should be specific to each patient is partly erroneous. As confirmation, he gives an example of the success of partially compatible bone marrow transplantation, the effectiveness of which is comparable to the effectiveness of fully compatible transplants.
He also believes that large banks of iPSCs have a great future, providing access to these cells to researchers around the world. The creation of such structures requires huge costs, however, Japanese specialists under the leadership of the pioneer in the field of iPSC Shinya Yamanaka are already creating a bank of iPSCs obtained from cord blood cells stored in Japanese cryobanks.
Article by T. S. Park et al. Vascular Progenitors from Cord Blood-Derived iPSC Possess Augmented Capacity for Regenerating Ischemic Retinal Vasculature is published in the journal Circulation.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on Johns Hopkins Medicine:
Lab-Grown, Virus-Free Stem Cells Repair Retinal Tissue in Mice.
29.01.2014