In many ways the Holy Grail in transplantation is to convert a body’s own cells into stem cells, turn those into neural cells, and then integrate them into functional circuitry within the brain. Until now, only pieces of that puzzle have been possible. Su-Chun Zhang, who was the first to convert embryonic stem cells (ESCs), and later induced pluripotent stem cells (iPSCs) into neurons, has now demonstrated that these iPSCs can be successfully introduced into the brain — in other words, he has achieved autologous (self to self), tumorless, indefinite, and functional neuro-transplantation.
Previous efforts at transplanting iPSCs in syngeneic (identical twin) animals, using teratomas (quasi-tumorous agglomerations of tissue) have largely met with failure. Zhang’s success has depended on a rigorous procedure where adult skin cells were broken down like new recruits into stem cells by genetic transformation and chemical reprogramming. They were then built back up in culture to be neural cells.
Skin cells and neural cells are both derived from precursors known as neuroectodermal cells. The cells from this lineage that go on to form the brain further differentiate into neurons, glia, and myelinating cells. After creating the precursor cells, Zhang further treated a subset of the cells to express a fluorescent protein so that they could be visualized in the new host. The cells forming the neurons were additionally biased to develop into dopamine producing cells — cells that would hopefully be restorative when introduced into the brains of Parkinson’s patients. When the fruits of their labors were observed, Zhang’s group saw that not only did these cells successfully convert to the dopaminergic lineage, they also grew neurites and integrated as regular neurons. Other neuroectodermal cells formed glial cells that serve a supporting role to the neurons.
Though the monkeys in the study have done fine for the six month trial period, the experiments are far from over. Prior to the transplantation the monkeys were chemically lesioned with a drug called MPTP to reproduce the symptoms and anatomical environment reflective of actual Parkinson’s disease. This extra step was technically not required to arrive at the experimental results reported here, but the Zhang lab intends to later demonstrate functional recovery in transplanted animals as result of having the new neural cells. At a single blow these new results chop off at the knees the ethical concerns over using ESCs, tissue rejection and immunosuppressive concerns of using foreign tissue, and the tumorigenicity of using cells radically transformed by virus or other less-defined treatments.
University of Wisconsin-Madison: Transplanted brain cells in monkeys light up personalized therapy