Reverse Engineered Stem Cells to be used in Parkinson's Disease Clinical Trial

The technical term for reverse engineered somatic cells is known as induced Pluripotent Stem Cells (iPSC's). These cells are reprogrammed through genetic manipulation that reverses them into a Pluripotent stem cell. A pluripotent stem cell is formed in later stages of embryonic development, however is capable of giving rise to most of the cell types. Since, iPSCs are engineered from body tissues, they are considered as a more ethical substitute for sourcing stem cells.

How was the First iPSC Engineered?

The process of iPSC Engineering. Image: University of Utah

Induced pluripotent stem cells (iPSC's) are first isolated from the patient and multiplied in a petri dish. Mostly, fibroblasts are used for this purpose because they have more genetic elasticity. Next the cells are exposed to reprogramming factors that are four transcription factors, namely: Oct4, Sox2, cMyc and Klf4. For this purpose attenuated viruses carrying the target genes are used to 'infect' the fibroblasts that effectively incorporate these external genes into the cellular DNA. After a few weeks the cells are completely transformed into their precursor pluripotent stem cells. These iPSC's serve as a basis for production of different cell types.

How were iPSC's used in a Parkinson's Disease Model?

Parkinson's is characterized by the loss of dopaminergic neurons of the midbrain. The iPSC's were used to generate dopaminergic neurons and successfully implanted in the midbrains of primate models of Parkinson's. Not only did the cells survive grafting but were also able to develop connections and restore lost brain function. These cells also did not produce any significant immune response. This study was originally performed by a Japanese team of scientists in 2017.

The next step is to translate these successful results in to a human clinical trial. The clinical trial is set to use iPSC's derived from the patients, maturing them into dopaminergic neurons and grafting them into the midbrain region.

The prospects of this type of study are mostly bright, because stem cells are harvested from the patient themselves this would translate into a very slim chance of graft rejection. Secondly, iPSC's have proven to be useful in the past where they have been successfully used to treat macular degeneration and myocardial disorders.