Jens Schwamborn and Kathrin Hemmer from the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg have shown that implanted neurons made from induced pluripotent stem cells show long-term stability in the brain.
Induced pluripotent stem cells (iPSCs) are made from mature adult cells by means of genetic engineering and cell culture techniques. These cells have embryonic stem cell-like capacities and can, potentially differentiate into any adult cell type. Because neurons made from iPSCs have sometimes not shown instability, the ability of neurons derived from iPSCs to stably integrate into brain has been questioned.
Schwamborn and Hemmer showed that six months after implantation, their iPSCs-derived neurons had become fully functionally integrated into the brain. This successful integration of iPSC-derived neurons into lastingly stable implants raises hope for future therapies that will replace sick neurons with healthy ones in the brains of patients with Parkinson’s disease, Alzheimer’s disease and Huntington’s chorea, for example. This work was published in the current issue of Stem Cell Reports.
The LCSB research group hopes to bring cell replacement therapy to maturity as a treatment for neurodegenerative diseases. The replacement of sick and/or dead neurons in the brain could one day cure disorders such as Parkinson’s disease. However, devising a successful therapy in human is a long, arduous process, and for good reasons. “Successes in human therapy are still a long way off, but I am sure successful cell replacement therapies will exist in future. Our research results have taken us a step further in this direction,” declared Schwamborn.
In their latest tests, the LCSB research group, in collaboration with colleagues from the Max Planck Institute and the University Hospital Münster and the University of Bielefeld, made stable neuronal implants in the brain from neurons that were derived from reprogrammed skin cells. They used a newer technique in which the neurons were produced from neural stem cells (NSCs). These NSCs or induced neural stem cells (iNSCs) had, in turn been made from iPSCs that were made from the host animal’s own skin cells, which considerably improves the compatibility of the implanted cells. Mice who received the neuronal implants showed no adverse side effects even six months after implantation. The new neurons were implanted into the hippocampus and cortex regions of the brain. Implanted neurons were fully integrated into the complex network of the brain and they exhibited normal activity and were connected to the original brain cells via newly formed connections known as synapses, which are the contact points between nerve cells.
These tests demonstrate that stem cells researchers are continuing to get a better handle on how to use cells derived from something other than human embryos in order to successfully replace damaged or dead tissue. “Building upon the current insights, we will now be looking specifically at the type of neurons that die off in the brain of Parkinson’s patients – namely the dopamine-producing neurons,” Schwamborn reports.
In future experiments, implanted neurons could provide the neurotransmitter dopamine (which is lacking in patients with Parkinson’s disease) directly into the patient’s brain and transport it to the appropriate sites. Such a result would herald an actual cure for the disease rather than a short-term fix. The first trials in mice are in progress at the LCSB laboratories on the university campus Belval.