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In the new research, published Sunday in the journal Nature, Studer’s team found a way to make these cells even more efficiently. This is significant in terms of ultimately testing the therapy in humans; many methods for making specific types of cells are complex and yield small amounts of the desired product.

They could scale up the process to make enough material to transplant into monkeys, whose larger brains are more akin to humans’ than other animals used in testing.

In addition, the researchers demonstrated that transplants of the cells could correct Parkinson’s-like problems in mice and rats. Three different tests of motor function “all very dramatically improved when you put the cells in,” says Studer.

While the two monkeys in the study also had brain damage reminiscent of Parkinson’s, not enough time has passed to determine whether the transplants will help, Studer says. It took five months post-transplant for the cells to have a visible effect in rodents.

The findings demonstrate the challenges of developing treatments based on living cells. “Previously, I think, many people thought of cell therapy [for Parkinson’s] as a dopamine-producing biological pump,” says Ole Isacson, a neuroscientist at Harvard Medical School. But in reality, it requires a very specific replacement of nerve cells. Unless you have a specific differentiation protocol, you won’t get functional recovery in rodent models.” Isacson was not involved in the research but has collaborated with Studer on other projects.

Researchers mostly used embryonic stem cells in these experiments, because tissue derived from these cells is already being used in human trials for treating spinal cord injury and certain types of blindness. They also showed that the protocol works on induced pluripotent stem (iPS) cells, which are derived from adult cells that are turned back to an embryonic-like state using a combination of genetic or chemical factors. iPS cells are genetically matched to the cell donor, and might ultimately provide a preferable source of tissue for therapy. However, these cells are further from human testing because they are much less studied than embryonic cells.

Studer’s team now plans to make the cells on an even larger scale in a facility that meets conditions set by the U.S. Food and Drug Administration for human therapies. “We need to be able make enough cells to graft 100 patients,” says Studer. He predicts that will take a year or two, followed by extensive safety testing to make sure the differentiated cells do not behave in unexpected ways once implanted.  

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Credit: Nature

Tagged: Biomedicine, Materials, stem cells, Parkinson's

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