Neurologist Ole Isacson and his Harvard Medical School team successfully implanted neurons made from a monkey’s own cells to treat Parkinson’s disease in those animals. The implanted neurons were watched for two years, and they proved to be both safe and effect in the treatment of Parkinson’s disease.
Induced pluripotent stem cells or iPSCs are made from mature, adult cells by means of a combination of genetic engineering and cell culture techniques. The cells resemble embryonic stem cells in many of their growth characteristics and gene expression patterns, but they are have several differences as well. One of the biggest differences between iPSCs and embryonic stem cells is that the reprogramming process that makes iPSCs places cells under stresses that increase the mutation rate and makes iPSCs, on average, more likely to cause tumors than embryonic stem cells. However, it is also clear that not all iPSC lines are the same and careful screen protocols that determine safe lines from less safe lines.
A distinct advantage of iPSCs over embryonic stem cells is that they have the same set of cell surface proteins as the patient from whom they were made, which makes them less likely to be rejected by the patient’s immune system. Even though some experiments had shown that cells derived from iPSCs can be rejected by the patient’s immune system, these experiments used poor-quality iPSC lines. High-quality iPSCs lines are much less likely to be rejected by the immune system. Therefore, using a patient’s own stem cells has distinct advantages as opposed to embryonic stem cells.
Isacson and his colleagues made patient-specific iPSCs from cynomolgus monkeys and used them to produce midbrain dopamine-making neurons – the kind that die off in patients with Parkinson’s disease – and used them to treat those same monkeys that suffered from Parkinson’s disease.
Such an experiment is potentially risky because even though differentiation of pluripotent stem cells into midbrain dopamine-making neurons is feasible, getting pure cultures of these cells that do not have any non-differentiated cells that can cause tumors is not all that easy to do. Fortunately, some advances in these techniques in the past few years have increased the ability of laboratories to not only produce large quantities of midbrain dopamine-making neurons, but screen them properly before transplantation.
In this experiment, Isacson and his team analyzed their implants for up to 2 years. The implanted animals were subjected to routine observations and tests, and in one animal, with the most successful protocol, they observed that lateral engraftment of CM-iPSCs on one side of the animal’s brain produced a gradual onset of functional motor improvement on the side opposite to the that of dopamine neuron transplantation, and increased motor activity. These implantation also did not require any immunosuppression and the implants caused to evidence of graft rejection. Postmortem analyses of these implanted animals revealed robust survival of midbrain-like dopaminergic neurons and extensive outgrowth into the tissue into which the cells were transplanted; the putamen, which is one of the “basal ganglia” that help control voluntary movements.
This remarkable proof-of-concept experiment supports further development of iPSC-derived cell transplantation for treatment of Parkinson’s Disease.