Researchers have for the first time successfully converted adult human skin cells into neurons of the type that regulate appetite, an advance that may lead to new treatments for obesity.
The study, led by researchers at Columbia University Medical Center (CUMC) and the New York Stem Cell Foundation (NYSCF), provides a patient-specific model for studying the neurophysiology of weight control.
"Mice are a good model for studying obesity in humans, but it would be better to have human cells for testing," said senior author Rudolph L Leibel, co-director of the Naomi Berrie Diabetes Center at CUMC.
"Unfortunately, the cells that regulate appetite are located in an inaccessible part of the brain, the hypothalamus.
"So, until now, we've had to make do with a mouse model or with human cells harvested at autopsy. This has greatly limited our ability to study fundamental aspects of human obesity," Leibel said.
To make the neurons, human skin cells were first genetically reprogrammed to become induced pluripotent stem (iPS) cells.
Like natural stem cells, iPS cells are capable of developing into any kind of adult cell when given a specific set of molecular signals in a specific order.
The iPS cell technology has been used to create a variety of adult human cell types, including insulin-producing beta cells and forebrain and motor neurons.
"But until now, no one has been able to figure out how to convert human iPS cells into hypothalamic neurons," said co-author Dieter Egli, assistant professor of pediatrics and a senior research fellow at NYSCF.
The CUMC/NYSCF team determined which signals are needed to transform iPS cells into arcuate hypothalamic neurons, a neuron subtype that regulates appetite. The transformation process took about 30 days.
The neurons were found to display key functional properties of mouse arcuate hypothalamic neurons, including the ability to accurately process and secrete specific neuropeptides and to respond to metabolic signals such as insulin and leptin.
"We don't think that these neurons are identical to natural hypothalamic neurons, but they are close and will still be useful for studying the neurophysiology of weight control, as well as molecular abnormalities that lead to obesity," said Leibel.
"In addition, the cells will allow us to evaluate potential obesity drugs in a way never before possible," he said.
The study was published in the Journal of Clinical Investigation.
