Direct reprogramming in vitro and in vivo is a hot topic today. We named it “The Method of the Year 2010 and 2012“. There are many discussions about potential advantages and therapeutic value of this technique. However, more rigorous tests should be done in animals in order to move forward. Importantly, directly reprogrammed cells in vitro should be tested for their functionality in in vivo models. If reprogramming is real and has any therapeutic value, converted cells should:
- persist long-term in tissues;
- integrate into tissue structurally and functionally;
- differentiate or/and maintain benign stable phenotype.
These rigorous assays were recently done for induced Induced Neural Stem Cells (iNSC), directly reprogrammed in vitro from skin fibroblasts.
… we investigated the characteristics of mouse-fibroblast-derived iNSCs 6 months after transplantation into adult mouse brains. We show that iNSCs differentiate into neurons, astrocytes, and oligodendrocytes in vivo. These cells survived for long periods in the mouse brain and functionally integrated into the existing neuronal circuitry. These results provide strong evidence that this iNSC procedure might be a valuable tool for cell-replacement therapies.
Good cell survival at six months without tumorigenesis is much wanted result! Importantly, iNSC lost their “stem cell identity” after transplantation into the brain, but retained ability to differentiate into 3 neural lineages. I’d like to see longer observation in large animals, for example 3-5 years in monkeys.
Significant part of the study was dedicated to measuring functional integration of iNSC into the brain. The authors showed integration by formation of synapses and electrophysiological tests. This study sets a good example of how functionality of reprogrammed in vitro cells could be tested. Unfortunately, therapeutic value of integrated iNSC was not tested in this study.
Very interesting discussion about this study took place in social platform Reddit. It yielded more than 200 comments in few days! Among some noise you can find really thoughtful comments about defining “functional neural integration” and “neural networks”. I’d highly recommend you to read this article and look at comments on Reddit!