Tiny scaffolding allows stem cells to become working fat cells

03/22/05



Fat cells of mouse subcutaneous tissue. Below, tissue engineered fat cells from pre-adipocytes. Images courtesy of Professor Douglas Kniss. Click here for a high resolution photograph.

COLUMBUS, Ohio -- Researchers here have used a new microscopic, three-dimensional scaffolding to coax mouse stem cells to transform themselves into fat cells, and then to function identical to how fat cells naturally do in the body.

While other studies have previously grown fat cells, or adipocytes, in the laboratory, those cells never completely functioned in the same way they do in normal tissue. They failed to produce the genetic and biologic components that all cells require to do their work.

This discovery offers hope of a new approach to growing fat tissue for use in breast reconstruction surgery and other clinical needs, and may even be important for curing type II diabetes.

Douglas Kniss, professor of obstetrics and gynecology and of biomedical engineering at Ohio State University, reported this progress in the current issue of the journal Tissue Engineering.

"There is a serious shortage of transplantable organs available for thousands of patients nationally," Kniss said. "One ultimate goal of this work might be creating new tissue that could serve either as a temporary substitute while waiting for a donor organ, or even providing a replacement organ."

Along with Xihai Kang and Yubing Xie, both postdoctoral fellows in his laboratory, Kniss built a fabric-like carpet of polyethylene terephathalene (PET), or Dacron, fibers that served as scaffolding upon which new fat cells were grown.

In conventional cell cultures, cells usually grow as flat deposits bathed in growth medium. While useful, these "two-dimensional" patches fail to mimic all the tasks performed by cells in vivo. Specific genes, proteins and hormones normally produced by healthy cells are often absent in two-dimensional colonies.

"The PET fibers are spun out onto a mat that resembles the intracellular matrix that bonds cells together in normal tissue. The fibers are about the size of a collagen fiber, several nanometers (a billionth of a meter) across, and provide tensile strength to support the growing tissue," Kniss said.



Click here for a high resolution photograph.

The researchers then "seeded" that scaffolding with cells called pre-adipocytes cells that had begun their transformation from stem cells. "They just needed to be tweaked with a cocktail of hormones for them to evolve into fat cells," he said.

Kniss said that the transformation into bona fide fat cells took about two weeks to complete. At that point, the cells were able to absorb lipids a hallmark task of fat cells.

Researchers were able to extract RNA from the cells, just as they can from naturally occurring fat cells, and from that proved that the cells expressed the normally expected array of genes, and subsequent proteins and did so as well as occurs in normal tissue. So far, the researchers have kept the cells alive and thriving for several months and hope to maintain them for up to a year.

"We know that the environment in which a community of cells finds itself has a great deal of influence on the biology underway within those cells," Kniss said. "And that biology is always translated into changes in gene expression and assemblies of proteins." That is why the three-dimensional scaffolding for cell growth in the laboratory is so important.

The researchers' focus on fat cells as a test bed for this approach to cell growth offers important medical potential. While experts once thought a persons number of fat cells was set at birth, they now know individuals can either lose existing fat cells or grow new ones. And aside from the implications for dieting and obesity, a person's population of fat cells has other vital roles.

Fat cells extract lipids, or fatty acids, from the bloodstream. They also become a huge reservoir for glucose as well, and play a role in insulins ability to effectively convert glucose into energy.

"If we could learn how to control fat formation in the body, then we could keep people leaner, lowering their chances of becoming insulin-dependent, and lowering the likelihood they would develop type II diabetes," Kniss said.

He also suggested that the new approach might have commercial applications as a way of testing new drugs. "Small, three-dimensional cell colonies could be grown on multi-well assay plates and be used to test dozens of compounds at the same time," he explained.

"Since these cells better resemble how cells function in living tissue, they would offer a better test than current two-dimensional cell colonies provide." Kniss is currently working with an Ohio company to consider research on such new assay devices.

Source: Eurekalert & others

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