Fat Cells Transformed To Resemble Nerve Cells

During the past several years, Duke researchers and scientists from Artecel demonstrated the ability to reprogram adult stem cells taken from human liposuction procedures into fat, cartilage and bone cells. All of these cells arise from mesenchymal, or connective tissue, parentage. However, the latest experiments have demonstrated that researchers can transform these stem cells from fat into a totally different lineage, that of neuronal cells.

Although it is unclear at this point whether or not the new cells will function like native nerve cells, the researchers are optimistic that if future experiments are as successful as the ones to date, these new cells have the potential to treat central nervous system diseases and disorders.

"These experiments are proof of principle that it is possible to change one lineage of adult stem cells into another using fat," said Duke's Henry Rice, M.D., pediatric surgeon and senior author of the paper published today (May 31, 2002) in the journal Biochemical and Biophysical Research Communications (BBRC), a journal that publishes fast-breaking research in experimental biology. "If future studies in animal models are successful, we'll have gone a long way toward demonstrating the power of these cells to treat human diseases."

The research was supported by the American College of Surgeons and Artecel Sciences in Durham. Rice is a consultant for Artecel Sciences.

The team conducted parallel experiments in mice and human cells. In both cases, mouse adipose (fat) cells and fat cells taken from human liposuction procedures were treated with chemicals and growth factors and allowed to grow in the laboratory.

"Within hours the treated cells in both models began to look like neuronal cells and began to produce measurable amounts of proteins normally expressed by nerve cells," Rice said.

"This is a promising first step in the use of an abundant source of adult stem cells in the setting of central nervous system repair," said Jeffrey Gimble, M.D., chief scientific office at Artecel and co-author of the BBRC paper. "While it is known that you can create neuronal cells from adult stem cells taken from bone marrow, we feel that our approach with fat offers a limitless supply of readily obtainable adult stem cells."

Until recently, it was believed that organisms were born with the full complement of neuronal cells, and that new neurons could not be formed. According to the scientists, their research, as well as the experiments performed by others on bone marrow stem cells, open up new possibilities for the treatment of nervous system disorders or injuries.

"We are trying to think about human disease in a new way," Gimble said. "Everyone is used to the concept of surgical, medical or pharmacological approaches to the treatment of disease -- we're looking at one of the next steps in biotechnology, which is using cellular therapies."

The researchers are quick to point out that there are still many hurdles to be overcome before the use of these cells can occur in a clinical setting.

First, the cells were grown in tissue culture and survived after neuronal differentiation for several days. The researchers are confident that as they refine their techniques and evaluate different growth factors, they can extend the lifespan of these cells.

Secondly, while the new nerve cells have a form and function that resemble native nerve cells, it is not known if they will function in the same way as native nerve cells. The next series of experiments in the mouse model will test how the new cells react in a living system and if they will function like nerve cells, the researchers say.

The researchers believe the first animal models will focus on acute injuries such as stroke, in which blocked blood flow to the brain causes brain cell death, and spinal cord injuries. Other members of the team are, from Duke, Kristine Safford and Shawn Safford, M.D., and from Artecel Sciences, Kevin Hicok, Ph.D., Yuan-Di Halvorsen, Ph.D., and William Wilkison, Ph.D.