Neural Cells Made from Monkey Skin Cells Integrate into Monkey Brains and Form Neurons

Stem cell scientists from the University of Wisconsin at Madison have transplanted neural cells that were made from a monkey’s skin cells into the brain of that same monkey. The transplanted cells formed variety of new brain cells that were entirely normal after six months.

This experiment is a proof-of-principle investigation that shows that personalized medicine in which regenerative treatments are designed for specific individuals is possible. These neural cells were derived from the monkey’s skin cells and were, therefore, no foreign. Therefore, there is no risk of them being rejected by the host immune system.

Su-Chun Zhang, professor of neuroscience at the University of Wisconsin-Madison, said: “When you look at the brain, you cannot tell that it is a graft. Structurally the host brain looks like a normal brain; the graft can only be seen under the fluorescent microscope.”

Marina Emborg, associate professor of medical physics at UW-Madison and one of the lead co-authors of the study, said: “This is the first time I saw, in a nonhuman primate, that the transplanted cells were so well-integrated, with such a minimal reaction. And after six months, to see no scar, that was the best part.”

The skin-derived neural cells were implanted into the monkey brain by means of a state-of-the-art surgical procedure whereby the surgeon was guided by a live MRI. The three rhesus monkeys used in the study at the Wisconsin National Primate Research Center had brain lesions that caused Parkinson’s disease. Up to one million Americans suffer from Parkinson’s disease, and some 60,000 new patients are diagnosed with it each year. Parkinson’s disease results from the death of midbrain neurons that manufacture the neurotransmitter dopamine.

The cells that were transplanted into the brain were derived from induced pluripotent stem cells (iPSCs), which, like embryonic stem cells, can develop into virtually any cell in the adult human body.

Once the iPSC lines were established, Zhang and his colleagues differentiated them into neural progenitor cells (NPCs), which have the ability to form a wide variety of brain-specific cells. Zhang was the first scientist to ever successfully differentiate iPSCs into NPCs, and therefore, this paper utilized his unique expertise.

According to Zhang, “We differentiate the stem cells only into neural cells. It would not work to transplant a cell population contaminated by non-neural cells. By taking cells from the animal and returning them in a new form to the same animal, this is a first step toward personalized medicine. Now we want to more ahead and see if this leads to a real treatment for this awful disease.”

Another positive sign was the absence of any signs of cancer, which is a troubling but potential outcome of stem cell transplants. Zhang jubilantly but guardedly announced that the appearance of the cells is “normal, and we also used antibodies that mark cells that are dividing rapidly, as cancer cells are, and we do not see that. And when you look at what the cells have become, the become neurons with long axons, as we’d expect. The also build oligodendrocytes that are helping build insulating sheaths for neurons, as they should. That means they have matured correctly, and are not cancerous.”

Zhang and his colleagues at the Waisman Center on the UW-Madison campus designed this experiment as a proof of principle investigation, but because they did not transplant enough dopamine-making cells into the brain, the animal’s behavior did not improve. Thus, although this transplant technique is certainly very promising, it is some ways from the clinic.

As noted by Emborg: “Unfortunately, this technique cannot be used to help patients until a number of questions are answered: Can this technique improve the symptoms? Is it safe? Six months is not long enough.” Emborg continued, “And what are the side effects? You may improve some symptoms, but if that leads to something else, then you have not solved the problem.”

Regardless of these shortcomings, this study still represents a genuine breakthrough. “By taking cells from the animal and returning them in a new form to the same animal, this is a first step toward personalized medicine,” said Emborg.